23 results on '"Padilla DJ"'
Search Results
2. Effect of furosemide and the equine nasal strip on exercise-induced pulmonary haemorrhage and time-to-fatigue in maximally exercising horses
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Poole, DC, primary, McDonough, P, additional, Kindig, CA, additional, Hildreth, TS, additional, Padilla, DJ, additional, Behnke, BJ, additional, Erickson, HH, additional, and Poole, DC, additional
- Published
- 2004
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3. The effect of herbal supplementation on the severity of exercise-induced pulmonary haemorrhage.
- Author
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Epp, TS, McDonough, P, Padilla, DJ, Cox, JH, Poole, DC, and Erickson, HH
- Abstract
Exercise-induced pulmonary haemorrhage (EIPH) is a serious condition that affects the health and possibly the performance of all racehorses. However, only two treatments, furosemide and the Flair™ equine nasal strip, both of which reduce capillary transmural pressure, have been successful in reducing EIPH. Alternatively, transient impairment of platelet function and coagulation during exercise has been considered an additional contributor to EIPH. Consequently, herbal formulations designed to enhance platelet function, and hence coagulation, are hypothesized to reduce EIPH. To investigate the validity of this hypothesis, five Thoroughbred horses completed three maximal incremental exercise tests on a 10% inclined treadmill in a randomized cross-over design experiment. Treatments included twice daily oral administration (for 3 days) of a placebo (PL; cornstarch) and two herbal formulas, Yunnan Paiyao (YP) or Single Immortal (SI). Blood samples for coagulation profiles, complete blood counts and biochemistry profiles were collected before each exercise test. During each test, pulmonary arterial pressure, oxygen uptake, arterial blood gases, plasma lactate and time-to-fatigue were measured. Severity of EIPH was quantified via bronchoalveolar lavage (BAL) at 30–60 min post-exercise. The herbal formulations were not effective in decreasing EIPH (×106 red blood cells ml−1 BAL fluid: PL, 27.1±11.6; YP, 33.2±23.4; SI, 35.3±15.4, P>0.05) or in changing any of the other variables measured with the exception of time-to-fatigue, which was slightly but significantly prolonged by Single Immortal compared with placebo and Yunnan Paiyao (PL, 670±9.6 s; YP, 665±5.5 s; SI, 685±7.9 s, P<0.05). Thus, these results do not support the use of these herbal formulations in the prevention of EIPH. [ABSTRACT FROM PUBLISHER]
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- 2004
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4. Effect of furosemide and the equine nasal strip on exercise-induced pulmonary haemorrhage and time-to-fatigue in maximally exercising horses.
- Author
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McDonough, P, Kindig, CA, Hildreth, TS, Padilla, DJ, Behnke, BJ, Erickson, HH, and Poole, DC
- Abstract
Furosemide (FUR) and the equine nasal strip (NS) decrease exercise-induced pulmonary haemorrhage (EIPH) compared with control (CON) conditions in the Thoroughbred horse during near-maximal running trials. As FUR and NS have potential performance-enhancing properties, we studied Thoroughbreds running to fatigue to test the hypothesis that time-to-fatigue (TTF) would be increased, yet EIPH reduced, in FUR and NS compared with CON. Thoroughbred geldings (n=6) were run to volitional fatigue on a level treadmill (1 m s−1 increment per minute from an initial trot) every two weeks (order randomized) under CON, NS, FUR (1 mg kg−1; 4 h prior) and FUR+NS conditions. Pulmonary arterial pressure (Ppa) and pulmonary gas exchange were measured throughout exercise, while arterial blood gases were sampled at the end of each 1-min stage. EIPH severity was quantified via bronchoalveolar lavage (BAL) at 30 min post-exercise. TTF was increased for all experimental conditions (i.e. an additional 20±13, 28±8 and 40±6 s for NS, FUR and FUR+NS, respectively; P<0.05) compared with CON. Peak mean Ppa was significantly reduced (P<0.05) for FUR (93.6±6.3 mmHg) and FUR+ NS (95.4±5.1 mmHg), yet unchanged with NS (98.0±5.8 mmHg; P>0.05) compared with CON (100.5±4.9 mmHg). All three experimental conditions exhibited a significant reduction in EIPH compared with CON (64.1±36.8× 6 red blood cells (RBCs) ml−1); however, no significant difference was noted between these conditions (×106 RBCs ml−1: 29.1±16.8, 20.9±13.1 and 26.7±19.8 for NS, FUR and FUR+NS, respectively). Furthermore, no differences for either end-exercise cardiorespiratory (i.e. V˙O2 or V˙CO2) or blood-borne metabolic (i.e. blood gases, lactate or pH) variables were observed. These findings demonstrate that both FUR and NS enhance TTF and reduce EIPH to a similar degree during high-speed treadmill running to fatigue. [ABSTRACT FROM PUBLISHER]
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- 2004
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5. Abusing the Fick principle.
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Padilla DJ, Musch TI, and Poole DC
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- 2005
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6. Standardized intrapulmonary lymph node dissection in lung cancer specimens: A national Colombian analysis.
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Mantilla Gaviria HJ, Martinez Jaramillo SI, Carvajal Fierro CA, Zapata González RA, Montoya Medina C, Garcia-Herreros Hellal LG, Tellez Rodriguez LJ, Garzon Ramírez JC, Padilla Padilla DJ, Correa Solano AA, Barrios Del Rio R, Peláez Arango M, Castaño Ruiz W, Zerrate Misas A, Velásquez Gómez L, Beltrán Jiménez RJ, Buitrago Ramírez MR, Jimenez Quijano JAE, Mendivelso Duarte FO, and Ugalde Figueroa PA
- Abstract
Objective: In patients with non-small cell lung cancer, lymph node assessment is essential for appropriate staging. The intrapulmonary lymph nodes (IPLNs) should be considered when assigning the N stage but are infrequently evaluated in Colombian centers, resulting in understaging that may hinder optimal treatment., Methods: We conducted a prospective study of IPLN dissection in patients with clinical stage I or II non-small cell lung cancer who underwent surgical resection at 9 institutions in Colombia between 2021 and 2023. IPLN dissection was performed by trained surgeons who collected lymph nodes from fresh specimens after resection and before formalin fixation., Results: One hundred patients were eligible for the analysis. Their mean age was 67 ± 10.9 years, and 76% were women. Most (74%) had adenocarcinoma, 20% had neuroendocrine tumors, and 6% had squamous cell carcinoma. Successful sampling and histopathologic analysis of at least one IPLN station was obtained in 85% of patients, 9% had upstaging due to positive N2 lymph nodes, and 5% had upstaging due to positive N1 lymph nodes. Among the patients with pN0 or pN1 disease, 3.2% (3 out of 91) were upstaged exclusively due to positive IPLNs., Conclusions: Fresh-specimen dissection to collect IPLNs is appropriate and feasible to achieve more accurate pathological staging in Colombian lung cancer patients. In clinical N0 patients, IPLN dissection maximizes selection for adjuvant therapy., Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflict of interest., (© 2024 The Author(s).)
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- 2024
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7. Plasticity of microvascular oxygenation control in rat fast-twitch muscle: effects of experimental creatine depletion.
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McDonough P, Padilla DJ, Kano Y, Musch TI, Poole DC, and Behnke BJ
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- Animals, Creatine drug effects, Muscle, Skeletal physiology, Oxygen metabolism, Phosphocreatine drug effects, Rats, Creatine metabolism, Guanidines pharmacology, Microcirculation drug effects, Muscle Contraction drug effects, Muscle Fibers, Fast-Twitch drug effects, Oxygen Consumption, Phosphocreatine metabolism, Propionates pharmacology
- Abstract
Aging, heart failure and diabetes each compromise the matching of O2 delivery (Q˙O2)-to-metabolic requirements (O2 uptake, V˙O2) in skeletal muscle such that the O2 pressure driving blood-myocyte O2 flux (microvascular PO2, PmvO2) is reduced and contractile function impaired. In contrast, β-guanidinopropionic acid (β-GPA) treatment improves muscle contractile function, primarily in fast-twitch muscle (Moerland and Kushmerick, 1994). We tested the hypothesis that β-GPA (2% wt/BW in rat chow, 8 weeks; n=14) would improve Q˙O2-to-V˙O2 matching (elevated PmvO2) during contractions (4.5V @ 1Hz) in mixed (MG) and white (WG) portions of the gastrocnemius, both predominantly fast-twitch). Compared with control (CON), during contractions PmvO2 fell less following β-GPA (MG -54%, WG -26%, P<0.05), elevating steady-state PmvO2 (CON, MG: 10±2, WG: 9±1; β-GPA, MG 16±2, WG 18±2 mmHg, P<0.05). This reflected an increased Q˙O2/V˙O2 ratio due primarily to a reduced V˙O2 in β-GPA muscles. It is likely that this adaptation helps facilitate the β-GPA-induced enhancement of contractile function in fast-twitch muscles., (Copyright © 2012 Elsevier B.V. All rights reserved.)
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- 2012
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8. Comparison of glass fragments using particle-induced X-ray emission (PIXE) spectrometry.
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DeYoung PA, Hall CC, Mears PJ, Padilla DJ, Sampson R, and Peaslee GF
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A procedure has been developed to analyze the trace element concentrations in glass fragments using particle-induced X-ray emission (PIXE) spectrometry. This method involves using accelerated protons to excite inner-shell electronic transitions of target atoms and recording the resultant X-rays to characterize the trace element concentrations. The protocol was able to identify those glass fragments that originated from different sources based on their elemental analyses. The protocol includes specific approaches to calculating uncertainties and handling measurements below the level of detection. The results indicate that this approach has increased sensitivity for several elements with higher atomic number compared with X-ray fluorescence methods. While not as sensitive as laser-ablation or inductively coupled plasma mass spectrometry methods of dissolved samples, it is entirely nondestructive and entails a much simpler sample preparation process that may be used to presort glass fragments for more comprehensive elemental analysis. As such, the technique described may have a niche role in forensic glass analysis., (© 2011 American Academy of Forensic Sciences.)
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- 2011
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9. Formulation and pharmacokinetics of self-assembled rifampicin nanoparticle systems for pulmonary delivery.
- Author
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Sung JC, Padilla DJ, Garcia-Contreras L, Verberkmoes JL, Durbin D, Peloquin CA, Elbert KJ, Hickey AJ, and Edwards DA
- Subjects
- Animals, Antitubercular Agents administration & dosage, Guinea Pigs, Lactic Acid, Polyglycolic Acid, Polylactic Acid-Polyglycolic Acid Copolymer, Rifampin administration & dosage, Antitubercular Agents chemistry, Antitubercular Agents pharmacokinetics, Chemistry, Pharmaceutical, Nanoparticles, Rifampin chemistry, Rifampin pharmacokinetics
- Abstract
Purpose: To formulate rifampicin, an anti-tuberculosis antibiotic, for aerosol delivery in a dry powder 'porous nanoparticle-aggregate particle' (PNAP) form suited for shelf stability, effective dispersibility and extended release with local lung and systemic drug delivery., Methods: Rifampicin was encapsulated in PLGA nanoparticles by a solvent evaporation process, spray dried into PNAPs containing varying amounts of nanoparticles, and characterized for physical and aerosol properties. Pharmacokinetic studies were performed with formulations delivered to guinea pigs by intratracheal insufflation and compared to oral and intravenous delivery of rifampicin., Results: The PNAP formulations possessed properties suitable for efficient deposition in the lungs. In vitro release showed an initial burst of rifampicin, with the remainder available for release beyond eight hours. PNAPs delivered to guinea pigs by insufflation achieved systemic levels of rifampicin detected for six to eight hours. Moreover, rifampicin concentrations remained detectable in lung tissue and cells up to and beyond eight hours. Conversely, after pulmonary delivery of an aerosol without nanoparticles, rifampicin could not be detected in the lungs at eight hours., Conclusions: Our results indicate that rifampicin can be formulated into an aggregated nanoparticle form that, once delivered to animals, achieves systemic exposure and extends levels of drug in the lungs.
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- 2009
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10. Control of microvascular oxygen pressures during recovery in rat fast-twitch muscle of differing oxidative capacity.
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McDonough P, Behnke BJ, Padilla DJ, Musch TI, and Poole DC
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- Animals, Luminescent Measurements, Rats, Regional Blood Flow physiology, Microcirculation physiology, Muscle Contraction physiology, Muscle Fibers, Fast-Twitch physiology, Muscle, Skeletal blood supply, Muscle, Skeletal physiology, Oxygen blood, Oxygen Consumption physiology
- Abstract
Whether the speed of recovery of microvascular O(2) pressures (Pmvo(2) ) differs within muscles composed primarily of type II fibres with contrasting oxidative capacity has not been determined. We tested the hypothesis that, following contractions, the recovery of Pmvo(2) would be slower in the white (WG; low oxidative capacity) versus the mixed gastrocnemius (MG; comparatively high oxidative capacity). Radiolabelled microsphere and phosphorescence quenching techniques were used to measure muscle blood flow ( Q, hence O(2) delivery, Q(O2)) and during contractions (1 Hz twitch) at low (LO, 2.5 V) and high intensities (HI, 4.5 V) in rat (n = 15) MG and WG muscle and during subsequent recovery. Following the LO protocol, end-contraction Pmvo(2) was lower in WG (11.6 +/- 0.5 mmHg) than in MG (16.2 +/- 0.6 mmHg; P < 0.05) while, contrary to our hypothesis, the initial rate of change in during recovery ( d P(O2)/dt; MG 0.11 +/- 0.01 mmHg s(-1) and WG 0.06 +/- 0.03 mmHg s(-1)) and mean response time (MRT; MG 110.3 +/- 5.1 s and WG 113.5 +/- 8.4 s, P > 0.05) were not different. In contrast, end-contraction baseline Pmvo(2) was not different following the HI protocol (MG 10.3 +/- 0.6 mmHg and WG 9.2 +/- 0.6 mmHg; P > 0.05) but, in agreement with our hypothesis, d P(O2)/dt was slower (MG 0.07 +/- 0.01 mmHg s(-1) and WG 0.03 +/- 0.003 mmHg s(-1); P < 0.05) and MRT longer (WG 180.8 +/- 4.5 s and MG 115.4 +/- 6.7 s; P < 0.05) in WG versus MG following the HI protocol. These data suggest that following high-intensity, though submaximal, muscle contractions, Pmvo(2) recovers much faster in the more oxidative mixed gastrocnemius than in the less oxidative white gastrocnemius.
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- 2007
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11. Effects of Type II diabetes on muscle microvascular oxygen pressures.
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Padilla DJ, McDonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, and Poole DC
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- Analysis of Variance, Animals, Capillaries metabolism, Disease Models, Animal, Male, Models, Biological, Muscle Contraction physiology, Muscle, Skeletal blood supply, Oxygen Consumption physiology, Rats, Rats, Inbred Strains, Rats, Wistar, Statistics, Nonparametric, Diabetes Mellitus, Type 2 blood, Glucose Intolerance blood, Muscle, Skeletal metabolism, Oxygen blood, Physical Conditioning, Animal physiology
- Abstract
We tested the hypothesis that muscle microvascular O2 pressure (PmvO2; reflecting the O2 delivery (QO2) to O2 uptake (VO2) ratio) would be lowered in the spinotrapezius muscle of Goto-Kakizaki (GK) Type II diabetic rats (n=7) at rest and during twitch contractions when compared to control (CON; n=5) rats. At rest, PmvO2 was lower in GK versus CON rats (CON: 29+/-2; GK: 18+/-2Torr; P<0.05). At the onset of contractions, GK rats evidenced a faster change in PmvO2 than CON (i.e., time constant (tau); CON: 16+/-4; GK: 6+/-2s; P<0.05). In contrast to the monoexponential fall in PmvO2 to the steady-state level seen in CON, GK rats exhibited a biphasic PmvO2 response that included a blunted (or non-existent) PmvO2 decrease followed by recovery to a steady-state PmvO2 that was at, or slightly above, resting values. Compared with CON, this decreased PmvO2 across the transition to a higher metabolic rate in Type II diabetes would be expected to impair blood-muscle O2 exchange and contractile function.
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- 2007
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12. Effects of Type II diabetes on capillary hemodynamics in skeletal muscle.
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Padilla DJ, McDonough P, Behnke BJ, Kano Y, Hageman KS, Musch TI, and Poole DC
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- Animals, Blood Glucose analysis, Blood Pressure, Diabetes Mellitus, Type 2 genetics, Disease Models, Animal, Erythrocytes physiology, Heart Rate, Hematocrit, Male, Microcirculation, Muscle, Skeletal pathology, Muscle, Skeletal physiopathology, Oxygen blood, Rats, Rats, Inbred Strains, Rats, Wistar, Regional Blood Flow, Capillaries physiology, Diabetes Mellitus, Type 2 physiopathology, Muscle, Skeletal blood supply, Muscle, Skeletal physiology
- Abstract
Microcirculatory red blood cell (RBC) hemodynamics are impaired within skeletal muscle of Type I diabetic rats (Kindig CA, Sexton WL, Fedde MR, and Poole DC. Respir Physiol 111: 163-175, 1998). Whether muscle microcirculatory dysfunction occurs in Type II diabetes, the more prevalent form of the disease, is unknown. We hypothesized that Type II diabetes would reduce the proportion of capillaries supporting continuous RBC flow and RBC hemodynamics within the spinotrapezius muscle of the Goto-Kakizaki Type II diabetic rat (GK). With the use of intravital microscopy, muscle capillary diameter (d(c)), capillary lineal density, capillary tube hematocrit (Hct(cap)), RBC flux (F(RBC)), and velocity (V(RBC)) were measured in healthy male Wistar (control: n = 5, blood glucose, 105 +/- 5 mg/dl) and male GK (n = 7, blood glucose, 263 +/- 34 mg/dl) rats under resting conditions. Mean arterial pressure did not differ between groups (P > 0.05). Sarcomere length was set to a physiological length ( approximately 2.7 mum) to ensure that muscle stretching did not alter capillary hemodynamics; d(c) was not different between control and GK rats (P > 0.05), but the percentage of RBC-perfused capillaries (control: 93 +/- 3; GK: 66 +/- 5 %), Hct(cap), V(RBC), F(RBC), and O(2) delivery per unit of muscle were all decreased in GK rats (P < 0.05). This study indicates that Type II diabetes reduces both convective O(2) delivery and diffusive O(2) transport properties within muscle microcirculation. If these microcirculatory deficits are present during exercise, it may provide a basis for the reduced O(2) exchange characteristic of Type II diabetic patients.
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- 2006
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13. Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability.
- Author
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Ferreira LF, Hageman KS, Hahn SA, Williams J, Padilla DJ, Poole DC, and Musch TI
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- Animals, Exercise Tolerance, Male, Microcirculation, Myocardial Infarction metabolism, NG-Nitroarginine Methyl Ester pharmacology, Nitric Oxide Synthase antagonists & inhibitors, Nitroprusside pharmacology, Rats, Rats, Sprague-Dawley, Vasodilator Agents pharmacology, Blood Vessels metabolism, Heart Failure metabolism, Muscle, Skeletal blood supply, Nitric Oxide metabolism, Oxygen metabolism
- Abstract
Aim: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO(2)'s (PO(2mv) proportional, variant O(2) delivery-to-uptake ratio) seen in healthy animals., Methods: We superfused sodium nitroprusside (SNP; 300 microm), Krebs-Henseleit (control, CON) and L-nitro arginine methyl ester (L-NAME; 1.5 mM) onto the spinotrapezius muscle and measured PO(2mv) by phosphorescence quenching in female Sprague-Dawley rats (n = 26) at rest and during twitch contractions (1 Hz). Seven rats served as controls (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as moderate (MOD; n = 15) and severe CHF (SEV; n = 4) according to morphological data and baseline PO(2mv)., Results: In contrast to Sham and MOD, L-NAME did not affect the PO(2mv) response (dynamics and steady-state) of SEV when compared with CON. SNP restored the PO(2mv) profile of SEV to that seen in Sham animals during CON. Specifically, the effect of L-NAME expressed as Delta(L-NAME - CON) were: Baseline PO(2mv) [in mmHg, DeltaSham = -7.0 +/- 1.6 (P < 0.05); DeltaSEV =-1.2 +/- 2.1], end-contractions PO(2mv) [in mmHg, DeltaSham = -5.0 +/- 1.0 (P < 0.05); DeltaSEV = -2.5 +/- 0.5] and time constant of PO(2mv) decrease [in s, DeltaSham = -6.5 +/- 3.0 (P < 0.05); DeltaSEV = -3.2 +/- 1.8]., Conclusion: These data provide the first direct evidence that the pathological profiles of PO(2mv) associated with severe CHF can be explained, in part, by a diminished vascular NO availability.
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- 2006
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14. Effects of a specific endothelin-1A antagonist on exercise-induced pulmonary haemorrhage (EIPH) in thoroughbred horses.
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Padilla DJ, Epp TS, McDonough P, Marlin DJ, Erickson HH, and Poole DC
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- Animals, Blood Chemical Analysis veterinary, Blood Gas Analysis veterinary, Cross-Over Studies, Hemorrhage blood, Hemorrhage prevention & control, Horse Diseases blood, Horses, Isoxazoles therapeutic use, Lung Diseases blood, Lung Diseases prevention & control, Oxygen Consumption physiology, Physical Conditioning, Animal adverse effects, Physical Conditioning, Animal physiology, Pulmonary Wedge Pressure physiology, Sulfonamides therapeutic use, Endothelin-1 antagonists & inhibitors, Endothelin-1 blood, Hemorrhage veterinary, Horse Diseases prevention & control, Lung Diseases veterinary, Pulmonary Wedge Pressure drug effects
- Abstract
Reasons for Performing Study: During high intensity exercise, the very high pulmonary artery pressure (Ppa) experienced by Thoroughbred horses is considered a major factor in the aetiology of exercise-induced pulmonary haemorrhage (EIPH). Recently, endothelin-1 (ET-1), a potent vasoconstrictive hormone, has been found to increase Ppa in horses at rest via binding to its ET-1A receptor subtype. In addition, plasma concentrations of ET-1 are increased in horses during and after high intensity exercise., Hypothesis: If ET-1 increases Ppa during exercise in the horse, administration of a specific ET-1A antagonist would decrease Ppa and therefore EIPH., Methods: Saline (CON) or an ET-1A receptor antagonist, TBC3214 (3 mg/kg bwt i.v.; ANTAG) was administered to horses 1 h prior to maximal incremental exercise on a high-speed treadmill. Gas exchange measurements were made breath-by-breath and blood samples collected during each 1 min stage to determine blood gases, acid-base status and cardiac output. EIPH was determined via bronchoalveolar lavage (BAL) approximately 30 min after exercise., Results: The time to fatigue, gas exchange and cardiovascular responses were not different between groups (P>0.05). Resting and peak Ppa did not differ significantly between treatments. Most importantly, ANTAG did not decrease EIPH., Conclusions: These results do not support a deterministic role for ET-1 in the increased Ppa and therefore EIPH, during maximal exercise in the equine athlete., Potential Relevance: Treatment with an ET-1A receptor antagonist does not appear to be a viable therapeutic intervention in the prevention of EIPH.
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- 2006
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15. Exercise-induced pulmonary haemorrhage during submaximal exercise.
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Epp TS, McDonough P, Padilla DJ, Gentile JM, Edwards KL, Erickson HH, and Poole DC
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- Animals, Blood Gas Analysis veterinary, Bronchoalveolar Lavage Fluid cytology, Erythrocyte Count veterinary, Hemorrhage etiology, Horses, Lung Diseases etiology, Male, Oxygen Consumption, Pulmonary Artery physiology, Pulmonary Circulation physiology, Pulmonary Wedge Pressure physiology, Hemorrhage veterinary, Horse Diseases etiology, Lung Diseases veterinary, Physical Conditioning, Animal adverse effects, Physical Conditioning, Animal physiology
- Abstract
Reasons for Performing Study: Maximally exercising horses achieve mean pulmonary artery pressures (Ppa(mean)) that exceed the minimum threshold (75 mmHg) estimated for pulmonary capillary rupture and exercise-induced pulmonary haemorrhage (EIPH). EIPH is not expected to occur during moderate submaximal exercise (i.e. 40-60% VO2max) since Ppa(mean) remains well below this threshold., Hypothesis: Prolonged submaximal exercise (trotting) would precipitate locomotory respiratory uncoupling and cause EIPH. This would be present as a result of the most negative intrapleural pressures (as estimated by the minimum oesophageal pressure; Poes(min)) occurring simultaneously with the most positive Ppa (Ppa(peak)) to produce estimated maximal pulmonary artery transmural pressures (PATMPmax) that surpass the EIPH threshold., Methods: Five Thoroughbred horses trotted to fatigue (approximately 25 min) at 5 m/sec on a 10% incline. Ventilation (V(E)), Poes, and Ppa were measured at 5 min intervals, and bronchoalveolar lavage (BAL) red blood cells (RBCs) were quantified 45 min post exercise., Results: BAL revealed an increased EIPH (rest: 2.0 +/- 1 x 10(5), exercise: 17 +/- 10 x 10(5) RBCs/ml BALF; P<0.05), despite the highest Ppamean reaching only mean +/- s.e. 55 +/- 3 mmHg, while V(E), tidal volume and Poes(min) approached 70-80% of the values achieved at maximal running speeds (10% incline: 12-13 m/sec) by these same horses. The resulting PATMPmax was well above the level considered causative of EIPH., Conclusions: The finding of significant EIPH during submaximal exercise broadens the spectrum of performance horses susceptible to EIPH and supports studies that suggest that extravascular factors are of primary importance in the aetiology of EIPH., Potential Relevance: Consideration of strategies such as the equine nasal strip for reducing negative extravascular pressures is warranted even for exercise at moderate intensities.
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- 2006
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16. Temporal profile of rat skeletal muscle capillary haemodynamics during recovery from contractions.
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Ferreira LF, Padilla DJ, Musch TI, and Poole DC
- Subjects
- Animals, Blood Flow Velocity, Erythrocytes physiology, Female, Hematocrit, Hemodynamics, Microcirculation, Microscopy, Video, Muscle, Skeletal metabolism, Oxygen metabolism, Rats, Rats, Sprague-Dawley, Regional Blood Flow, Time Factors, Capillaries physiology, Muscle Contraction, Muscle, Skeletal blood supply
- Abstract
In skeletal muscle capillaries, red blood cell (RBC) flux (F(RBC)), velocity (V(RBC)) and haematocrit (Hct(CAP)) are key determinants of microvascular O2 exchange. However, the mechanisms leading to the changes in F(RBC), V(RBC) and Hct(CAP) during muscle contractions and recovery thereafter are not fully understood. To address this issue we used intravital microscopy to investigate the temporal profile of the rat spinotrapezius muscle (n = 5) capillary haemodynamics during recovery from 3 min of twitch muscle contractions (1 Hz, 4-6 V). Specifically, we hypothesized that (1) during early recovery F(RBC) and V(RBC) would decrease rapidly and F(RBC) would display a biphasic response (consistent with a muscle pump effect on capillary haemodynamics), and (2) there would be a dynamic relationship between changes (Delta) in V(RBC) and Hct(CAP). The values at rest (R) and end-recovery (ER) were significantly lower (P < 0.05) than at end-contraction (EC) for F(RBC) (in cells s(-1), R = 30.1 +/- 7.8, EC = 46.2 +/- 7.3 and ER = 26.0 +/- 6.1), V(RBC) (in microm s(-1), R = 368 +/- 83, EC = 497 +/- 62 and ER = 334 +/- 59) and Hct(CAP) (R = 0.193 +/- 0.016, EC = 0.214 +/- 0.023 and ER = 0.185 +/- 0.019). The first data point where a significant decrease in F(RBC), Hct(CAP) and V(RBC) occurred was at 5, 5 and 20 s post-contraction, respectively. The decrease in F(RBC) approximated a monoexponential response (half-time of approximately 26 s). The relationship between DeltaV(RBC) and DeltaHct(CAP) was not significant (P > 0.05). Based on the early decrease in F(RBC) (within 5 s), overall dynamic profile of F(RBC) and the approximately 20 s 'delay' to the decrease in V(RBC) we conclude that the muscle pump does not appear to contribute substantially to the steady-state capillary haemodynamics in the contracting rat spinotrapezius muscle. Moreover, our findings suggest that alterations in V(RBC) do not obligate proportional changes in Hct(CAP) within individual capillaries following muscle contractions.
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- 2006
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17. Effects of altered nitric oxide availability on rat muscle microvascular oxygenation during contractions.
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Ferreira LF, Padilla DJ, Williams J, Hageman KS, Musch TI, and Poole DC
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- Animals, Blood Pressure drug effects, Blood Pressure physiology, Electric Stimulation methods, Female, NG-Nitroarginine Methyl Ester pharmacology, Nitroprusside pharmacology, Oxygen blood, Oxygen Consumption drug effects, Partial Pressure, Rats, Rats, Sprague-Dawley, Vasodilator Agents pharmacology, Muscle Contraction physiology, Muscle, Skeletal physiology, Nitric Oxide physiology, Oxygen Consumption physiology
- Abstract
Aim: To explore the role of nitric oxide (NO) in controlling microvascular O2 pressure (P(O2)mv) at rest and during contractions (1 Hz). We hypothesized that at the onset of contractions sodium nitroprusside (SNP) would raise P(O2)mv and slow the kinetics of P(O2)mv change whereas l-nitro arginine methyl ester (L-NAME) would decrease P(O2)mv and speed its kinetics., Methods: We superfused the spinotrapezius muscle of female Sprague-Dawley rats (n = 7, body mass = 298 +/- 10 g) with SNP (300 microM) and L-NAME (1.5 mm) and measured P(O2)mv (phosphorescence quenching) during contractions., Results: SNP decreased mean arterial pressure (92 +/- 5 mmHg) below that of control (CON, 124 +/- 4 mmHg) and L-NAME (120 +/- 4 mmHg) conditions. SNP did not raise P(O2)mv at rest but it did elevate the P(O2)mv-to-MAP ratio (50% increase, P < 0.05) and slow the kinetics by lengthening the time-delay (TD, 14.0 +/- 5.0 s) and time constant (tau, 24.0 +/- 10.0 s) of the response compared with CON (TD, 8.4 +/- 3.3 s; tau, 16.0 +/- 4.5 s, P < 0.05 vs. SNP). L-NAME decreased P(O2)mv at rest and tended to speed tau (10.1 +/- 3.8 s, P = 0.1), while TD (8.1 +/- 1.0 s) was not significantly different. L-NAME also caused P(O2)mv to fall transiently below steady-state contracting values., Conclusions: These results indicate that NO availability can significantly affect P(O2)mv at rest and during contractions and suggests that P(O2)mv derangements in ageing and chronic disease conditions may potentially result from impairments in NO availability.
- Published
- 2006
- Full Text
- View/download PDF
18. Effects of arterial hypotension on microvascular oxygen exchange in contracting skeletal muscle.
- Author
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Behnke BJ, Padilla DJ, Ferreira LF, Delp MD, Musch TI, and Poole DC
- Subjects
- Animals, Blood Gas Analysis, Blood Pressure, Female, Hypotension blood, Muscle, Skeletal blood supply, Phlebotomy, Rats, Rats, Sprague-Dawley, Regional Blood Flow, Capillary Permeability physiology, Hypotension physiopathology, Muscle Contraction physiology, Muscle, Skeletal physiology, Oxygen metabolism
- Abstract
In healthy animals under normotensive conditions (N), contracting skeletal muscle perfusion is regulated to maintain microvascular O2 pressures (PmvO2) at levels commensurate with O2 demands. Hypovolemic hypotension (H) impairs muscle contractile function; we tested whether this condition would alter the matching of O2 delivery (Qo2) to O2 utilization (Vo2), as determined by PmvO2 at the onset of muscle contractions. PmvO2 in the spinotrapezius muscles of seven female Sprague-Dawley rats (280+/-6 g) was measured every 2 s across the transition from rest to 1-Hz twitch contractions. Measurements were made under N (mean arterial pressure, 97+/-4 mmHg) and H (induced by arterial section; mean arterial pressure, 58+/-3 mmHg, P<0.05) conditions; PmvO2 profiles were modeled using a multicomponent exponential fitted with independent time delays. Hypotension reduced muscle blood flow at rest (24+/-8 vs. 6+/-1 ml-1.min-1.100 g-1 for N and H, respectively; P<0.05) and during contractions (74+/-20 vs. 22+/-4 ml-1.min-1.100 g-1 for N and H, respectively; P<0.05). H significantly decreased resting PmvO2 and steady-state contracting PmvO2(19.4+/-2.4 vs. 8.7+/-1.6 Torr for N and H, respectively, P<0.05). At the onset of contractions, H reduced the time delay (11.8+/-1.7 vs. 5.9+/-0.9 s for N and H, respectively, P<0.05) before the fall in PmvO2 and accelerated the rate of PmvO2 decrease (time constant, 12.6+/-1.4 vs. 7.3+/-0.9 s for N and H, respectively, P<0.05). Muscle Vo2 was reduced by 71% at rest and 64% with contractions in H vs. N, and O2 extraction during H averaged 78% at rest and 94% during contractions vs. 51 and 78% in N. These results demonstrate that H constrains the increase of skeletal muscle Qo2 relative to that of Vo2 at the onset of contractions, leading to a decreased PmvO2. According to Fick's law, this scenario will decrease blood-myocyte O2 flux, thereby slowing Vo2 kinetics and exacerbating the O2 deficit generated at exercise onset.
- Published
- 2006
- Full Text
- View/download PDF
19. Effects of eccentric exercise on microcirculation and microvascular oxygen pressures in rat spinotrapezius muscle.
- Author
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Kano Y, Padilla DJ, Behnke BJ, Hageman KS, Musch TI, and Poole DC
- Subjects
- Animals, Blood Flow Velocity, Capillaries, Erythrocyte Volume, Female, Microcirculation, Partial Pressure, Rats, Rats, Sprague-Dawley, Motor Activity physiology, Muscle, Skeletal blood supply, Oxygen blood
- Abstract
A single bout of eccentric exercise results in muscle damage, but it is not known whether this is correlated with microcirculatory dysfunction. We tested the following hypotheses in the spinotrapezius muscle of rats either 1 (DH-1; n = 6) or 3 (DH-3; n = 6) days after a downhill run to exhaustion (90-120 min; -14 degrees grade): 1) in resting muscle, capillary hemodynamics would be impaired, and 2) at the onset of subsequent acute concentric contractions, the decrease of microvascular O(2) pressure (Pmv(o(2))), which reflects the dynamic balance between O(2) delivery and O(2) utilization, would be accelerated compared with control (Con, n = 6) rats. In contrast to Con muscles, intravital microscopy observations revealed the presence of sarcomere disruptions in DH-1 and DH-3 and increased capillary diameter in DH-3 (Con: 5.2 +/- 0.1; DH-1: 5.1 +/- 0.1; DH-3: 5.6 +/- 0.1 mum; both P < 0.05 vs. DH-3). At rest, there was a significant reduction in the percentage of capillaries that sustained continuous red blood cell (RBC) flux in both DH running groups (Con: 90.0 +/- 2.1; DH-1: 66.4 +/- 5.2; DH-3: 72.9 +/- 4.1%, both P < 0.05 vs. Con). Capillary tube hematocrit was elevated in DH-1 but reduced in DH-3 (Con: 22 +/- 2; DH-1: 28 +/- 1; DH-3: 16 +/- 1%; all P < 0.05). Although capillary RBC flux did not differ between groups (P > 0.05), RBC velocity was lower in DH-1 compared with Con (Con: 324 +/- 43; DH-1: 212 +/- 30; DH-3: 266 +/- 45 mum/s; P < 0.05 DH-1 vs. Con). Baseline Pmv(O(2)) before contractions was not different between groups (P > 0.05), but the time constant of the exponential fall to contracting Pmv(O(2)) values was accelerated in the DH running groups (Con: 14.7 +/- 1.4; DH-1: 8.9 +/- 1.4; DH-3: 8.7 +/- 1.4 s, both P < 0.05 vs. Con). These findings are consistent with the presence of substantial microvascular dysfunction after downhill eccentric running, which slows the exercise hyperemic response at the onset of contractions and reduces the Pmv(O(2)) available to drive blood-muscle O(2) delivery.
- Published
- 2005
- Full Text
- View/download PDF
20. Dynamics of muscle microcirculatory oxygen exchange.
- Author
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Poole DC, Behnke BJ, and Padilla DJ
- Subjects
- Cardiovascular Diseases metabolism, Cardiovascular Diseases physiopathology, Erythrocytes metabolism, Exercise physiology, Humans, Kinetics, Microcirculation metabolism, Muscle Contraction physiology, Oxygen Consumption physiology, Partial Pressure, Muscle, Skeletal blood supply, Muscle, Skeletal metabolism, Oxygen metabolism
- Abstract
Purpose: Beyond the initial cardiodynamic "Phase I," pulmonary oxygen uptake (VO(2)) kinetics are dictated largely by, and resemble closely, the VO(2) of the exercising muscles (VO(2)m). Within those muscles, the microcirculation is responsible for affecting almost all blood-myocyte O(2) transfer, and thus, observations at this site may provide key insights into muscle oxidative function in health and dysfunction in disease., Methods: Recently, a novel combination of microscopy and phosphorescence quenching techniques has been utilized to understand the dynamics of microvascular O(2) delivery (VO(2)m) and muscle O(2) utilization (VO(2)m) at the onset of muscle contractions., Results: These experiments have addressed longstanding questions regarding the site of control of VO(2)m kinetics and provide a first look at capillary hemodynamics at exercise onset in healthy muscle and their derangements resulting from chronic diseases such as heart failure and diabetes., Conclusion: This paper will review these novel findings within our current understanding of microcirculatory control and blood-myocyte O(2) transfer.
- Published
- 2005
- Full Text
- View/download PDF
21. Control of microvascular oxygen pressures in rat muscles comprised of different fibre types.
- Author
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McDonough P, Behnke BJ, Padilla DJ, Musch TI, and Poole DC
- Subjects
- Animals, Blood Flow Velocity physiology, Female, Rats, Rats, Sprague-Dawley, Microcirculation physiology, Muscle Contraction physiology, Muscle Fibers, Skeletal physiology, Muscle, Skeletal blood supply, Muscle, Skeletal physiology, Oxygen blood, Oxygen Consumption physiology, Physical Exertion physiology
- Abstract
In response to an elevated metabolic rate ((.-)V(O(2)), increased microvascular blood-muscle O(2) flux is the product of both augmented O(2) delivery ((.-)Q(O(2)), and fractional O(2) extraction. Whole body and exercising limb measurements demonstrate that (.-)Q(O(2) and fractional O(2) extraction increase as linear and hyperbolic functions, respectively, of (.-)V(O(2). Given the presence of disparate vascular control mechanisms among different muscle fibre types, we tested the hypothesis that, in response to muscle contractions, (.-)Q(O(2) would be lower and fractional O(2) extraction (as assessed via microvascular O(2) pressure, P(mvO(2))) higher in fast- versus slow-twitch muscles. Radiolabelled microsphere and phosphorescence quenching techniques were used to measure (.-)Q(O(2) and P(mvO(2)), respectively at rest and across the transition to 1 Hz twitch contractions at low (Lo, 2.5 V) and high intensities (Hi, 4.5 V) in rat (n = 20) soleus (Sol, slow-twitch, type I), mixed gastrocnemius (MG, fast-twitch, type IIa) and white gastrocnemius (WG, fast-twitch, type IIb) muscle. At rest and for Lo and Hi (steady-state values) transitions, P(mvO(2)) was lower (all P < 0.05) in MG (mmHg: rest, 22.5 +/- 1.0; Lo, 15.3 +/- 1.3; Hi, 10.2 +/- 1.6) and WG (mmHg: rest, 19.0 +/- 1.3; Lo, 12.2 +/- 1.1; Hi, 9.9 +/- 1.1) than in Sol (rest, 33.1 +/- 3.2 mmHg; Lo, 19.0 +/- 2.3 mmHg; Hi, 18.7 +/- 1.8 mmHg), despite lower (.-)V(O(2) and (.-)Q(O(2) in MG and WG under each set of conditions. These data suggest that during submaximal metabolic rates, the relationship between (.-)Q(O(2) and O(2) extraction is dependent on fibre type (at least in the muscles studied herein), such that muscles comprised of fast-twitch fibres display a greater fractional O(2) extraction (i.e. lower P(mvO(2))) than their slow-twitch counterparts. These results also indicate that the greater sustained P(mvO(2)) in Sol may be important for ensuring high blood-myocyte O(2) flux and therefore a greater oxidative contribution to energetic requirements.
- Published
- 2005
- Full Text
- View/download PDF
22. Ventilatory dynamics and control of blood gases after maximal exercise in the Thoroughbred horse.
- Author
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Padilla DJ, McDonough P, Kindig CA, Erickson HH, and Poole DC
- Subjects
- Animals, Blood Gas Analysis veterinary, Exercise Test veterinary, Motor Activity, Oxygen Consumption, Physical Conditioning, Animal, Rest, Horses blood, Horses physiology, Oxygen blood, Respiratory Mechanics
- Abstract
Despite enormous rates of minute ventilation (Ve) in the galloping Thoroughbred (TB) horse, the energetic demands of exercise conspire to raise arterial Pco(2) (i.e., induce hypercapnia). If locomotory-respiratory coupling (LRC) is an obligatory facilitator of high Ve in the horse such as those found during galloping (Bramble and Carrier. Science 219: 251-256, 1983), Ve should drop precipitously when LRC ceases at the galloptrot transition, thus exacerbating the hypercapnia. TB horses (n = 5) were run to volitional fatigue on a motor-driven treadmill (1 m/s increments; 14-15 m/s) to study the dynamic control of breath-by-breath Ve, O(2) uptake, and CO(2) output at the transition from maximal exercise to active recovery (i.e., trotting at 3 m/s for 800 m). At the transition from the gallop to the trot, Ve did not drop instantaneously. Rather, Ve remained at the peak exercising levels (1,391 +/- 88 l/min) for approximately 13 s via the combination of an increased tidal volume (12.6 +/- 1.2 liters at gallop; 13.9 +/- 1.6 liters over 13 s of trotting recovery; P < 0.05) and a reduced breathing frequency [113.8 +/- 5.2 breaths/min (at gallop); 97.7 +/- 5.9 breaths/min over 13 s of trotting recovery (P < 0.05)]. Subsequently, Ve declined in a biphasic fashion with a slower mean response time (85.4 +/- 9.0 s) than that of the monoexponential decline of CO(2) output (39.9 +/- 4.7 s; P < 0.05), which rapidly reversed the postexercise arterial hypercapnia (arterial Pco(2) at gallop: 52.8 +/- 3.2 Torr; at 2 min of recovery: 25.0 +/- 1.4 Torr; P < 0.05). We conclude that LRC is not a prerequisite for achievement of Ve commensurate with maximal exercise or the pronounced hyperventilation during recovery.
- Published
- 2004
- Full Text
- View/download PDF
23. Oxygen exchange profile in rat muscles of contrasting fibre types.
- Author
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Behnke BJ, McDonough P, Padilla DJ, Musch TI, and Poole DC
- Subjects
- Animals, Capillaries anatomy & histology, Electric Stimulation, Female, Homeostasis, Microcirculation, Muscle Contraction, Muscle, Skeletal anatomy & histology, Muscle, Skeletal blood supply, Oxygen blood, Partial Pressure, Rats, Rats, Sprague-Dawley, Muscle Fibers, Fast-Twitch metabolism, Muscle Fibers, Slow-Twitch metabolism, Muscle, Skeletal metabolism, Oxygen Consumption
- Abstract
To determine whether fibre type affects the O2 exchange characteristics of skeletal muscle at the microcirculatory level we tested the hypothesis that, following the onset of contractions, muscle comprising predominately type I fibres (soleus, Sol, 86 % type I) would, based on demonstrated blood flow responses, exhibit a blunted microvascular PO2 (PO2,m, which is determined by the O2 delivery (QO2) to O2 uptake (VO2) ratio) profile (assessed via phosphorescence quenching) compared to muscle of primarily type II fibres (peroneal, Per, 84 % type II). PO2,m was measured at rest, and following the rest-contractions (twitch, 1 Hz, 2-4 V for 120 s) transition in Sol (n = 6) and Per (n = 6) muscles of Sprague-Dawley rats. Both muscles exhibited a delay followed by a mono-exponential decrease in PO2,m to the steady state. However, compared with Sol, Per demonstrated (1) a larger change in baseline minus steady state contracting PO2,m (DeltaPO2,m) (Per, 13.4 +/- 1.7 mmHg; Sol, 8.6 +/- 0.9 mmHg, P < 0.05); (2) a faster mean response time (i.e. time delay (TD) plus time constant (tau); Per, 23.8 +/- 1.5 s; Sol, 39.6 +/- 4.3 s, P < 0.05); and therefore (3) a greater rate of PO2,m decline (DeltaPO2,m/tau; Per, 0.92 +/- 0.08 mmHg s-1; Sol, 0.42 +/- 0.05 mmHg s-1, P < 0.05). These data demonstrate an increased microvascular pressure head of O2 at any given point after the initial time delay for Sol versus Per following the onset of contractions that is probably due to faster QO2 dynamics relative to those of VO2.
- Published
- 2003
- Full Text
- View/download PDF
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