1,926 results on '"M Hirai"'
Search Results
2. Exertional oscillatory ventilation in subjects without heart failure reporting chronic dyspnoea
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J. Alberto Neder, Alcides Rocha, Flavio F. Arbex, Maria Clara N. Alencar, Priscila A. Sperandio, Daniel M. Hirai, and Danilo C. Berton
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Pulmonary and Respiratory Medicine - Published
- 2022
3. Ion irradiation effects on FeCrAl-ODS ferritic steel
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K. Kondo, S. Aoki, S. Yamashita, S. Ukai, K. Sakamoto, M. Hirai, and A. Kimura
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Nuclear engineering. Atomic power ,TK9001-9401 - Abstract
The correlation between microstructure and mechanical property of ion irradiated 12Cr-6Al ODS ferritic steel was studied. Ion irradiation experiments were performed using 10.5 MeV Fe ions up to the nominal displacement damage of 20 dpa with the damage rate of 1 × 10−4 dpa/s, while the irradiation temperature was 300 °C. Oxide nanoparticles showed stable size distribution and mean size under ion irradiation up to 20 dpa. The irradiation microstructure examined by TEM revealed that the mean size and number densities of irradiation-induced defect clusters increased with the displacement damage. The correlation between irradiation microstructure and radiation hardening was theoretically calculated using the dispersed barrier hardening model. The results showed a good agreement with the experimentally measured hardness data up to irradiation at 5 dpa, while a slight discrepancy was found between theoretical and experimental hardness values under irradiation at 20 dpa. Radiation hardening in 12Cr-6Al ODS ferritic steel was mainly caused by irradiation-induced defect clusters below the irradiation dose of 5 dpa. As the irradiation dose increased toward 20 dpa, an additional influence of the radiation appeared, which was assumed to be induced by α’ phase transformation.
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- 2018
- Full Text
- View/download PDF
4. Electroluminescence Characteristics of Epoxy/TiO2 Nanocomposites
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M. Hirai, M. Kurimoto, K. Tohyama, T. Sawada, S. Yoshida, T. Umemoto, and H. Muto
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- 2022
5. Assimilating Passive Microwave Brightness Temperature Data into a Land Surface Model to Improve the Snow Depth Predictability.
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Tobias Graf, Toshio Koike, Xin Li 0029, M. Hirai, and Hiroyuki Tsutsui
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- 2006
- Full Text
- View/download PDF
6. Effects of inorganic nitrate supplementation on cardiovascular function and exercise tolerance in heart failure
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Scott K. Ferguson, Daniel M. Hirai, Michael D. Belbis, Michael J. Holmes, Jason D. Allen, Eddie Weitzberg, Mary N. Woessner, and Mattias Carlström
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0301 basic medicine ,Cardiac output ,medicine.medical_specialty ,beetroot juice ,Physiology ,030204 cardiovascular system & hematology ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Oxygen Consumption ,0302 clinical medicine ,Nitrate ,nitric oxide ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,skeletal muscle ,nitrite ,Heart Failure ,Exercise Tolerance ,Nitrates ,Ejection fraction ,business.industry ,Skeletal muscle ,VO2 max ,Stroke Volume ,Mini-Review ,medicine.disease ,Bioavailability ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Heart failure ,Dietary Supplements ,Cardiology ,fatigue ,business - Abstract
Heart failure (HF) results in a myriad of central and peripheral abnormalities that impair the ability to sustain skeletal muscle contractions and, therefore, limit tolerance to exercise. Chief among these abnormalities is the lowered maximal oxygen uptake, which is brought about by reduced cardiac output and exacerbated by O2delivery-utilization mismatch within the active skeletal muscle. Impaired nitric oxide (NO) bioavailability is considered to play a vital role in the vascular dysfunction of both reduced and preserved ejection fraction HF (HFrEF and HFpEF, respectively), leading to the pursuit of therapies aimed at restoring NO levels in these patient populations. Considering the complementary role of the nitrate-nitrite-NO pathway in the regulation of enzymatic NO signaling, this review explores the potential utility of inorganic nitrate interventions to increase NO bioavailability in the HFrEF and HFpEF patient population. Although many preclinical investigations have suggested that enhanced reduction of nitrite to NO in low Po2and pH environments may make a nitrate-based therapy especially efficacious in patients with HF, inconsistent results have been found thus far in clinical settings. This brief review provides a summary of the effectiveness (or lack thereof) of inorganic nitrate interventions on exercise tolerance in patients with HFrEF and HFpEF. Focus is also given to practical considerations and current gaps in the literature to facilitate the development of effective nitrate-based interventions to improve exercise tolerance in patients with HF.
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- 2021
7. Numerical solution of Q2 evolution equations for fragmentation functions.
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M. Hirai and S. Kumano
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- 2012
- Full Text
- View/download PDF
8. Commentaries on Viewpoint: The interaction between SARS-CoV-2 and ACE2 may have consequences for skeletal muscle viral susceptibility and myopathies
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John D Biglands, Anderson Meireles, Ana Lilia Rayas-Gómez, Moacir Marocolo, Flávio Antônio de Souza Castro, Sanjeeb Sudarshan Bhandari, Ai Lyn Tan, Matiram Pun, Scott K. Ferguson, Matthew Farrow, Ricardo J. Fernandes, J. Arturo Abraldes, Hiago L. R. de Souza, Daniel M. Hirai, José Manuel González-Rayas, Rhaí André Arriel, Fadia Norma Mobayed-Vega, Michael J. Holmes, Nainoa Calvo, Edilamar Menezes de Oliveira, José Manuel González-Yáñez, Michael D. Belbis, and Tiago Fernandes
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2019-20 coronavirus outbreak ,biology ,Coronavirus disease 2019 (COVID-19) ,Physiology ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Skeletal muscle ,medicine.disease ,biology.organism_classification ,Virology ,Pneumonia ,medicine.anatomical_structure ,Physiology (medical) ,Pandemic ,medicine ,business ,Coronavirus Infections ,Betacoronavirus - Published
- 2020
9. Systemic NOS inhibition reduces contracting muscle oxygenation more in intact female than male rats
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Daniel M. Hirai, David C. Poole, Yutaka Kano, Jesse C. Craig, Trenton D. Colburn, Ayaka Tabuchi, and Timothy I. Musch
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Pentobarbital ,Baroreceptor ,Physiology ,Clinical Biochemistry ,Hemodynamics ,Stimulation ,030204 cardiovascular system & hematology ,Biochemistry ,Nitric oxide ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,Oxygen Consumption ,Sex Factors ,0302 clinical medicine ,Heart Rate ,Internal medicine ,Heart rate ,medicine ,Animals ,Arterial Pressure ,Enzyme Inhibitors ,Muscle, Skeletal ,business.industry ,Skeletal muscle ,Oxygenation ,Oxygen ,NG-Nitroarginine Methyl Ester ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Female ,Nitric Oxide Synthase ,business ,Muscle Contraction ,medicine.drug - Abstract
Females respond to baroreceptor stimulation with enhanced modulation of heart rate (HR) to regulate blood pressure and also express greater reliance on nitric oxide (NO) for vascular control compared to males. Sex differences in muscle oxygenation consequent to central hemodynamic challenge induced by systemic NO synthase (NOS) inhibition are unknown. We tested the hypotheses that systemic NOS inhibition would induce lower contracting skeletal muscle oxygenation in females compared to males. The spinotrapezius of Sprague-Dawley rats (females (♀) = 9, males (♂) = 9) was surgically exposed and contracted by electrical stimulation (180s, 1 Hz, ~6 V) under pentobarbital sodium anesthesia. Oxyphor G4 was injected into the muscle and phosphorescence quenching was used to measure the interstitial PO2 (PO2is, determined by O2 delivery-to-utilization matching) under control (Krebs-Henseleit solution) and after intra-arterial infusion of nitro- l -arginine methyl ester ( l -NAME; NOS blockade; 10 mg kg−1). At rest, females showed a greater PO2is increase (ΔPO2is/ΔMAP) and HR (ΔHR/ΔMAP) reduction than males in response to the elevated MAP induced by systemic NOS inhibition (both p l -NAME, during the contracting steady-state, females exhibited lower PO2is than males (♂: 17.1 ± 1.4 vs ♀: 10.8 ± 1.4 mmHg, p l -NAME-induced elevation of MAP via the baroreceptor reflex and provide new insights on how central hemodynamics affect skeletal muscle oxygenation in a sex-specific manner.
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- 2020
10. Impulse Breakdown Strength of Epoxy/Anatase TiO2 Nanocomposite using Centrifugation Agglomerate Removal
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M. Hirai, M. Kurimoto, S. Yoshida, T. Umemoto, and H. Muto
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- 2021
11. Perceptions Regarding Pediatric and Adolescent Gynecology Training among Obstetrics and Gynecology Residents in Hawai'i
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Cori-Ann M, Hirai, Ingrid Y, Chern, Nikki D S, Kumura, and Mark, Hiraoka
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Obstetrics ,Adolescent ,Gynecology ,Pregnancy ,education ,Humans ,Internship and Residency ,Female ,Curriculum ,Articles ,Child ,Hawaii - Abstract
A pediatric and adolescent gynecology curriculum was implemented for obstetrics/gynecology residents at a single institution in Hawai‘i. The primary objective of this study was to evaluate the effectiveness of this pediatric and adolescent gynecology (PAG) formal curriculum in improving knowledge. Twelve residents at the University of Hawai‘i completed the curriculum during their second year of training. Of these, 6 residents completed an examination assessing knowledge both before and immediately after the curriculum. Five of these residents completed the examination 1-2 years after completing the curriculum. Average pre-rotation examination scores were 57%, which increased significantly immediately after the curriculum to 87% (P=.003) and remained significantly higher after 1-2 years with average scores of 71% (P=.025). A secondary objective was to assess resident comfort and confidence levels in the subject. All residents who completed the curriculum completed surveys assessing comfort in their pediatric and adolescent gynecology training and both perceived confidence and competence in this area. Despite completing the curriculum, 7 of 12 (58%) did not feel comfortable evaluating pediatric gynecology patients, and 5 of 12 (42%) did not feel prepared nor competent to care for pediatric and adolescent patients. A formal pediatric and adolescent gynecology curriculum increased examination performance, which suggests knowledge retention. However, despite curriculum completion, residents still desired more training in the subject area. Residency programs should consider innovative ways to incorporate inpatient and outpatient educational experiences, periodic testing, and feedback longitudinally throughout residency training to improve long-term retention, confidence, and competence in providing gynecologic care in the pediatric and adolescent gynecology population.
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- 2021
12. Effects Of Acute Selective COX-2 Inhibition On Skeletal Muscle Microvascular Oxygenation And Exercise Tolerance
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Michael D. Belbis, Michael J. Holmes, Joseph Yao, Christopher W. Kinnick, Christopher K. Kargl, Carly Day, Nicole L. Noel, Timothy P. Gavin, Bruno T. Roseguini, and Daniel M. Hirai
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Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine - Published
- 2022
13. Fujitsu VP2000 series.
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Nobuo Uchida, M. Hirai, M. Yoshida, and K. Hotta
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- 1990
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14. Skeletal muscle interstitial P<scp>o</scp>2 kinetics during recovery from contractions
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Timothy I. Musch, David C. Poole, Daniel M. Hirai, Jesse C. Craig, Hiroaki Eshima, Yutaka Kano, and Trenton D. Colburn
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Physiology ,Chemistry ,Capillary action ,Kinetics ,Hemodynamics ,Skeletal muscle ,030204 cardiovascular system & hematology ,Muscle oxygenation ,Microcirculation ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Physiology (medical) ,Diffusing capacity ,medicine ,Biophysics ,Flux (metabolism) ,030217 neurology & neurosurgery - Abstract
The oxygen partial pressure in the interstitial space (Po2 is) drives O2 into the myocyte via diffusion, thus supporting oxidative phosphorylation. Although crucial for metabolic recovery and the capacity to perform repetitive tasks, the time course of skeletal muscle Po2 is during recovery from contractions remains unknown. We tested the hypothesis that Po2 is would recover to resting values and display considerable on-off asymmetry (fast on-, slow off-kinetics), reflective of asymmetric capillary hemodynamics. Microvascular Po2 (Po2 mv) was also evaluated to test the hypothesis that a significant transcapillary gradient (ΔPo2 = Po2 mv − Po2 is) would be sustained during recovery. Po2 mv and Po2 is (expressed in mmHg) were determined via phosphorescence quenching in the exposed rat spinotrapezius muscle during and after submaximal twitch contractions ( n = 12). Po2 is rose exponentially ( P < 0.05) from end-contraction (11.1 ± 5.1), such that the end-recovery value (17.9 ± 7.9) was not different from resting Po2 is (18.5 ± 8.1; P > 0.05). Po2 is off-kinetics were slower than on-kinetics (mean response time: 53.1 ± 38.3 versus 18.5 ± 7.3 s; P < 0.05). A significant transcapillary ΔPo2 observed at end-contraction (16.6 ± 7.4) was maintained throughout recovery (end-recovery: 18.8 ± 9.6; P > 0.05). Consistent with our hypotheses, muscle Po2 is recovered to resting values with slower off-kinetics compared with the on-transient in line with the on-off asymmetry for capillary hemodynamics. Maintenance of a substantial transcapillary ΔPo2 during recovery supports that the microvascular-interstitium interface provides considerable resistance to O2 transport. As dictated by Fick’s law (V̇o2 = Do2 × ΔPo2), modulation of O2 flux (V̇o2) during recovery must be achieved via corresponding changes in effective diffusing capacity (Do2; mainly capillary red blood cell hemodynamics and distribution) in the face of unaltered ΔPo2. NEW & NOTEWORTHY Capillary blood-myocyte O2 flux (V̇o2) is determined by effective diffusing capacity (Do2; mainly erythrocyte hemodynamics and distribution) and microvascular-interstitial Po2 gradients (ΔPo2 = Po2 mv − Po2 is). We show that Po2 is demonstrates on-off asymmetry consistent with Po2 mv and erythrocyte kinetics during metabolic transitions. A substantial transcapillary ΔPo2 was preserved during recovery from contractions, indicative of considerable resistance to O2 diffusion at the microvascular-interstitium interface. This reveals that effective Do2 declines in step with V̇o2 during recovery, as per Fick’s law.
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- 2019
15. Commentaries on Viewpoint: Managing the power grid: How myoglobin can regulate P<scp>o</scp>2 and energy distribution in skeletal muscle
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David C. Poole, Jesse C. Craig, Nelson, Daniel M. Hirai, Joshua M. Bock, Trenton D. Colburn, Nicholas T. Kruse, Gunga Hc, Donnelly C, T I. Musch, Tingyang Zhou, Li Zuo, Ryan Rosenberry, Cristancho E, Piknova B, Riveros-Rivera A, Wayne T. Willis, Fenghua Tian, and Liu H
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chemistry.chemical_compound ,medicine.anatomical_structure ,Energy distribution ,Myoglobin ,chemistry ,Physiology ,Physiology (medical) ,medicine ,Skeletal muscle ,Power grid ,Computational biology - Published
- 2019
16. Regulation of capillary hemodynamics by K ATP channels in resting skeletal muscle
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Ayaka Tabuchi, Trenton D. Colburn, David C. Poole, Timothy I. Musch, Jesse C. Craig, and Daniel M. Hirai
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medicine.medical_specialty ,Mean arterial pressure ,Vascular smooth muscle ,Physiology ,microcirculation ,Hemodynamics ,ATP‐sensitive K+ channel ,red blood cell ,030204 cardiovascular system & hematology ,Microcirculation ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,intravital microscopy ,medicine ,blood flow ,QP1-981 ,Membrane potential ,Chemistry ,Skeletal muscle ,Red blood cell ,medicine.anatomical_structure ,Endocrinology ,030217 neurology & neurosurgery ,Intravital microscopy - Abstract
ATP‐sensitive K+ channels (KATP) have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether KATP channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood‐myocyte O2 exchange) remains unknown. We tested the hypothesis that KATP channel inhibition would reduce the proportion of capillaries supporting continuous red blood cell (RBC) flow and impair RBC hemodynamics and distribution in perfused capillaries within resting skeletal muscle. RBC flux (fRBC), velocity (VRBC), and capillary tube hematocrit (Hctcap) were assessed via intravital microscopy of the rat spinotrapezius muscle (n = 6) under control (CON) and glibenclamide (GLI; KATP channel antagonist; 10 µM) superfusion conditions. There were no differences in mean arterial pressure (CON:120 ± 5, GLI:124 ± 5 mmHg; p > 0.05) or heart rate (CON:322 ± 32, GLI:337 ± 33 beats/min; p > 0.05) between conditions. The %RBC‐flowing capillaries were not altered between conditions (CON:87 ± 2, GLI:85 ± 1%; p > 0.05). In RBC‐perfused capillaries, GLI reduced fRBC (CON:20.1 ± 1.8, GLI:14.6 ± 1.3 cells/s; p 0.05). The absence of GLI effects on the %RBC‐flowing capillaries and Hctcap indicates preserved muscle O2 diffusing capacity (DO2m). In contrast, GLI lowered both fRBC and VRBC thus impairing perfusive microvascular O2 transport (Q̇m) and lengthening RBC capillary transit times, respectively. Given the interdependence between diffusive and perfusive O2 conductances (i.e., %O2 extraction∝DO2m/Q̇m), such GLI alterations are expected to elevate muscle %O2 extraction to sustain a given metabolic rate. These results support that KATP channels regulate capillary hemodynamics and, therefore, microvascular gas exchange in resting skeletal muscle.
- Published
- 2021
17. Exercise training decreases intercostal and transversus abdominis muscle blood flows in heart failure rats during submaximal exercise
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Timothy I. Musch, Clark T. Holdsworth, Joshua R. Smith, K. Sue Hageman, David C. Poole, Daniel M. Hirai, Steven W. Copp, and Scott K. Ferguson
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Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Mean arterial pressure ,Physiology ,Diaphragm ,Submaximal exercise ,Intercostal Muscles ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,Random Allocation ,0302 clinical medicine ,Internal medicine ,Physical Conditioning, Animal ,medicine ,Respiratory muscle ,Animals ,Transversus abdominis ,computer.programming_language ,Abdominal Muscles ,Heart Failure ,sed ,business.industry ,General Neuroscience ,Blood flow ,medicine.disease ,Diaphragm (structural system) ,Rats ,Disease Models, Animal ,030228 respiratory system ,Heart failure ,Blood Circulation ,Cardiology ,business ,computer ,030217 neurology & neurosurgery - Abstract
Diaphragm muscle blood flow (BF) and vascular conductance (VC) are elevated with chronic heart failure (HF) during exercise. Exercise training (ExT) elicits beneficial respiratory muscle and pulmonary system adaptations in HF. We hypothesized that diaphragm BF and VC would be lower in HF rats following ExT than their sedentary counterparts (Sed). Respiratory muscle BFs and mean arterial pressure were measured via radiolabeled microspheres and carotid artery catheter, respectively, during submaximal treadmill exercise (20 m/min, 5 % grade). During exercise, no differences were present between HF + ExT and HF + Sed in diaphragm BFs (201 ± 36 vs. 227 ± 44 mL/min/100 g) or VCs (both, p 0.05). HF + ExT compared to HF + Sed had lower intercostal BF (27 ± 3 vs. 41 ± 5 mL/min/100 g) and VC (0.21 ± 0.02 vs. 0.31 ± 0.04 mL/min/mmHg/100 g) during exercise (both, p 0.05). Further, HF + ExT compared to HF + Sed had lower transversus abdominis BF (20 ± 1 vs. 35 ± 6 mL/min/100 g) and VC (0.14 ± 0.02 vs. 0.27 ± 0.05 mL/min/mmHg/100 g) during exercise (both, p 0.05). These data suggest that exercise training lowers the intercostal and transversus abdominis BF responses in HF rats during submaximal treadmill exercise.
- Published
- 2021
18. Regulation of capillary hemodynamics by K
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Daniel M, Hirai, Ayaka, Tabuchi, Jesse C, Craig, Trenton D, Colburn, Timothy I, Musch, and David C, Poole
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Male ,Microcirculation ,Hemodynamics ,microcirculation ,ATP‐sensitive K+ channel ,Original Articles ,red blood cell ,Rats ,Rats, Sprague-Dawley ,Oxygen Consumption ,Hematocrit ,KATP Channels ,Glyburide ,intravital microscopy ,Potassium Channel Blockers ,Animals ,blood flow ,Original Article ,Muscle, Skeletal - Abstract
ATP‐sensitive K+ channels (KATP) have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether KATP channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood‐myocyte O2 exchange) remains unknown. We tested the hypothesis that KATP channel inhibition would reduce the proportion of capillaries supporting continuous red blood cell (RBC) flow and impair RBC hemodynamics and distribution in perfused capillaries within resting skeletal muscle. RBC flux (f RBC), velocity (V RBC), and capillary tube hematocrit (Hctcap) were assessed via intravital microscopy of the rat spinotrapezius muscle (n = 6) under control (CON) and glibenclamide (GLI; KATP channel antagonist; 10 µM) superfusion conditions. There were no differences in mean arterial pressure (CON:120 ± 5, GLI:124 ± 5 mmHg; p > 0.05) or heart rate (CON:322 ± 32, GLI:337 ± 33 beats/min; p > 0.05) between conditions. The %RBC‐flowing capillaries were not altered between conditions (CON:87 ± 2, GLI:85 ± 1%; p > 0.05). In RBC‐perfused capillaries, GLI reduced f RBC (CON:20.1 ± 1.8, GLI:14.6 ± 1.3 cells/s; p 0.05). The absence of GLI effects on the %RBC‐flowing capillaries and Hctcap indicates preserved muscle O2 diffusing capacity (DO2m). In contrast, GLI lowered both f RBC and V RBC thus impairing perfusive microvascular O2 transport (Q̇m) and lengthening RBC capillary transit times, respectively. Given the interdependence between diffusive and perfusive O2 conductances (i.e., %O2 extraction∝DO2m/Q̇m), such GLI alterations are expected to elevate muscle %O2 extraction to sustain a given metabolic rate. These results support that KATP channels regulate capillary hemodynamics and, therefore, microvascular gas exchange in resting skeletal muscle., Superfusion of the rat spinotrapezius muscle with the sulfonylurea glibenclamide (GLI) was used to locally inhibit KATP channels in vivo. GLI reduced both red blood cell (RBC) flux and velocity thereby impairing perfusive microvascular O2 transport and lengthening RBC capillary transit times, respectively. These results support that KATP channels regulate capillary hemodynamics and microvascular gas exchange in resting skeletal muscle.
- Published
- 2021
19. Acute effects of leg heat therapy on walking performance and cardiovascular and inflammatory responses to exercise in patients with peripheral artery disease
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Daniel M. Hirai, Bruno T. Roseguini, Raghu L. Motaganahalli, Qifan Song, Jacob C. Monroe, and Michael S. Emery
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Male ,heat therapy ,medicine.medical_specialty ,endothelin‐1 ,Physiology ,medicine.medical_treatment ,Diastole ,Walking ,030204 cardiovascular system & hematology ,peripheral artery disease ,Peripheral Arterial Disease ,03 medical and health sciences ,Oxygen Consumption ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,medicine ,QP1-981 ,Humans ,Treadmill ,Aged ,Original Research ,Endothelin-1 ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,business.industry ,blood pressure ,Hyperthermia, Induced ,intermittent claudication ,Oxygenation ,Middle Aged ,Crossover study ,Heat therapy ,Intermittent claudication ,Blood pressure ,Cardiology ,Female ,medicine.symptom ,Claudication ,business ,030217 neurology & neurosurgery - Abstract
Lower‐extremity peripheral artery disease (PAD) is associated with increased risk of cardiovascular events and impaired exercise tolerance. We have previously reported that leg heat therapy (HT) applied using liquid‐circulating trousers perfused with warm water increases leg blood flow and reduces blood pressure (BP) and the circulating levels of endothelin‐1 (ET‐1) in patients with symptomatic PAD. In this sham‐controlled, randomized, crossover study, sixteen patients with symptomatic PAD (age 65 ± 5.7 years and ankle‐brachial index: 0.69 ± 0.1) underwent a single 90‐min session of HT or a sham treatment prior to a symptom‐limited, graded cardiopulmonary exercise test on the treadmill. The primary outcome was the peak walking time (PWT) during the exercise test. Secondary outcomes included the claudication onset time (COT), resting and exercise BP, calf muscle oxygenation, pulmonary oxygen uptake (V̇O2), and plasma levels of ET‐1, interleukin‐6 (IL‐6) and tumor necrosis factor‐alpha (TNF‐α). Systolic, but not diastolic BP, was significantly lower (~7 mmHg, p, We show that a single session of leg heat therapy (HT) reduces systolic blood pressure and lowers post‐exercise circulating levels of the potent vasoconstrictor endothelin‐1. Leg HT also tended to improve peak walking time during a graded treadmill test. This practical and well‐tolerated therapy may be a useful adjunctive tool to improve cardiovascular health and restore functional capacity in PAD patients.
- Published
- 2020
20. The effect of dietary nitrate supplementation on the speed-duration relationship in mice with sickle cell disease
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Katherine Redinius, Andrew M. Jones, David Irwin, David I. Pak, Kurt R. Stenmark, Julie W. Harral, Delaney C. Swindle, Jamie R. Blackwell, Paul W. Buehler, Daniel M. Hirai, and Scott K. Ferguson
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medicine.medical_specialty ,Physiology ,Cell ,Exercise intolerance ,Disease ,Anemia, Sickle Cell ,030204 cardiovascular system & hematology ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Oxygen Consumption ,Double-Blind Method ,Physiology (medical) ,Internal medicine ,Dietary Nitrate ,medicine ,Animals ,Humans ,Exercise Tolerance ,Nitrates ,business.industry ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Dietary Supplements ,Skeletal muscle blood flow ,Free hemoglobin ,medicine.symptom ,Beta vulgaris ,business ,030217 neurology & neurosurgery ,Research Article - Abstract
Sickle cell disease (SCD) causes exercise intolerance likely due to impaired skeletal muscle function and low nitric oxide (NO) bioavailability. Dietary nitrate improves hemodynamic and metabolic control during exercise in humans and animals. The purpose of this investigation was to assess the impact of nitrate supplementation on exercise capacity as measured by the running speed to exercise duration relationship [critical speed (CS)]in mice with SCD. We tested the hypothesis that nitrate supplementation via beetroot juice (BR) would attenuate the exercise intolerance observed in mice with SCD. Ten wild-type (WT) and 18 Berkley sickle-cell mice (BERK) received water (WT: n = 10, BERK: n = 10) or nitrate-rich BR (BERK+BR: n = 8, nitrate dose 1 mmol/kg/day) for 5 days. Following the supplementation period, all mice performed 3–5 constant-speed treadmill tests that resulted in exhaustion within 1.5 to 20 min. Time to exhaustion vs. treadmill speed was fit to a hyperbolic model to determine CS. CS was significantly lower in BERK vs. WT and BERK+BR with no significant difference between WT and BERK+BR (WT: 36.6 ± 1.6, BERK: 23.8 ± 1.5, BERK+BR: 31.1 ± 2.1 m/min, P < 0.05). Exercise tolerance, measured via CS, was significantly lower in BERK mice relative to WT. However, BERK mice receiving 5 days of nitrate supplementation exhibited no difference in exercise tolerance when compared with WT. These results support the potential utility of a dietary nitrate intervention to improve functionality in SCD patients. NEW & NOTEWORTHY Sickle cell disease compromises muscle O(2) delivery resulting in exercise intolerance. Dietary nitrate supplementation increases skeletal muscle blood flow during exercise and may improve exercise capacity in a mouse model of sickle cell disease. We investigated the effects of dietary nitrate supplementation on exercise tolerance in a mouse model of sickle cell disease using the treadmill speed-duration relationship (critical speed). Mice with sickle cell disease provided with a dietary nitrate supplement had a critical speed not significantly different from healthy wild-type mice.
- Published
- 2020
21. Transcapillary PO(2) Gradients in Contracting Muscles Across the Fibre Type and Oxidative Continuum
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Daniel M. Hirai, David C. Poole, Ramona E. Weber, Trenton D. Colburn, Brad J. Behnke, Scott K. Ferguson, Jesse C. Craig, Timothy I. Musch, and Kiana M. Schulze
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inorganic chemicals ,0301 basic medicine ,Physiology ,Hemodynamics ,Oxidative phosphorylation ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Oxygen Consumption ,Interstitial space ,medicine ,Animals ,Glycolysis ,Muscle, Skeletal ,Pressure gradient ,Chemistry ,Microcirculation ,Oxygen transport ,Skeletal muscle ,respiratory system ,Rats ,Oxygen ,Red blood cell ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,cardiovascular system ,Biophysics ,030217 neurology & neurosurgery ,circulatory and respiratory physiology ,Muscle Contraction - Abstract
KEY POINTS Within skeletal muscle the greatest resistance to oxygen transport is thought to reside across the short distance at the red blood cell-myocyte interface. These structures generate a significant transmural oxygen pressure (PO2 ) gradient in mixed fibre-type muscle. Increasing O2 flux across the capillary wall during exercise depends on: (i) the transmural O2 pressure gradient, which is maintained in mixed-fibre muscle, and/or (ii) elevating diffusing properties between microvascular and interstitial compartments resulting, in part, from microvascular haemodynamics and red blood cell distribution. We evaluated the PO2 within the microvascular and interstitial spaces of muscles spanning the slow- to fast-twitch fibre and high- to low-oxidative capacity spectrums, at rest and during contractions, to assess the magnitude of transcapillary PO2 gradients in rats. Our findings demonstrate that, across the metabolic rest-contraction transition, the transcapillary pressure gradient for O2 flux is: (i) maintained in all muscle types, and (ii) the lowest in contracting highly oxidative fast-twitch muscle. ABSTRACT In mixed fibre-type skeletal muscle transcapillary PO2 gradients (PO2 mv-PO2 is; microvascular and interstitial, respectively) drive O2 flux across the blood-myocyte interface where the greatest resistance to that O2 flux resides. We assessed a broad spectrum of fibre-type and oxidative-capacity rat muscles across the rest-to-contraction (1 Hz, 120 s) transient to test the novel hypotheses that: (i) slow-twitch PO2 is would be greater than fast-twitch, (ii) muscles with greater oxidative capacity have greater PO2 is than glycolytic counterparts, and (iii) whether PO2 mv-PO2 is at rest is maintained during contractions across all muscle types. PO2 mv and PO2 is were determined via phosphorescence quenching in soleus (SOL; 91% type I+IIa fibres and CSa: ∼21 μmol min-1 g-1 ), peroneal (PER; 33% and ∼20 μmol min-1 g-1 ), mixed (MG; 9% and ∼26 μmol min-1 g-1 ) and white gastrocnemius (WG; 0% and ∼8 μmol min-1 g-1 ) across the rest-contraction transient. PO2 mv was higher than PO2 is in each muscle (∼6-13 mmHg; P
- Published
- 2020
22. Long-Term Survival after Adrenalectomy for Asynchronous Metastasis of Bladder Cancer to the Bilateral Adrenal Glands
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S. Washino, M. Hirai, A. Matsuzaki, and Y. Kobayashi
- Subjects
Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Isolated adrenal metastasis of bladder cancer, particularly the bilateral, is quite rare. Systemic chemotherapy is the treatment of choice for metastatic urothelial carcinoma. However, despite initially promising response rates of approximately 45%–71%, most tumors eventually show progression, and the median survival time following chemotherapy regimen is approximately 14-15 months. Recently, favorable results of surgery for metastatic urothelial carcinoma have been reported. Here, we report a rare case of asynchronous metastasis of bladder cancer to the bilateral adrenal glands with long-term survival after bilateral adrenalectomy. A 69-year-old man underwent radical cystoprostatectomy and ileal conduit urinary diversion for invasive bladder cancer. Ten months later, left adrenalectomy was performed for a left adrenal tumor, revealing metastatic urothelial carcinoma. After adjuvant chemotherapy, a tumor in the right adrenal gland was detected. Right adrenalectomy was done, and the tumor was also found to be metastatic urothelial carcinoma. The patient had an uneventful recovery after starting steroid replacement therapy. Three years later, he was doing well and had no evidence of recurrence. Adrenalectomy for isolated adrenal metastasis of urothelial carcinoma may be a reasonable option, even if such metastases are bilateral.
- Published
- 2012
- Full Text
- View/download PDF
23. Sex and nitric oxide bioavailability interact to modulate interstitial P<scp>o</scp>2in healthy rat skeletal muscle
- Author
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Daniel M. Hirai, David C. Poole, Jesse C. Craig, Timothy I. Musch, Trenton D. Colburn, and Michael J. Schettler
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Physiology ,Skeletal muscle ,030204 cardiovascular system & hematology ,Bioavailability ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine.anatomical_structure ,chemistry ,Physiology (medical) ,Oxygen delivery ,Biophysics ,medicine ,Flux (metabolism) ,030217 neurology & neurosurgery - Abstract
Premenopausal women express reduced blood pressure and risk of cardiovascular disease relative to age-matched men. This purportedly relates to elevated estrogen levels increasing nitric oxide synthase (NOS) activity and NO-mediated vasorelaxation. We tested the hypotheses that female rat skeletal muscle would: 1) evince a higher O2delivery-to-utilization ratio (Q̇o2/V̇o2) during contractions; and 2) express greater modulation of Q̇o2/V̇o2with changes to NO bioavailability compared with male rats. The spinotrapezius muscle of Sprague-Dawley rats (females = 8, males = 8) was surgically exposed and electrically-stimulated (180 s, 1 Hz, 6 V). OxyphorG4 was injected into the muscle and phosphorescence quenching employed to determine the temporal profile of interstitial Po2(Po2is, determined by Q̇o2/V̇o2). This was performed under three conditions: control (CON), 300 µM sodium nitroprusside (SNP; NO donor), and 1.5 mM Nω-nitro-l-arginine methyl ester (l-NAME; NOS blockade) superfusion. No sex differences were found for the Po2iskinetics parameters in CON or l-NAME ( P > 0.05), but females elicited a lower baseline following SNP (males 42 ± 3 vs. females 36 ± 2 mmHg, P < 0.05). Females had a lower ΔPo2isduring contractions following SNP (males 22 ± 3 vs. females 17 ± 2 mmHg, P < 0.05), but there were no sex differences for the temporal response to contractions ( P > 0.05). The total NO effect (SNP minus l-NAME) on Po2iswas not different between sexes. However, the spread across both conditions was shifted to a lower absolute range for females (reduced SNP baseline and greater reduction following l-NAME). These data support that females have a greater reliance on basal NO bioavailability and males have a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.NEW & NOTEWORTHY Interstitial Po2(Po2is; determined by O2delivery-to-utilization matching) plays an important role for O2flux into skeletal muscle. We show that both sexes regulate Po2isat similar levels at rest and during skeletal muscle contractions. However, modulating NO bioavailability exposes sex differences in this regulation with females potentially having a greater reliance on basal NO bioavailability and males having a greater responsiveness to exogenous NO and less responsiveness to reduced endogenous NO.
- Published
- 2018
24. Neuronal nitric oxide synthase regulation of skeletal muscle functional hyperemia: exercise training and moderate compensated heart failure
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Steven W. Copp, Scott K. Ferguson, David C. Poole, Timothy I. Musch, K. Sue Hageman, Clark T. Holdsworth, and Daniel M. Hirai
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Physiology ,Clinical Biochemistry ,Hyperemia ,Vasodilation ,Nitric Oxide Synthase Type I ,Hindlimb ,030204 cardiovascular system & hematology ,Biochemistry ,Article ,Nitric oxide ,Rats, Sprague-Dawley ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Physical Conditioning, Animal ,Internal medicine ,Animals ,Medicine ,Myocardial infarction ,Muscle, Skeletal ,Heart Failure ,business.industry ,Skeletal muscle ,Blood flow ,medicine.disease ,Rats ,Preload ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Heart failure ,business ,030217 neurology & neurosurgery - Abstract
Nitric oxide (NO) modulates oxygen delivery-utilization matching in resting and contracting skeletal muscle. Recent reports indicate that neuronal NO synthase (nNOS)-mediated vasoregulation during contractions is enhanced with exercise training and impaired with chronic heart failure (HF). Consequently, we tested the hypothesis that selective nNOS inhibition (S-methyl-l-thiocitrulline; SMTC, 2.1 µmol/kg) would produce attenuated reductions in muscle blood flow during moderate/heavy submaximal exercise in sedentary HF rats compared to their healthy counterparts. In addition, SMTC was expected to evoke greater reductions in exercising muscle blood flow in trained compared to sedentary healthy and HF rats. Blood flow during submaximal treadmill running (20 min/m, 5% grade) was determined via radiolabeled microspheres pre- and post-SMTC administration in healthy sedentary (Healthy + Sed, n = 8), healthy exercise trained (Healthy + ExT, n = 8), HF sedentary (HF + Sed, left ventricular end-diastolic pressure (LVEDP) = 12 ± 1 mmHg, n = 8), and HF exercise trained (HF + ExT, LVEDP = 16 ± 2 mmHg, n = 7) rats. nNOS contribution to exercising total hindlimb blood flow (ml/min/100 g) was not increased by training in either healthy or HF groups (Healthy + Sed: 105 ± 11 vs. 108 ± 16; Healthy + ExT: 96 ± 9 vs. 91 ± 7; HF + Sed: 124 ± 6 vs. 110 ± 12; HF + ExT: 107 ± 13 vs. 101 ± 8; control vs. SMTC, respectively; p > .05 for all). Similarly, SMTC did not reduce exercising blood flow in the majority of individual hindlimb muscles in any group (p > .05 for all, except for the semitendinosus and adductor longus in HF + Sed and the adductor longus in HF + ExT; p < .05). Contrary to our hypothesis, we find no support for either upregulation of nNOS function contributing to exercise hyperemia after training or its dysregulation with chronic HF.
- Published
- 2018
25. Skeletal muscle microvascular and interstitial PO2 from rest to contractions
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David C. Poole, Daniel M. Hirai, Hiroaki Eshima, William L. Sexton, Yutaka Kano, Jesse C. Craig, Timothy I. Musch, and Trenton D. Colburn
- Subjects
Sarcolemma ,Physiology ,Chemistry ,Oxygen transport ,Skeletal muscle ,chemistry.chemical_element ,Hemodynamics ,030204 cardiovascular system & hematology ,Oxygen ,03 medical and health sciences ,0302 clinical medicine ,medicine.anatomical_structure ,Interstitial space ,Diffusing capacity ,medicine ,Biophysics ,Myocyte ,030217 neurology & neurosurgery - Abstract
KEY POINTS Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these transmural gradients is proportional to the local resistance. The greatest resistance to oxygen transport into skeletal muscle is considered to reside in the short distance between red blood cells and myocytes. Although crucial to oxygen transport, little is known about transmural pressure gradients within skeletal muscle during contractions. We evaluated oxygen pressures within both the skeletal muscle microvascular and interstitial spaces to determine transmural gradients during the rest-contraction transient in anaesthetized rats. The significant transmural gradient observed at rest was sustained during submaximal muscle contractions. Our findings support that the blood-myocyte interface provides substantial resistance to oxygen diffusion at rest and during contractions and suggest that modulations in microvascular haemodynamics and red blood cell distribution constitute primary mechanisms driving increased transmural oxygen flux with contractions. ABSTRACT Oxygen pressure (PO2) gradients across the blood-myocyte interface are required for diffusive O2 transport, thereby supporting oxidative metabolism. The greatest resistance to O2 flux into skeletal muscle is considered to reside between the erythrocyte surface and adjacent sarcolemma, although this has not been measured during contractions. We tested the hypothesis that O2 gradients between skeletal muscle microvascular (PO2 mv ) and interstitial (PO2 is ) spaces would be present at rest and maintained or increased during contractions. PO2 mv and PO2 is were determined via phosphorescence quenching (Oxyphor probes G2 and G4, respectively) in the exposed rat spinotrapezius during the rest-contraction transient (1 Hz, 6 V; n = 8). PO2 mv was higher than PO2 is in all instances from rest (34.9 ± 6.0 versus 15.7 ± 6.4) to contractions (28.4 ± 5.3 versus 10.6 ± 5.2 mmHg, respectively) such that the mean PO2 gradient throughout the transient was 16.9 ± 6.6 mmHg (P 0.05). However, the speed of the PO2 is fall during contractions was slower than that of PO2 mv (time constant: 12.8 ± 4.7 versus 9.0 ± 5.1 s, respectively; P
- Published
- 2018
26. Rare cause of lower gastrointestinal bleeding: Iliac aneurysmo‐colonic fistula after endovascular treatment
- Author
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M Hirai, A Tabayashi, Yosuke Toya, Takayuki Matsumoto, S Yanai, and A Kikuchi
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medicine.medical_specialty ,Lower gastrointestinal bleeding ,Hepatology ,Colonic Fistula ,business.industry ,Endovascular Procedures ,Gastroenterology ,medicine.disease ,Surgery ,Intestinal Fistula ,medicine ,Humans ,Endovascular treatment ,Gastrointestinal Hemorrhage ,business - Published
- 2021
27. Vascular KATP channels mitigate severe muscle O2 delivery-utilization mismatch during contractions in chronic heart failure rats
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Jesse C. Craig, Trenton D. Colburn, Daniel M. Hirai, David C. Poole, Clark T. Holdsworth, Alexander J. Fees, Timothy I. Musch, and Scott K. Ferguson
- Subjects
Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Physiology ,Myocardial Infarction ,Blood Pressure ,030204 cardiovascular system & hematology ,Article ,Rats, Sprague-Dawley ,Glibenclamide ,03 medical and health sciences ,chemistry.chemical_compound ,Oxygen Consumption ,0302 clinical medicine ,KATP Channels ,Heart Rate ,Internal medicine ,Administration, Inhalation ,Heart rate ,medicine ,Animals ,Heart Failure ,Analysis of Variance ,business.industry ,General Neuroscience ,Skeletal muscle ,Oxygenation ,medicine.disease ,Rats ,Oxygen ,Disease Models, Animal ,Blood pressure ,medicine.anatomical_structure ,chemistry ,Anesthesia ,Heart failure ,Chronic Disease ,Pinacidil ,Cardiology ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Muscle Contraction ,Muscle contraction ,medicine.drug - Abstract
The vascular ATP-sensitive K+ (KATP) channel is a mediator of skeletal muscle microvascular oxygenation (PO2mv) during contractions in health. We tested the hypothesis that KATP channel function is preserved in chronic heart failure (CHF) and therefore its inhibition would reduce PO2mv and exacerbate the time taken to reach the PO2mv steady-state during contractions of the spinotrapezius muscle. Moreover, we hypothesized that subsequent KATP channel activation would oppose the effects of this inhibition. Muscle PO2mv (phosphorescence quenching) was measured during 180 s of 1-Hz twitch contractions (~6 V) under control, glibenclamide (GLI, KATP channel antagonist; 5 mg/kg) and pinacidil (PIN, KATP channel agonist; 5 mg/kg) conditions in 16 male Sprague-Dawley rats with CHF induced via myocardial infarction (coronary artery ligation, left ventricular end-diastolic pressure: 18±1 mmHg). GLI reduced baseline PO2mv (control: 28.3±0.9, GLI: 24.8±1.0 mmHg, p
- Published
- 2017
28. Does Exercise Ventilatory Inefficiency Predict Poor Outcome in Heart Failure Patients With COPD?
- Author
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Aline Souza, Flavio F. Arbex, Alcides Rocha, Maria Clara N. Alencar, J. Alberto Neder, Dirceu R. Almeida, Adriana Mazzuco, Frederico José Neves Mancuso, Denis E. OʼDonnel, Daniel M. Hirai, Priscila A. Sperandio, Danilo C. Berton, and Audrey Borghi-Silva
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Cardiovascular event ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Cardiopulmonary exercise test ,medicine ,Humans ,Prospective Studies ,Lung ,Aged ,Heart Failure ,COPD ,Exercise Tolerance ,Ejection fraction ,business.industry ,Rehabilitation ,medicine.disease ,Respiratory Function Tests ,Patient Outcome Assessment ,030228 respiratory system ,Fractional area change ,Heart failure ,Cardiology ,Pulmonary Ventilation ,Cardiology and Cardiovascular Medicine ,Inefficiency ,business ,Respiratory minute volume ,Follow-Up Studies - Abstract
To investigate whether the opposite effects of heart failure (HF) and chronic obstructive pulmonary disease (COPD) on exercise ventilatory inefficiency (minute ventilation [(Equation is included in full-text article.)E]-carbon dioxide output [(Equation is included in full-text article.)CO2] relationship) would negatively impact its prognostic relevance.After treatment optimization and an incremental cardiopulmonary exercise test, 30 male patients with HF-COPD (forced expiratory volume in 1 second [FEV1] = 57% ± 17% predicted, ejection fraction = 35% ± 6%) were prospectively followed up during 412 ± 261 days for major cardiac events.Fourteen patients (46%) had a negative outcome. Patients who had an event had lower echocardiographically determined right ventricular fractional area change (RVFAC), greater ventilatory inefficiency (higher (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir), and lower end-tidal CO2 (PETCO2) (all P.05). Multivariate Cox models revealed that (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir36, ΔPETCO2(PEAK-REST)≥2 mm Hg, and PETCO2PEAK≤33 mm Hg added prognostic value to RVFAC≤45%. Kaplan-Meyer analyses showed that although 18% of patients with RVFAC45% had a major cardiac event after 1 year, no patient with RVFAC45% and (Equation is included in full-text article.)E/(Equation is included in full-text article.)CO2 nadir ≤36 (or PETCO2PEAK33 mm Hg) had a negative event. Conversely, although 69% of patients with RVFAC≤45% had a major cardiac event after 1 year, all patients with RVFAC≤45% and ΔPETCO2(PEAK-REST)≥2 mm Hg had a negative event.Ventilatory inefficiency remains a powerful prognostic marker in HF despite the presence of mechanical ventilatory constraints induced by COPD. If these preliminary findings are confirmed in larger studies, optimal thresholds for outcome prediction are likely greater than those traditionally recommended for HF patients without COPD.
- Published
- 2016
29. Skeletal muscle interstitial Po
- Author
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Daniel M, Hirai, Jesse C, Craig, Trenton D, Colburn, Hiroaki, Eshima, Yutaka, Kano, Timothy I, Musch, and David C, Poole
- Subjects
Male ,Muscle Cells ,Microcirculation ,Hemodynamics ,Capillaries ,Rats ,Oxygen ,Rats, Sprague-Dawley ,Kinetics ,Oxygen Consumption ,Animals ,Muscle, Skeletal ,Muscle Contraction ,Research Article - Abstract
The oxygen partial pressure in the interstitial space (Po(2 is)) drives O(2) into the myocyte via diffusion, thus supporting oxidative phosphorylation. Although crucial for metabolic recovery and the capacity to perform repetitive tasks, the time course of skeletal muscle Po(2 is) during recovery from contractions remains unknown. We tested the hypothesis that Po(2 is) would recover to resting values and display considerable on-off asymmetry (fast on-, slow off-kinetics), reflective of asymmetric capillary hemodynamics. Microvascular Po(2) (Po(2 mv)) was also evaluated to test the hypothesis that a significant transcapillary gradient (ΔPo(2) = Po(2 mv) − Po(2 is)) would be sustained during recovery. Po(2 mv) and Po(2 is) (expressed in mmHg) were determined via phosphorescence quenching in the exposed rat spinotrapezius muscle during and after submaximal twitch contractions (n = 12). Po(2 is) rose exponentially (P < 0.05) from end-contraction (11.1 ± 5.1), such that the end-recovery value (17.9 ± 7.9) was not different from resting Po(2 is) (18.5 ± 8.1; P > 0.05). Po(2 is) off-kinetics were slower than on-kinetics (mean response time: 53.1 ± 38.3 versus 18.5 ± 7.3 s; P < 0.05). A significant transcapillary ΔPo(2) observed at end-contraction (16.6 ± 7.4) was maintained throughout recovery (end-recovery: 18.8 ± 9.6; P > 0.05). Consistent with our hypotheses, muscle Po(2 is) recovered to resting values with slower off-kinetics compared with the on-transient in line with the on-off asymmetry for capillary hemodynamics. Maintenance of a substantial transcapillary ΔPo(2) during recovery supports that the microvascular-interstitium interface provides considerable resistance to O(2) transport. As dictated by Fick’s law (V̇o(2) = Do(2) × ΔPo(2)), modulation of O(2) flux (V̇o(2)) during recovery must be achieved via corresponding changes in effective diffusing capacity (Do(2); mainly capillary red blood cell hemodynamics and distribution) in the face of unaltered ΔPo(2). NEW & NOTEWORTHY Capillary blood-myocyte O(2) flux (V̇o(2)) is determined by effective diffusing capacity (Do(2); mainly erythrocyte hemodynamics and distribution) and microvascular-interstitial Po(2) gradients (ΔPo(2) = Po(2 mv) − Po(2 is)). We show that Po(2 is) demonstrates on-off asymmetry consistent with Po(2 mv) and erythrocyte kinetics during metabolic transitions. A substantial transcapillary ΔPo(2) was preserved during recovery from contractions, indicative of considerable resistance to O(2) diffusion at the microvascular-interstitium interface. This reveals that effective Do(2) declines in step with V̇o(2) during recovery, as per Fick’s law.
- Published
- 2019
30. Central and peripheral factors mechanistically linked to exercise intolerance in heart failure with reduced ejection fraction
- Author
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Ayaka Tabuchi, David C. Poole, Trenton D. Colburn, Jacob T. Caldwell, Jesse C. Craig, Daniel M. Hirai, Bradley J. Behnke, Carl J. Ade, Timothy I. Musch, and Dryden R. Baumfalk
- Subjects
medicine.medical_specialty ,Cardiac Catheterization ,Time Factors ,Physiology ,Myocardial Infarction ,Exercise intolerance ,Nitric Oxide ,Ventricular Function, Left ,Running ,Rats, Sprague-Dawley ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,medicine ,Ventricular Pressure ,Animals ,Muscle, Skeletal ,Heart Failure ,Ejection fraction ,Exercise Tolerance ,business.industry ,Stroke Volume ,medicine.disease ,Echocardiography, Doppler ,Peripheral ,Disease Models, Animal ,Muscle Fibers, Slow-Twitch ,Heart failure ,Muscle Fibers, Fast-Twitch ,Cardiology ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Oxidation-Reduction ,Research Article ,Muscle Contraction - Abstract
Exercise intolerance is a primary symptom of heart failure (HF); however, the specific contribution of central and peripheral factors to this intolerance is not well described. The hyperbolic relationship between exercise intensity and time to exhaustion (speed-duration relationship) defines exercise tolerance but is underused in HF. We tested the hypotheses that critical speed (CS) would be reduced in HF, resting central functional measurements would correlate with CS, and the greatest HF-induced peripheral dysfunction would occur in more oxidative muscle. Multiple treadmill-constant speed runs to exhaustion were used to quantify CS and D′ (distance coverable above CS) in healthy control (Con) and HF rats. Central function was determined via left ventricular (LV) Doppler echocardiography [fractional shortening (FS)] and a micromanometer-tipped catheter [LV end-diastolic pressure (LVEDP)]. Peripheral O2 delivery-to-utilization matching was determined via phosphorescence quenching (interstitial Po2, Po2 is) in the soleus and white gastrocnemius during electrically induced twitch contractions (1 Hz, 8V). CS was lower in HF compared with Con (37 ± 1 vs. 44 ± 1 m/min, P < 0.001), but D′ was not different (77 ± 8 vs. 69 ± 13 m, P = 0.6). HF reduced FS (23 ± 2 vs. 47 ± 2%, P < 0.001) and increased LVEDP (15 ± 1 vs. 7 ± 1 mmHg, P < 0.001). CS was related to FS ( r = 0.72, P = 0.045) and LVEDP ( r = −0.75, P = 0.02) only in HF. HF reduced soleus Po2 is at rest and during contractions (both P < 0.01) but had no effect on white gastrocnemius Po2 is ( P > 0.05). We show in HF rats that decrements in central cardiac function relate directly with impaired exercise tolerance (i.e., CS) and that this compromised exercise tolerance is likely due to reduced perfusive and diffusive O2 delivery to oxidative muscles. NEW & NOTEWORTHY We show that critical speed (CS), which defines the upper boundary of sustainable activity, can be resolved in heart failure (HF) animals and is diminished compared with controls. Central cardiac function is strongly related with CS in the HF animals, but not controls. Skeletal muscle O2 delivery-to-utilization dysfunction is evident in the more oxidative, but not glycolytic, muscles of HF rats and is explained, in part, by reduced nitric oxide bioavailability.
- Published
- 2019
31. Commentaries on Viewpoint: Managing the power grid: How myoglobin can regulate Po
- Author
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Joshua M, Bock, Nicholas T, Kruse, Chris, Donnelly, Daniel M, Hirai, Jesse C, Craig, Trenton D, Colburn, Timothy I, Musch, David C, Poole, Ryan, Rosenberry, Fenghua, Tian, Hanli, Liu, Michael D, Nelson, Barbora, Piknova, Wayne T, Willis, Li, Zuo, Tingyang, Zhou, Alain, Riveros-Rivera, Edgar, Cristancho, and Hanns-Christian, Gunga
- Subjects
Oxygen Consumption ,Viewpoint ,Myoglobin ,Muscle, Skeletal - Published
- 2019
32. Sexual dimorphism in the control of skeletal muscle interstitial Po(2) of heart failure rats: effects of dietary nitrate supplementation
- Author
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Daniel M. Hirai, David C. Poole, Jesse C. Craig, Timothy I. Musch, and Trenton D. Colburn
- Subjects
Male ,medicine.medical_specialty ,Physiology ,030204 cardiovascular system & hematology ,Nitric Oxide ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,Dietary Nitrate ,medicine ,Animals ,Muscle, Skeletal ,Heart Failure ,Sex Characteristics ,Nitrates ,business.industry ,Skeletal muscle ,medicine.disease ,Rats ,Sexual dimorphism ,Oxygen ,Endocrinology ,medicine.anatomical_structure ,Heart failure ,Dietary Supplements ,Oxygen delivery ,Female ,Nitrogen Oxides ,business ,030217 neurology & neurosurgery ,Research Article ,Muscle Contraction - Abstract
Sex differences in the mechanisms underlying cardiovascular pathophysiology of O2 transport in heart failure (HF) remain to be explored. In HF, nitric oxide (NO) bioavailability is reduced and contributes to deficits in O2 delivery-to-utilization matching. Females may rely more on NO for cardiovascular control and as such experience greater decrements in HF. We tested the hypotheses that moderate HF induced by myocardial infarction would attenuate the skeletal muscle interstitial Po2 response to contractions (Po2is; determined by O2 delivery-to-utilization matching) compared with healthy controls and females would express greater dysfunction than male counterparts. Furthermore, we hypothesized that 5 days of dietary nitrate supplementation (Nitrate; 1 mmol·kg−1·day−1) would raise Po2is in HF rats. Forty-two Sprague-Dawley rats were randomly assigned to healthy, HF, or HF + Nitrate groups (each n = 14; 7 female/7 male). Spinotrapezius Po2is was measured via phosphorescence quenching during electrically induced twitch contractions (180 s; 1 Hz). HF reduced resting Po2is for both sexes compared with healthy controls ( P < 0.01), and females were lower than males (14 ± 1 vs. 17 ± 2 mmHg) ( P < 0.05). In HF both sexes expressed reduced Po2is amplitudes following the onset of muscle contractions compared with healthy controls (female: −41 ± 7%, male: −26 ± 12%) ( P < 0.01). In HF rats, Nitrate elevated resting Po2is to values not different from healthy rats and removed the sex difference. Female HF + Nitrate rats expressed greater resting Po2is and amplitudes compared with female HF ( P < 0.05). In this model of moderate HF, O2 delivery-to-utilization matching in the interstitial space is diminished in a sex-specific manner and dietary nitrate supplementation may serve to offset this reduction in HF rats with greater effects in females. NEW & NOTEWORTHY Interstitial Po2 (Po2is; indicative of O2 delivery-to-utilization matching) determines, in part, O2 flux into skeletal muscle. We show that heart failure (HF) reduces Po2is at rest and during skeletal muscle contractions in rats and this negative effect is amplified for females. However, elevating NO bioavailability with dietary nitrate supplementation increases resting Po2is and alters the dynamic response with greater efficacy in female HF rats, particularly at rest and following the onset of muscle contractions.
- Published
- 2019
33. Submaximal exercise cardiac output is increased by 4 weeks of sprint interval training in young healthy males with low initial Q̇-V̇O2: Importance of cardiac response phenotype
- Author
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Brendon J. Gurd, Joe Quadrilatero, Michael E. Tschakovsky, James P. Raleigh, Matthew D. Giles, Daniel M. Hirai, J. Alberto Neder, Joshua H. Jones, Joel T. Zelt, and Robert F. Bentley
- Subjects
Male ,Cardiac response ,Cardiac output ,Physiology ,Blood Pressure ,Submaximal exercise ,High-Intensity Interval Training ,030204 cardiovascular system & hematology ,Vascular Medicine ,Interval training ,0302 clinical medicine ,Blood Flow ,Medicine and Health Sciences ,Public and Occupational Health ,Cardiac Output ,Musculoskeletal System ,Mathematics ,Exercise Tolerance ,Multidisciplinary ,Muscles ,Respiration ,Adaptation, Physiological ,Sports Science ,Body Fluids ,Chemistry ,Phenotype ,Blood ,Sprint ,Physical Sciences ,Cardiology ,Medicine ,Anatomy ,High-intensity interval training ,Research Article ,Chemical Elements ,Adult ,medicine.medical_specialty ,Science ,03 medical and health sciences ,Oxygen Consumption ,Text mining ,Internal medicine ,medicine ,Humans ,Sports and Exercise Medicine ,Exercise ,Cardiac Muscles ,Pulmonary Gas Exchange ,business.industry ,Biology and Life Sciences ,Physical Activity ,030229 sport sciences ,Muscle oxygenation ,Oxygen ,Skeletal Muscles ,Physical Fitness ,Physiological Processes ,business - Abstract
Cardiovascular adaptations to exercise, particularly at the individual level, remain poorly understood. Previous group level research suggests the relationship between cardiac output and oxygen consumption ([Formula: see text]-[Formula: see text]) is unaffected by training as submaximal [Formula: see text] is unchanged. We recently identified substantial inter-individual variation in the exercise [Formula: see text]-[Formula: see text] relationship that was correlated to stroke volume (SV) as opposed to arterial oxygen content. Therefore we explored the effects of sprint interval training (SIT) on modulating [Formula: see text]-[Formula: see text] given an individual's specific [Formula: see text]-[Formula: see text] relationship. 22 (21±2 yrs) healthy, recreationally active males participated in a 4-week SIT (8, 20 second sprints; 4x/week, 170% of the work rate at [Formula: see text] peak) study with progressive exercise tests (PET) until exhaustion. Cardiac output ([Formula: see text] L/min; inert gas rebreathe, Finometer Modelflow™), oxygen consumption ([Formula: see text] L/min; breath-by-breath pulmonary gas exchange), quadriceps oxygenation (near infrared spectroscopy) and exercise tolerance (6-20; Borg Scale RPE) were measured throughout PET both before and after training. Data are mean Δ from bsl±SD. Higher [Formula: see text] ([Formula: see text]) and lower [Formula: see text] ([Formula: see text]) responders were identified post hoc (n = 8/group). SIT increased the [Formula: see text]-[Formula: see text] post-training in [Formula: see text] (3.8±0.2 vs. 4.7±0.2; P = 0.02) while [Formula: see text] was unaffected (5.8±0.1 vs. 5.3±0.6; P = 0.5). [Formula: see text] was elevated beyond 80 watts in [Formula: see text] due to a greater increase in SV (all P0.1). In contrast to [Formula: see text], [Formula: see text] responders are capable of improving submaximal [Formula: see text]-[Formula: see text] in response to SIT via increased SV. However, the increased submaximal exercise [Formula: see text] does not benefit exercising muscle oxygenation.
- Published
- 2019
34. A 56-Year-Old, Otherwise Healthy Woman Presenting With Light-headedness and Progressive Shortness of Breath
- Author
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Daniel M. Hirai, Danilo C. Berton, Joel T. Zelt, Joshua H. Jones, J. Alberto Neder, and Denis E. O'Donnell
- Subjects
Pulmonary and Respiratory Medicine ,Pediatrics ,medicine.medical_specialty ,Light-headedness ,Lightheadedness ,Referral ,Psychological Techniques ,Critical Care and Intensive Care Medicine ,Dizziness ,Breast cysts ,Diagnosis, Differential ,03 medical and health sciences ,0302 clinical medicine ,Quality of life ,medicine ,Humans ,Hyperventilation ,030212 general & internal medicine ,Prolactinoma ,Presyncope ,Past medical history ,business.industry ,Yoga ,Middle Aged ,medicine.disease ,Respiratory Function Tests ,Dyspnea ,Treatment Outcome ,030228 respiratory system ,Echocardiography ,Quality of Life ,Physical therapy ,Female ,medicine.symptom ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,business - Abstract
A 56-year-old white woman was referred to the pulmonary clinic for evaluation of unexplained shortness of breath. She enjoyed good health until 3 months prior to this visit when she reported experiencing recurrent episodes of shortness of breath and oppressive retrosternal chest discomfort with radiation to the neck. Episodes lasting 5 to 10 min often occurred at rest and were inconsistently related to physical activity. These symptoms became progressively worse and were often associated with light-headedness and presyncope. Her past medical history was uneventful apart from a prior diagnosis of breast cysts and suspected prolactinoma. Her symptoms escalated to such a level that she was forced to seek urgent medical attention at our institutional ED on two separate occasions in the preceding weeks. These visits precipitated a number of investigations and, eventually, a referral to the pulmonary clinic.
- Published
- 2016
35. ATP-sensitive K+ channel inhibition in rats decreases kidney and skeletal muscle blood flow without increasing sympathetic nerve discharge
- Author
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Shawnee Montgomery, Daniel M. Hirai, Clark T. Holdsworth, Michael J. Kenney, Jesse C. Craig, Timothy I. Musch, David C. Poole, and Trenton D. Colburn
- Subjects
Pulmonary and Respiratory Medicine ,Mean arterial pressure ,medicine.medical_specialty ,Sympathetic Nervous System ,Baroreceptor ,Physiology ,Pressoreceptors ,Hindlimb ,Article ,Renal Circulation ,Microcirculation ,Glibenclamide ,03 medical and health sciences ,Renal Artery ,0302 clinical medicine ,KATP Channels ,Internal medicine ,Glyburide ,medicine ,Animals ,Arterial Pressure ,Muscle, Skeletal ,Kidney ,Chemistry ,General Neuroscience ,Skeletal muscle ,Hyperpolarization (biology) ,Rats ,medicine.anatomical_structure ,Endocrinology ,030228 respiratory system ,Regional Blood Flow ,Vasoconstriction ,030217 neurology & neurosurgery ,medicine.drug - Abstract
ATP-sensitive K+ (KATP) channels contribute to exercise-induced hyperemia in skeletal muscle either locally by vascular hyperpolarization or by sympathoinhibition and decreased sympathetic vasoconstriction. However, mean arterial pressure (MAP) regulation via baroreceptors and subsequent efferent activity may confound assessment of vascular versus neural KATP channel function. We hypothesized that systemic KATP channel inhibition via glibenclamide (GLI) would increase MAP without increasing sympathetic nerve discharge (SND). Lumbar and renal nerve SND were measured in anesthetized male rats with intact baroreceptors (n = 12) and sinoaortic denervated (SAD; n = 4) counterparts and blood flow (BF) and vascular conductance (VC) assessed in conscious rats (n = 6). GLI increased MAP (p < 0.05) and transiently decreased HR in intact (p < 0.05), but not SAD rats. Renal (-30 %) and lumbar (-40 %) ΔSND decreased in intact but increased in SAD rats (∼40 % and 20 %; p < 0.05). BF and VC decreased in kidneys and total hindlimb skeletal muscle (p < 0.05). Thus, because KATP inhibition decreases SND, GLI-induced reductions in blood flow cannot result from enhanced sympathetic activity.
- Published
- 2020
36. Impact Of Cell-free Hemoglobin On Exercising Muscle Vascular Control In Rats
- Author
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David Irwin, K. S. Hageman, Paul W. Buehler, Timothy I. Musch, David C. Poole, Kurt R. Stenmark, Trenton D. Colburn, Daniel M. Hirai, Jesse C. Craig, and Scott K. Ferguson
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Cell free hemoglobin ,Internal medicine ,Medicine ,Physical Therapy, Sports Therapy and Rehabilitation ,Orthopedics and Sports Medicine ,business - Published
- 2020
37. Skeletal Muscle Capillary Hemodynamics in Rats with Heart Failure with Preserved Ejection Fraction
- Author
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Jesse C. Craig, Dryden R. Baumfalk, Alex B. Opoku-Acheampong, David C. Poole, K. Sue Hageman, Carl J. Ade, Daniel M. Hirai, Jacob T. Caldwell, Brad J. Behnke, Trenton D. Colburn, Timothy I. Musch, and Ayaka Tabuchi
- Subjects
medicine.medical_specialty ,business.industry ,Capillary action ,Hemodynamics ,Skeletal muscle ,Biochemistry ,medicine.anatomical_structure ,Internal medicine ,Genetics ,medicine ,Cardiology ,business ,Heart failure with preserved ejection fraction ,Molecular Biology ,Biotechnology - Published
- 2020
38. Regulation of Capillary Hemodynamics by K ATP Channels in Resting Skeletal Muscle
- Author
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Timothy I. Musch, Trenton D. Colburn, Daniel M. Hirai, Ayaka Tabuchi, Jesse C. Craig, K. Sue Hageman, and David C. Poole
- Subjects
0301 basic medicine ,Capillary action ,Chemistry ,Skeletal muscle ,Hemodynamics ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Genetics ,medicine ,Biophysics ,Molecular Biology ,030217 neurology & neurosurgery ,Biotechnology - Published
- 2018
39. Interstitial PO 2 Dynamics During Contractions in Healthy Skeletal Muscle: Relationship to Oxidative Capacity and Nitric Oxide Bioavailability
- Author
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Daniel M. Hirai, Trenton D. Colburn, David C. Poole, K. Sue Hageman, Ayaka Tabuchi, Jesse C. Craig, and Timothy I. Musch
- Subjects
medicine.medical_specialty ,Skeletal muscle ,Biochemistry ,Nitric oxide ,Bioavailability ,chemistry.chemical_compound ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Internal medicine ,Genetics ,medicine ,Oxidative capacity ,Molecular Biology ,Biotechnology - Published
- 2018
40. Systemic vascular dysfunction is associated with emphysema burden in mild COPD
- Author
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J. Alberto Neder, Joshua H. Jones, Trevor J. King, Joel T. Zelt, Danilo C. Berton, Daniel M. Hirai, Kyra E. Pyke, and Denis E. O'Donnell
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Vital Capacity ,Disease ,030204 cardiovascular system & hematology ,Pulse Wave Analysis ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Vascular Stiffness ,DLCO ,Risk Factors ,Internal medicine ,Forced Expiratory Volume ,medicine ,Humans ,Vascular Diseases ,Respiratory system ,Muscle, Skeletal ,Pulse wave velocity ,Aged ,COPD ,business.industry ,Oxygenation ,Blood flow ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Oxygen ,Vasodilation ,Forearm ,030228 respiratory system ,Pulmonary Emphysema ,Case-Control Studies ,Microvessels ,Cardiology ,Arterial stiffness ,Female ,business ,Tomography, X-Ray Computed - Abstract
Background Cardiovascular diseases play a major role in morbidity and mortality in the earlier stages of COPD. We hypothesized that systemic vascular dysfunction would be present even in patients who are currently considered at “low-risk” for negative cardiovascular outcomes, i.e., those with largely preserved FEV1, few exacerbations and only mild burden of respiratory symptoms (GOLD spirometric grade 1, clinical group A). Methods 16 patients (FEV1 = 86 ± 13%) and 16 age- and gender-matched controls underwent measurements of: a) central arterial stiffness by pulse wave velocity, b) brachial flow-mediated dilation and c) forearm muscle oxygenation by near-infrared spectroscopy. Computed tomography quantified emphysema (% of low attenuation areas (LAA)) and airway disease. Results Patients and controls were well matched for key clinical variables including co-morbidities burden. Thirteen patients presented with more than 5% LAA: emphysema extension was negatively related to transfer factor for carbon monoxide (TLCO) (r = −0.63; p = .01). Compared to controls, patients had higher central arterial stiffness, lower normalized (to shear stress) flow-mediated dilation, delayed time to peak flow-mediated dilation and poorer muscle oxygenation (p Conclusion Systemic vascular dysfunction is present in the earlier stages of COPD, particularly in patients with greater emphysema burden and low TLCO. Regardless FEV1, patients showing those structural and functional abnormalities might be at higher risk of negative events thereby deserving closer follow-up for early detection of cardiovascular disease.
- Published
- 2017
41. An Assessment of the Fuel Pulverization Threshold During LOCA-Type Temperature Transients
- Author
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C. T. Walker, J. A. Turnbull, M. Hirai, D. M. Staicu, and S. K. Yagnik
- Subjects
Materials science ,Nuclear Energy and Engineering ,Nuclear engineering ,Pellets ,Transient (oscillation) - Abstract
To investigate the potential disintegration to powder of high-burnup fuel pellets during a rapid temperature transient, the Nuclear Fuels Industry Research (NFIR) Program commissioned two independe...
- Published
- 2015
42. Exercise Intolerance in Pulmonary Arterial Hypertension. The Role of Cardiopulmonary Exercise Testing
- Author
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Daniel M. Hirai, Denis E. O'Donnell, Jaquelina S. Ota-Arakaki, J. Alberto Neder, Christine L. D’Arsigny, and Roberta Pulcheri Ramos
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Exercise Tolerance ,business.industry ,Hypertension, Pulmonary ,Physical Exertion ,Cardiopulmonary exercise testing ,Exercise intolerance ,Heart Septal Defects, Atrial ,Young Adult ,Dyspnea ,Internal medicine ,Exercise Test ,Cardiology ,Humans ,Medicine ,Female ,medicine.symptom ,business - Published
- 2015
43. Oxygen delivery-utilization mismatch in contracting locomotor muscle in COPD: peripheral factors
- Author
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Denis E. O'Donnell, Diogo P. Azevedo, Daniel M. Hirai, Wladimir Musetti Medeiros, Flavia Fernandes Manfredi de Freitas, Beatriz C. Amorim, Mari C. T. Fernandes, Luciana Dias Chiavegato, J. Alberto Neder, Universidade Federal de São Paulo (UNIFESP), and Queens Univ
- Subjects
Male ,medicine.medical_specialty ,near-infrared spectroscopy ,Physiology ,neuromuscular electrical stimulation ,torque ,chronic obstructive pulmonary disease ,Pulmonary Disease, Chronic Obstructive ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,skeletal muscle ,Muscle, Skeletal ,Exercise ,Aged ,Aged, 80 and over ,COPD ,exercise ,Myoglobin ,Pulmonary Gas Exchange ,Chemistry ,Skeletal muscle ,Cardiorespiratory fitness ,Oxygenation ,Middle Aged ,medicine.disease ,Peripheral ,Oxygen ,medicine.anatomical_structure ,Ambulatory ,Cardiology ,Physical therapy ,Oxygen delivery ,Whole body ,Muscle Contraction - Abstract
Central cardiorespiratory and gas exchange limitations imposed by chronic obstructive pulmonary disease (COPD) impair ambulatory skeletal muscle oxygenation during whole body exercise. This investigation tested the hypothesis that peripheral factors per se contribute to impaired contracting lower limb muscle oxygenation in COPD patients. Submaximal neuromuscular electrical stimulation (NMES; 30, 40, and 50 mA at 50 Hz) of the quadriceps femoris was employed to evaluate contracting skeletal muscle oxygenation while minimizing the influence of COPD-related central cardiorespiratory constraints. Fractional O-2 extraction was estimated by near-infrared spectroscopy (deoxyhemoglobin/myoglobin concentration; deoxy-[Hb/Mb]), and torque output was measured by isokinetic dynamometry in 15 nonhypoxemic patients with moderate-to-severe COPD (SpO(2) = 94 +/- 2%; FEV1 = 46.4 +/- 10.1%; GOLD II and III) and in 10 age- and gender-matched sedentary controls. COPD patients had lower leg muscle mass than controls (LMM = 8.0 +/- 0.7 kg vs. 8.9 +/- 1.0 kg, respectively; P < 0.05) and produced relatively lower absolute and LMM-normalized torque across the range of NMES intensities (P < 0.05 for all). Despite producing less torque, COPD patients had similar deoxy-[Hb/Mb] amplitudes at 30 and 40 mA (P > 0.05 for both) and higher deoxy-[Hb/Mb] amplitude at 50 mA (P < 0.05). Further analysis indicated that COPD patients required greater fractional O-2 extraction to produce torque (i.e., up arrow Delta deoxy-[Hb/Mb]/torque) relative to controls (P < 0.05 for 40 and 50 mA) and as a function of NMES intensity (P < 0.05 for all). the present data obtained during sub-maximal NMES of small muscle mass indicate that peripheral abnormalities contribute mechanistically to impaired contracting skeletal muscle oxygenation in nonhypoxemic, moderate-to-severe COPD patients. Universidade Federal de São Paulo, Sch Med, Dept Med, Div Resp,Pulm Funct & Clin Exercise Physiol Unit, São Paulo, Brazil Queens Univ, Dept Med, Div Resp & Crit Care Med, Lab Clin Exercise Physiol LACEP, Kingston, ON K7L 2V6, Canada Queens Univ, Dept Med, Div Resp & Crit Care Med, RIU, Kingston, ON K7L 2V6, Canada Universidade Federal de São Paulo, Sch Med, Dept Med, Div Resp,Pulm Funct & Clin Exercise Physiol Unit, São Paulo, Brazil Web of Science
- Published
- 2015
44. Insights into ventilation–gas exchange coupling in chronic thromboembolic pulmonary hypertension
- Author
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Danilo C. Berton, Christine L. D’Arsigny, Denis E. O'Donnell, Maria Clara Alencar, Eloara M. V. Ferreira, J. Alberto Neder, Priscila A. Sperandio, Flavio F. Arbex, Jaquelina S. Ota-Arakaki, Daniel M. Hirai, and Roberta Pulcheri Ramos
- Subjects
Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Exercise Tolerance ,Pulmonary Gas Exchange ,business.industry ,Hypertension, Pulmonary ,030204 cardiovascular system & hematology ,medicine.disease ,Pulmonary hypertension ,Exercise ventilation ,Pulmonary embolism ,03 medical and health sciences ,0302 clinical medicine ,030228 respiratory system ,Internal medicine ,Breathing ,Cardiology ,Humans ,Medicine ,Chronic thromboembolic pulmonary hypertension ,Pulmonary Embolism ,Pulmonary Ventilation ,business ,Intensive care medicine - Abstract
Increased “wasted” ventilation and heightened neural drive explains excess exercise ventilation in CTEPH http://ow.ly/Z4YBc
- Published
- 2016
45. Skeletal muscle microvascular and interstitial PO2 from rest to contractions
- Author
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Daniel M, Hirai, Jesse C, Craig, Trenton D, Colburn, Hiroaki, Eshima, Yutaka, Kano, William L, Sexton, Timothy I, Musch, and David C, Poole
- Subjects
Male ,Oxygen ,Rats, Sprague-Dawley ,Muscle Cells ,Oxygen Consumption ,Journal Club ,Rest ,Microvessels ,Animals ,Muscle, Skeletal ,Muscle Contraction ,Rats - Abstract
Oxygen pressure gradients across the microvascular walls are essential for oxygen diffusion from blood to tissue cells. At any given flux, the magnitude of these transmural gradients is proportional to the local resistance. The greatest resistance to oxygen transport into skeletal muscle is considered to reside in the short distance between red blood cells and myocytes. Although crucial to oxygen transport, little is known about transmural pressure gradients within skeletal muscle during contractions. We evaluated oxygen pressures within both the skeletal muscle microvascular and interstitial spaces to determine transmural gradients during the rest-contraction transient in anaesthetized rats. The significant transmural gradient observed at rest was sustained during submaximal muscle contractions. Our findings support that the blood-myocyte interface provides substantial resistance to oxygen diffusion at rest and during contractions and suggest that modulations in microvascular haemodynamics and red blood cell distribution constitute primary mechanisms driving increased transmural oxygen flux with contractions.Oxygen pressure (PO2) gradients across the blood-myocyte interface are required for diffusive O
- Published
- 2017
46. Skeletal muscle microvascular oxygenation dynamics in heart failure: exercise training and nitric oxide-mediated function
- Author
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Clark T. Holdsworth, Steven W. Copp, David C. Poole, Danielle J. McCullough, Daniel M. Hirai, Scott K. Ferguson, Timothy I. Musch, and Bradley J. Behnke
- Subjects
Male ,medicine.medical_specialty ,Physiology ,Vascular Biology and Microcirculation ,Nitric Oxide ,Ventricular Function, Left ,Nitric oxide ,Microcirculation ,Rats, Sprague-Dawley ,chemistry.chemical_compound ,Oxygen Consumption ,Physiology (medical) ,Internal medicine ,Ventricular Pressure ,medicine ,Animals ,Nitric Oxide Donors ,Myocardial infarction ,Enzyme Inhibitors ,Muscle, Skeletal ,Heart Failure ,biology ,business.industry ,Skeletal muscle ,Stroke Volume ,Oxygenation ,medicine.disease ,Adaptation, Physiological ,Exercise Therapy ,Rats ,Oxygen ,Nitric oxide synthase ,Disease Models, Animal ,Kinetics ,Endocrinology ,medicine.anatomical_structure ,chemistry ,Heart failure ,Physical Endurance ,biology.protein ,Nitric Oxide Synthase ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,Muscle Contraction ,Muscle contraction - Abstract
Chronic heart failure (CHF) impairs nitric oxide (NO)-mediated regulation of skeletal muscle O2 delivery-utilization matching such that microvascular oxygenation falls faster (i.e., speeds PO2 mv kinetics) during increases in metabolic demand. Conversely, exercise training improves (slows) muscle PO2 mv kinetics following contractions onset in healthy young individuals via NO-dependent mechanisms. We tested the hypothesis that exercise training would improve contracting muscle microvascular oxygenation in CHF rats partly via improved NO-mediated function. CHF rats (left ventricular end-diastolic pressure = 17 ± 2 mmHg) were assigned to sedentary (n = 11) or progressive treadmill exercise training (n = 11; 5 days/wk, 6–8 wk, final workload of 60 min/day at 35 m/min; −14% grade downhill running) groups. PO2 mv was measured via phosphorescence quenching in the spinotrapezius muscle at rest and during 1-Hz twitch contractions under control (Krebs-Henseleit solution), sodium nitroprusside (SNP; NO donor; 300 μM), and NG-nitro-l-arginine methyl ester (L-NAME, nonspecific NO synthase blockade; 1.5 mM) superfusion conditions. Exercise-trained CHF rats had greater peak oxygen uptake and spinotrapezius muscle citrate synthase activity than their sedentary counterparts ( p < 0.05 for both). The overall speed of the PO2 mv fall during contractions (mean response time; MRT) was slowed markedly in trained compared with sedentary CHF rats (sedentary: 20.8 ± 1.4, trained: 32.3 ± 3.0 s; p < 0.05), and the effect was not abolished by L-NAME (sedentary: 16.8 ± 1.5, trained: 31.0 ± 3.4 s; p > 0.05). Relative to control, SNP increased MRT in both groups such that trained CHF rats had slower kinetics (sedentary: 43.0 ± 6.8, trained: 55.5 ± 7.8 s; p < 0.05). Improved NO-mediated function is not obligatory for training-induced improvements in skeletal muscle microvascular oxygenation (slowed PO2 mv kinetics) following contractions onset in rats with CHF.
- Published
- 2014
47. Effects of Pentoxifylline on Exercising Skeletal Muscle Vascular Control in Rats with Chronic Heart Failure
- Author
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Clark T. Holdsworth, Scott K. Ferguson, Timothy I. Musch, Gabrielle E. Sims, Daniel M. Hirai, David C. Poole, and Steven W. Copp
- Subjects
medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Skeletal muscle ,Exercise intolerance ,Hindlimb ,medicine.disease ,Surgery ,Pentoxifylline ,medicine.anatomical_structure ,Internal medicine ,Heart failure ,medicine ,Cardiology ,cardiovascular diseases ,Myocardial infarction ,Treadmill ,medicine.symptom ,business ,Saline ,medicine.drug - Abstract
Purpose : Chronic heart failure (CHF) is hallmarked by cardiac and peripheral vasculature dysfunction which has been associated with elevations in tumor necrosis factor-α (TNF-α) and exercise intolerance. The pharmaceutical TNF-α synthesis suppressor pentoxifylline (PTX) reduces plasma [TNF-α] and improves left ventricular (LV) function in CHF rats, but the effects of PTX on skeletal muscle blood flow (BF) and vascular conductance (VC) during exercise are unknown. We tested the hypothesis that PTX would elevate skeletal muscle BF and VC at rest and during submaximal treadmill exercise in CHF rats and improve exercise tolerance and peak O 2 uptake. Methods : CHF rats (coronary artery ligation) received i.p. injections of 30 mg·kg -1 ·day -1 of PTX (CHF+PTX, n=13) or saline (CHF, n=8) for 21 days. BF was measured using radiolabeled microspheres at rest and during exercise (treadmill, 20 m/min -1 , 5% grade). Results : Resting and exercising mean arterial pressures (MAP) were greater in CHF+PTX compared to CHF (i.e., closer to expected healthy values, both p
- Published
- 2014
48. Emphysema on Thoracic CT and Exercise Ventilatory Inefficiency in Mild-to-Moderate COPD
- Author
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J. Alberto Neder, Daniel M. Hirai, Denis E. O'Donnell, Camilla V Diniz, Joshua H. Jones, Joel T. Zelt, and Aida Zaza
- Subjects
Pulmonary and Respiratory Medicine ,Male ,medicine.medical_specialty ,Pulmonary Circulation ,030204 cardiovascular system & hematology ,Severity of Illness Index ,Incremental exercise ,03 medical and health sciences ,Pulmonary Disease, Chronic Obstructive ,0302 clinical medicine ,Oxygen Consumption ,DLCO ,Diffusing capacity ,Internal medicine ,medicine ,Humans ,Prospective Studies ,Exercise ,Aged ,COPD ,Lung ,Exercise Tolerance ,business.industry ,Pulmonary Gas Exchange ,VO2 max ,Carbon Dioxide ,Middle Aged ,medicine.disease ,Obstructive lung disease ,respiratory tract diseases ,Surgery ,medicine.anatomical_structure ,Dyspnea ,030228 respiratory system ,Pulmonary Emphysema ,Case-Control Studies ,Cardiology ,Breathing ,Exercise Test ,Female ,Radiography, Thoracic ,business ,Pulmonary Ventilation ,Tomography, X-Ray Computed - Abstract
There is growing evidence that emphysema on thoracic computed tomography (CT) is associated with poor exercise tolerance in COPD patients with only mild-to-moderate airflow obstruction. We hypothesized that an excessive ventilatory response to exercise (ventilatory inefficiency) would underlie these abnormalities. In a prospective study, 19 patients (FEV1 = 82 ± 13%, 12 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage 1) and 26 controls underwent an incremental exercise test. Ventilatory inefficiency was assessed by the ventilation ([Formula: see text]E)/CO2 output ([Formula: see text]CO2) nadir. Pulmonary blood flow (PBF) in a submaximal test was calculated by inert gas rebreathing. Emphysema was quantified as % of attenuation areas below 950 HU. Patients typically presented with centrilobular emphysema (76.8 ± 10.1% of total emphysema) in the upper lobes (upper/total lung ratio = 0.82 ± 0.04). They had lower peak oxygen uptake ([Formula: see text]O2), higher [Formula: see text]E/[Formula: see text]CO2 nadir, and greater dyspnea scores than controls (p < 0.05). Lower peak [Formula: see text]O2 and worse dyspnea were found in patients with higher [Formula: see text]E/[Formula: see text]CO2 nadirs (≥30). Patients had blunted increases in PBF from rest to iso-[Formula: see text]O2 exercise (p < 0.05). Higher [Formula: see text]E/[Formula: see text]CO2 nadir in COPD was associated with emphysema severity (r = 0.63) which, in turn, was related to reduced lung diffusing capacity (r = -0.72) and blunted changes in PBF from rest to exercise (r = -0.69) (p < 0.01). Ventilation "wasted" in emphysematous areas is associated with impaired exercise ventilatory efficiency in mild-to-moderate COPD. Exercise ventilatory inefficiency links structure (emphysema) and function (DLCO) to a key clinical outcome (poor exercise tolerance) in COPD patients with only modest spirometric abnormalities.
- Published
- 2016
49. First Monte Carlo analysis of fragmentation functions from single-inclusivee+e−annihilation
- Author
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Wolodymyr Melnitchouk, Nobuo Sato, S. Kumano, Jacob J. Ethier, M. Hirai, and Alberto Accardi
- Subjects
Quark ,Physics ,Particle physics ,Strange quark ,Annihilation ,010308 nuclear & particles physics ,Electron–positron annihilation ,Nuclear Theory ,Monte Carlo method ,Fragmentation (computing) ,01 natural sciences ,Computer Science::Other ,Nuclear physics ,Pion ,0103 physical sciences ,Fragmentation function ,High Energy Physics::Experiment ,Nuclear Experiment ,010306 general physics - Abstract
We perform the first iterative Monte Carlo (IMC) analysis of fragmentation functions constrained by all available data from single-inclusive ${e}^{+}{e}^{\ensuremath{-}}$ annihilation into pions and kaons. The IMC method eliminates potential bias in traditional analyses based on single fits introduced by fixing parameters not well constrained by the data and provides a statistically rigorous determination of uncertainties. Our analysis reveals specific features of fragmentation functions using the new IMC methodology and those obtained from previous analyses, especially for light quarks and for strange quark fragmentation to kaons.
- Published
- 2016
50. Oral
- Author
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Daniel M, Hirai, Joshua H, Jones, Joel T, Zelt, Marianne L, da Silva, Robert F, Bentley, Brittany A, Edgett, Brendon J, Gurd, Michael E, Tschakovsky, Denis E, O'Donnell, and J Alberto, Neder
- Subjects
Male ,Cross-Over Studies ,Exercise Tolerance ,Hemodynamics ,Antioxidants ,Acetylcysteine ,Respiratory Function Tests ,Oxygen ,Pulmonary Disease, Chronic Obstructive ,Double-Blind Method ,Humans ,Female ,Muscle, Skeletal ,Exercise ,Locomotion ,Aged - Abstract
Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with
- Published
- 2016
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