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OBJECTIVES:. To develop and validate a prediction model for 1-year mortality in patients with a hematologic malignancy acutely admitted to the ICU. DESIGN:. A retrospective cohort study. SETTING:. Five university hospitals in the Netherlands between 2002 and 2015. PATIENTS:. A total of 1097 consecutive patients with a hematologic malignancy were acutely admitted to the ICU for at least 24 h. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. We created a 13-variable model from 22 potential predictors. Key predictors included active disease, age, previous hematopoietic stem cell transplantation, mechanical ventilation, lowest platelet count, acute kidney injury, maximum heart rate, and type of malignancy. A bootstrap procedure reduced overfitting and improved the model’s generalizability. This involved estimating the optimism in the initial model and shrinking the regression coefficients accordingly in the final model. We assessed performance using internal–external cross-validation by center and compared it with the Acute Physiology and Chronic Health Evaluation II model. Additionally, we evaluated clinical usefulness through decision curve analysis. The overall 1-year mortality rate observed in the study was 62% (95% CI, 59–65). Our 13-variable prediction model demonstrated acceptable calibration and discrimination at internal–external validation across centers (C-statistic 0.70; 95% CI, 0.63–0.77), outperforming the Acute Physiology and Chronic Health Evaluation II model (C-statistic 0.61; 95% CI, 0.57–0.65). Decision curve analysis indicated overall net benefit within a clinically relevant threshold probability range of 60–100% predicted 1-year mortality. CONCLUSIONS:. Our newly developed 13-variable prediction model predicts 1-year mortality in hematologic malignancy patients admitted to the ICU more accurately than the Acute Physiology and Chronic Health Evaluation II model. This model may aid in shared decision-making regarding the continuation of ICU care and end-of-life considerations.

Ethanol infusion has been used for the treatment of ventricular arrhythmia. We describe a case of ethanol infusion through the coronary sinus venous network to treat refractory epicardial premature ventricular complexes. The premature ventricular complexes were initially successfully suppressed but recurred after resolution of the myocardial edema. (Level of Difficulty: Intermediate.)

Introduction/Objectives We examined an initial step towards co-generation of clinic notes by inviting patients to complete a pre-visit questionnaire that could be inserted into clinic notes by providers and describe the experience in a safety-net and non-safety-net clinic. Methods We sent an electronic pre-visit questionnaire on visit goals and interim history to patients at a safety-net clinic and a non-safety-net clinic before clinic visits. We compared questionnaire utilization between clinics during a one-year period and performed a chart review of a sample of patients to examine demographics, content and usage of patient responses to the questionnaire. Results While use was low in both clinics, it was lower in the safety-net clinic (3%) compared to the non-safety-net clinic (10%). We reviewed a sample of respondents and found they were more likely to be White compared to the overall clinic populations ( p

Objectives:. Iatrogenic cerebral arterial gas embolism occurs when gas enters the cerebral arterial circulation during a medical procedure and is considered a severe complication. Seizures have been described in these patients, but information on clinical characteristics, treatment, and outcome is lacking in current literature. The aim of the study was to explore seizures in patients with iatrogenic cerebral arterial gas embolism and to evaluate management strategies. Design:. Retrospective single-center observational study. Setting:. The only university hospital in the Netherlands with a hyperbaric oxygen therapy facility. Patients:. All patients presenting at or referred to our center with iatrogenic cerebral arterial gas embolism between May 2016 and December 2020. Interventions:. Not applicable. Measurements and Main Results:. Fifteen patients with iatrogenic cerebral arterial gas embolism were identified, of whom 11 (73%) developed seizures. Five patients developed their first seizure prior to hyperbaric oxygen therapy, three during hyperbaric oxygen therapy, and three after hyperbaric oxygen therapy. Of the 11 patients with seizures, all but one were treated with anti-epileptic drugs. With a median follow-up time of 5 months (range, 1–54 mo), five patients showed complete neurologic recovery, five had minor neurologic deficit, two had moderate to severe neurologic deficit, and three had died. Four patients still used anti-epileptic drugs at follow-up. No patients had recurrent seizures after hospital discharge. Conclusions:. `Seizures are a common symptom in iatrogenic cerebral arterial gas embolism. They are often treated with anti-epileptic drugs and do not seem to lead to chronic epilepsy.

Purpose: Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL). Methods and materials: The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes. Results: Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count

Abstract. The 2018 Edition of the Declaration of Istanbul on Organ Trafficking and Transplant Tourism (DoI) provides an updated set of principles and definitions to guide policymakers and health professionals working in organ donation and transplantation. A draft of the new edition was circulated to the public and transplant professionals through an online consultation process, which also sought feedback on a draft explanatory article that explained the principles and discussed some of their practical implications. Both drafts were revised in response to feedback from participants in the consultation. We present here the discussion article, which is intended to assist stakeholders in applying the principles of the DoI by providing more detailed information about the meaning and potential implications of implementing the DoI in various contexts.

Background: Silent cerebral events (SCE) have been identified on magnetic resonance imaging (MRI) in asymptomatic patients after atrial fibrillation (AF) ablation. Procedural determinants influencing the risk for SCE still remain unclear. Objective: Comparing the risk for SCE depending on exchanges of catheters (ExCath) over a single transseptal sheath. Methods: 88 Patients undergoing pulmonary vein isolation (PVI) only ablation using either single-tip or balloon-based technique underwent pre- and post-ablation cerebral MRI. Ablations were either performed with double transseptal access and without exchanging catheters over the transseptal sheaths (group 1: no ExCath) or after a single transseptal access and exchanges of therapeutic and diagnostic catheters (group 2: ExCath). Differences in regard to SCE rates were analyzed. Multivariate analysis was performed to identify factors related to the risk for SCE. Results: Included patients underwent PVI using single tip irrigated radiofrequency in 41, endoscopic laser balloon in 27 and cryoballoon in 20 cases. Overall SCE were identified in 23 (26%) patients. In group 1 (no ExCath; N=46) 6 patients (13%) and in group 2 (N=42) 17 patients (40%) had documented SCE (p=0.007). The applied ablation technology did not affect sCe rate. In multivariate analysis age (OR 1.1, p=0.03) and catheter exchanges over a single transseptal sheath (OR 12.1, p=0.007) were the only independent predictors of a higher risk for SCE. Conclusions: Exchanging catheters over a single transseptal access to perform left atrial ablation is associated with a significantly higher incidence of SCE compared to an ablation technique using different transseptal accesses for therapeutic and diagnostic catheters.

Supplementary oxygen is commonly administered in current medical practice. Recently it has been suggested that hyperoxia causes acute oxidative stress and produces prompt and substantial changes in coronary resistance in patients with ischemic heart disease. In this report, we examined whether the effects of hyperoxia on coronary blood velocity (CBV) would be associated with a reduction in myocardial function. We were also interested in determining if the postulated changes in left ventricular (LV) function seen with tissue Doppler imaging (TDI) could be reversed with intravenous vitamin C, a potent, acute anti-oxidant. LV function was determined in eight healthy subjects with transthoracic echocardiography and TDI before and after hyperoxia and with and without infusing vitamin C. Hyperoxia compared with room air promptly reduced CBV by 28 ± 3% (from 23.50 ± 2.31 cm/s down to 17.00 ± 1.79 cm/s) and increased relative coronary resistance by 34 ± 5% (from 5.63 ± 0.88 up to 7.32 ± 0.94). Meanwhile, LV myocardial systolic velocity decreased by 11 ± 6% (TDI). These effects on flow and function were eliminated by the infusion of vitamin C, suggesting that these changes are mediated by vitamin C-quenchable substances acting on the coronary microcirculation. [ABSTRACT FROM AUTHOR]

Younger women rely on altering cardiac output ( Q ̇ $\dot{Q}$ ) to regulate blood pressure (BP). In contrast, older women rely more on altering vascular tone. However, evidence suggests that the ability to alter systemic vascular conductance (SVC) is diminished in older women. In the present study, cardioselective β-blockade was utilized to diminish the relative contribution of Q ̇ $\dot{Q}$ to BP regulation and thereby evaluate age-related vascular limitations in women at rest and during large muscle dynamic exercise. Younger (n = 13, mean age 26.0 years) and older (n = 14, mean age 61.8 years) healthy women performed submaximal bouts of semi-recumbent cycling exercise at varying intensities while receiving an intravenous infusion of esmolol, a β 1 -antagonist, or saline control in a repeated-measures crossover design. Q ̇ $\dot{Q}$ was attenuated during esmolol infusion, with greater reductions during exercise (moderate, -1.0 (95% CI, -1.6 to -0.5) L/min, P < 0.001; heavy, -2.0 (95% CI, -2.6 to -1.5) L/min, P < 0.001) than seated rest (-0.5 (95% CI, -1.1 to 0.0) L/min, P = 0.048), and this reduction was not significantly different between age groups (P = 0.122). Older women exhibited a greater attenuation in mean arterial pressure (MAP) during esmolol (-7 (95% CI, -9 to -4) mmHg, P < 0.001) relative to younger women (-2 (95% CI, -5 to 0) mmHg, P = 0.071). These changes coincided with a greater reduction of SVC in the younger women during esmolol (-15 (95% CI, -20 to -10) mL/min/mmHg, P < 0.001) compared to older women (-3 (95% CI, -9 to 2) mL/min/mmHg, P = 0.242). Together, these findings provide evidence that older, postmenopausal women have a diminished ability to adjust SVC in order to regulate MAP., (© 2024 The Author(s). Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.)

Global warming poses significant challenges to the fertility of tropical dairy cattle. One promising approach to mitigate heat stress effects on reproductive function and reduce the carbon footprint is the use of integrated livestock-forest (ILF) systems. The aim of this study was to investigate the effects of two different systems, namely Full Sun (FS) and ILF, on maternal hyperthermia and oocyte quality of Holstein and Girolando heifers during the tropical summer season. The temperature-humidity index (THI) data revealed intense heat stress during the experiment. Both the system (P<0.01) and the breed (P<0.01) factors had a significant impact on vaginal temperature, being hyperthermia more pronounced in the FS system and in the Holstein breed. Over the five time points collected at a 33-day interval, we observed distinct patterns for ILF (P=0.65) and FS (P<0.001) systems, suggesting an adaptive response in animals kept in FS systems. Furthermore, oocyte quality assessment revealed an effect of the system for oocyte diameter (P<0.001) and levels of IGFBP2 (P<0.001), and caspase 3 levels showed a decrease in ILF compared to FS for both Holstein (P<0.001) and Girolando (P<0.001) breeds. Collectively, these parameters indicate that oocyte quality during the summer months was superior in animals maintained in the ILF system. In conclusion, the ILF system demonstrated promising results in attenuating maternal hyperthermia and mitigating its effects on oocyte quality. Additionally, our observations suggest that animals in the FS system may exhibit an adaptive response to heat stress., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD., Objective: We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise., Methods: Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BR nitrate ) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BR placebo ) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured., Results: Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BR placebo and BR nitrate , the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BR nitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BR placebo and BR nitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BR nitrate ( p  = 0.06; Cohen's d  = 0.56)., Conclusion: Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia. Clinical trial registration: https://clinicaltrials.gov/, identifier NCT02553733., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kim, Gao, Luck, Brandt, Miller, Kim-Shapiro, Basu, Leuenberger, Gardner, Muller and Proctor.)

Background: Individual functional modifications shape the ability of wildlife populations to cope with anthropogenic environmental changes. But instead of adaptive response, human-altered environments can generate a succession of deleterious functional changes leading to the extinction of the population. To study how persistent anthropogenic changes impacted local species' population status, we characterised population structure, genetic diversity and individual response of gene expression in the tree frog Hyla orientalis along a gradient of radioactive contamination around the Chernobyl nuclear power plant., Results: We detected lower effective population size in populations most exposed to ionizing radiation in the Chernobyl Exclusion Zone that is not compensated by migrations from surrounding areas. We also highlighted a decreased body condition of frogs living in the most contaminated area, a distinctive transcriptomics signature and stop-gained mutations in genes involved in energy metabolism. While the association with dose will remain correlational until further experiments, a body of evidence suggests the direct or indirect involvement of radiation exposure in these changes., Conclusions: Despite ongoing migration and lower total dose rates absorbed than at the time of the accident, our results demonstrate that Hyla orientalis specimens living in the Chernobyl Exclusion Zone are still undergoing deleterious changes, emphasizing the long-term impacts of the nuclear disaster., (© 2023. The Author(s).)

Exercise tolerance appears to benefit most from dietary nitrate (NO 3 - ) supplementation when muscle oxygen (O 2 ) availability is low. Using a double-blind, randomized cross-over design, we tested the hypothesis that acute NO 3 - supplementation would improve blood flow restricted exercise duration in post-menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57-76 yr) performed rhythmic isometric handgrip contractions (10% MVC, 30 per min) during progressive forearm blood flow restriction (upper arm cuff gradually inflated 20 mmHg each min) on three study visits, with 7-10 days between visits. Approximately one week following the first (familiarization) visit, participants consumed 140 ml of NO 3 - concentrated (9.7 mmol, 0.6 gm NO 3 - ) or NO 3 - depleted beetroot juice (placebo) on separate days (≥7 days apart), with handgrip exercise beginning 100 min post-consumption. Handgrip force recordings were analyzed to determine if NO 3 - supplementation enhanced force development as blood flow restriction progressed. Nitrate supplementation increased plasma NO 3 - (16.2-fold) and NO 2 - (4.2-fold) and time to volitional fatigue (61.8 ± 56.5 s longer duration vs. placebo visit; p = 0.03). Nitrate supplementation increased the rate of force development as forearm muscle ischemia progressed (p = 0.023 between 50 and 75% of time to fatigue) with non-significant effects thereafter (p = 0.052). No effects of nitrate supplementation were observed for mean duration of contraction or relaxation rates (all p > 0.150). These results suggest that acute NO 3 - supplementation prolongs time-to-fatigue and speeds grip force development during progressive forearm muscle ischemia in postmenopausal women., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study is to analyze and compare the performance and strategies used by control subjects and patients with unilateral brain damage on phonemic and semantic Verbal Fluency tasks., Methods: The sample consisted of 104 participants divided into four groups (26 with left hemisphere damage and aphasia- LHDa, 28 with left hemisphere damage and no aphasia- LHDna, 25 with right hemisphere damage- RHD and 25 neurologically healthy control subjects). All participants were administered the phonemic ("M" letter-based) and semantic (animals) verbal fluency tasks from the Montreal-Toulouse Language Assessment Battery (MTL-BR)., Results: Patients in the LHDa group showed the worst performance (fewer words produced, fewer clusters and switches) in both types of fluency task. RHD group showed fewer switching productions when compared with controls and LHDna had fewer words productions than controls in the first 30 seconds block., Conclusion: Our findings suggest that the LHDa group obtained lower scores in most measures of SVF and PVF when compared to the other groups.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome that is characterised by a high prevalence of diffuse gastric cancer and lobular breast cancer. It is largely caused by inactivating germline mutations in the tumour suppressor gene CDH1, although pathogenic variants in CTNNA1 occur in a minority of families with HDGC. In this Policy Review, we present updated clinical practice guidelines for HDGC from the International Gastric Cancer Linkage Consortium (IGCLC), which recognise the emerging evidence of variability in gastric cancer risk between families with HDGC, the growing capability of endoscopic and histological surveillance in HDGC, and increased experience of managing long-term sequelae of total gastrectomy in young patients. To redress the balance between the accessibility, cost, and acceptance of genetic testing and the increased identification of pathogenic variant carriers, the HDGC genetic testing criteria have been relaxed, mainly through less restrictive age limits. Prophylactic total gastrectomy remains the recommended option for gastric cancer risk management in pathogenic CDH1 variant carriers. However, there is increasing confidence from the IGCLC that endoscopic surveillance in expert centres can be safely offered to patients who wish to postpone surgery, or to those whose risk of developing gastric cancer is not well defined., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: Patients diagnosed with peripheral artery disease are difficult to recruit into clinical trials. However, there is currently no high-quality, patient-centered information explaining why peripheral artery disease patients choose to participate or not participate in clinical research studies., Methods: The current study was a prospective community engagement initiative that specifically asked patients with and without peripheral artery disease: (1) what motivates them to participate in clinical research studies, (2) their willingness to participate in different research procedures, (3) the barriers to participation, (4) preferences about study design, and (5) demographic and disease-related factors influencing participation. Data were gathered through focus groups ( n  = 19, participants aged 55-79 years) and mailed questionnaires ( n  = 438, respondents aged 18-85 years)., Results: More than half of the respondents stated that they would be willing to participate in a study during evening or weekend time slots. Peripheral artery disease patients ( n  = 45) were more willing than those without peripheral artery disease ( n  = 360) to participate in drug infusion studies (48% versus 18%, p  < 0.001) and trials of investigational drugs (44% versus 21%, p  < 0.001). Motivating factors and barriers to participation were largely consistent with previous studies., Conclusion: Adults in our geographic region are interested in participating in clinical research studies related to their health; they would like their doctor to tell them what studies they qualify for and they prefer to receive a one-page advertisement that has color pictures of the research procedures. Peripheral artery disease patients are more willing than those without peripheral artery disease to participate in drug infusion studies, trials of investigational drugs, microneurography, and spinal/epidural infusions., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

In 1930, the life expectancy of patients with Down syndrome was about 10 years; today, their life expectancy is more than 60 years. With aging, there is an increased need for anesthesia and surgery. There is, however, no published information regarding the anesthetic management of older adults with Down syndrome. In this report, we described the anesthetic management of a 50-year-old woman with Down syndrome undergoing major cervical spine surgery. Components of the anesthetic that we thought would be difficult such as intravenous line placement and endotracheal intubation were accomplished without difficulty. Despite our best efforts, our patient nevertheless experienced both emergence delirium and postoperative vomiting. We advocate that physicians, advanced practice providers, and registered nurses be aware of the unique perianesthesia needs of older patients with Down syndrome., (Copyright © 2019 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.)

Smoking is a risk factor for cardiovascular diseases. Prior reports showed a transient increase in blood pressure (BP) following a spontaneous burst of muscle sympathetic nerve activity (MSNA). We hypothesized that this pressor response would be accentuated in smokers. Using signal-averaging techniques, we examined the BP (Finometer) response to MSNA in 18 otherwise healthy smokers and 42 healthy nonsmokers during resting conditions. The sensitivities of baroreflex control of MSNA and heart rate were also assessed. The mean resting MSNA, heart rate, and mean arterial pressure (MAP) were higher in smokers than nonsmokers. The MAP increase following a burst of MSNA was significantly greater in smokers than nonsmokers (Δ3.4 ± 0.3 vs. Δ1.6 ± 0.1 mmHg, P < 0.001). The baroreflex sensitivity (BRS) of burst incidence, burst area, or total activity was not different between the two groups. However, cardiac BRS was lower in smokers than nonsmokers (14.6 ± 1.7 vs. 24.6 ± 1.5 ms/mmHg, P < 0.001). Moreover, the MAP increase following a burst was negatively correlated with the cardiac BRS. These observations suggest that habitual smoking in otherwise healthy individuals raises the MAP increase following spontaneous MSNA and that the attenuated cardiac BRS in the smokers was a contributing factor. We speculate that the accentuated pressor increase in response to spontaneous MSNA may contribute to the elevated resting BP in the smokers.

Purpose: Consumption of nitrate-rich beetroot juice can lower blood pressure in peripheral as well as central arteries and may exert additional hemodynamic benefits (e.g. reduced aortic wave reflections). The specific influence of nitrate supplementation on arterial pressures and aortic wave properties in postmenopausal women, a group that experiences accelerated increases in these variables with age, is unknown. Accordingly, the primary aim of this study was to determine the effect of consuming nitrate-rich beetroot juice on resting brachial and aortic blood pressures (BP) and pulse wave characteristics in a group of healthy postmenopausal women, in comparison to a true (nitrate-free beetroot juice) placebo., Methods: Brachial (oscillometric cuff) and radial (SphygmoCor) pressures and derived-aortic waveforms were measured during supine rest in thirteen healthy postmenopausal women (63 ± 1 yr) before and 100 min after consumption of 140 ml of either nitrate-rich (9.7 mmol, 0.6 gm NO 3 - ) or nitrate-depleted beetroot juice on randomized visits approximately 10 days apart (cross-over design). Ten young premenopausal women (22 ± 1 yr) served as a reference (non-supplemented) cohort., Results: Brachial and derived-aortic variables showed the expected age-associated differences in these women (all p < 0.05). In post-menopausal women, nitrate supplementation reduced (p < 0.05 vs. placebo visit) brachial systolic BP (BR nitrate -4.9 ± 2.1 mmHg vs BR placebo +1.1 ± 1.8 mmHg), brachial mean BP (BR nitrate -4.1 ± 1.7 mmHg vs BR placebo +0.9 ± 1.3 mmHg), aortic systolic BP (BR nitrate -6.3 ± 2.0 mmHg vs BR placebo +0.5 ± 1.7 mmHg) and aortic mean BP (BR nitrate -4.1 ± 1.7 mmHg vs BR placebo +0.9 ± 1.3 mmHg), and increased pulse pressure amplification (BR nitrate +4.6 ± 2.0% vs BR placebo +0.7 ± 2.5%, p = 0.04), but did not alter aortic pulse wave velocity or any other derived-aortic variables (e.g., augmentation pressure or index)., Conclusions: Dietary nitrate supplementation favorably modifies aortic systolic and mean blood pressure under resting conditions in healthy postmenopausal women. Acute supplementation of nitrate does not, however, appear to restore indices of aortic stiffness in this group. Future work should evaluate chronic, long-term effects of this non-pharmacological supplement., (Copyright © 2019. Published by Elsevier Inc.)

Emerging evidence suggests that sympathetic vasoconstriction is lower in young women. We hypothesized that increases in muscle sympathetic nerve activity (MSNA) during acute physiological stressors induce less vasoconstriction in young women compared to young men. Healthy young men (n = 10, 27 ± 1 years), young women (n = 12, 25 ± 1 years), and older women (n = 10, 63 ± 6 years) performed the cold pressor test (hand in ice for 2 min) and continuous hypoxia (10% O 2 , 90% N 2 ) for 5 min. MSNA, femoral blood flow velocity, heart rate, and blood pressure were acquired continuously. Femoral artery diameter was obtained every minute and used to calculate femoral blood flow, and femoral vascular resistance and conductance. MSNA responses to cold pressor test (P = 0.345) and hypoxia (P = 0.969) were not different between groups. Young women had greater femoral blood flow (P = 0.002) and vascular conductance (P = 0.041) responses to cold pressor test compared with young men. The femoral blood flow response to hypoxia was not different between the two sexes but the increase in femoral flow was attenuated in older women compared with younger women (P = 0.036). These data show that young women had paradoxical vasodilation to cold pressor test. The mechanisms responsible for the attenuated sympathetic vasoconstriction or for enhanced vasodilation in young women during the CPT require further investigation., (© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

Peripheral arterial disease (PAD) is associated with augmented blood pressure (BP) and impaired coronary blood flow responses to exercise, which may increase cardiovascular risk. We investigated the effects of leg revascularization on the BP and coronary blood flow responses to exercise in PAD. Seventeen PAD patients (11 men, 66 ± 2 yr) performed single-leg plantar flexion exercise 24 h before and 1 mo following leg revascularization. BP and heart rate (HR) were measured continuously, and rate pressure product (systolic BP × HR) was calculated as an index of myocardial oxygen demand. Coronary blood velocity was obtained by transthoracic Doppler echocardiography in 8/17 subjects. The mean BP response to plantar flexion exercise was attenuated by leg revascularization (pre-revascularization: 15 ± 4 vs. post-revascularization: 7 ± 3 mmHg, P = 0.025). The HR response to plantar flexion was also attenuated following leg revascularization (pre-revascularization: 9 ± 1 vs. post-revascularization: 6 ± 1 beats/min, P = 0.006). The change in coronary blood velocity with exercise was greater at the post-revascularization visit: 4 ± 1 vs. pre-revascularization: -1 ± 2 cm/s ( P = 0.038), even though the change in rate pressure product was not greater following revascularization in these subjects (pre-revascularization: 2,796 ± 871 vs. post-revascularization: 1,766 ± 378 mmHg·beats/min, P = 0.082). These data suggest that leg revascularization alters reflex control of BP, HR, and coronary blood flow in response to exercise in patients with PAD. NEW & NOTEWORTHY We found that peripheral revascularization procedures lowered exercise blood pressure and improved coronary blood flow in patients with peripheral arterial disease.

Beta-adrenoreceptor antagonists (β blockers) reduce systemic O 2 delivery and blood pressure (BP) during exercise, but the subsequent effects on O 2 extraction within the active limb muscles are unknown. In this study, we examined the effects of the fast-acting, β 1 selective blocker esmolol on systemic hemodynamics and leg muscle O 2 saturation (near infrared spectroscopy, NIRS) during submaximal leg ergometry. Our main hypothesis was that esmolol would augment exercise-induced reductions in leg muscle O 2 saturation. Eight healthy adults (6 men, 2 women; 23-67 year) performed light and moderate intensity bouts of recumbent leg cycling before (PRE), during (β 1 -blocked), and 45 min following (POST) intravenous infusion of esmolol. Oxygen uptake, heart rate (HR), BP, and O 2 saturation (SmO 2 ) of the vastus lateralis (VL) and medial gastrocnemius (MG) muscles were measured continuously. Esmolol attenuated the increases in HR and systolic BP during light (-12 ± 9 bpm and -26 ± 12 mmHg vs. PRE) and moderate intensity (-20 ± 10 bpm and -40 ± 18 mmHg vs. PRE) cycling (all P < 0.01). Exercise-induced reductions in SmO 2 occurred to a greater extent during the β 1 -blockade trial in both the VL (P = 0.001 vs. PRE) and MG muscles (P = 0.022 vs. PRE). HR, SBP and SmO 2 were restored during POST (all P < 0.01 vs. β 1 -blocked). In conclusion, esmolol rapidly and reversibly increases O 2 extraction within exercising muscles of healthy humans., (© 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The purpose of this study was to investigate blood pressure (BP) and leg skeletal muscle oxygen saturation (Smo 2 ) during treadmill walking in patients with peripheral artery disease (PAD) and healthy subjects. Eight PAD patients (66 ± 8 yr, 1 woman) and eight healthy subjects (65 ± 7 yr, 1 woman) walked on a treadmill at 2 mph (0.89 m/s). The incline increased by 2% every 2 min, from 0 to 15% or until maximal discomfort. BP was measured every 2 min with an auscultatory cuff. Heart rate (HR) was recorded continuously with an ECG. Smo 2 in the gastrocnemius muscle was measured on each leg using near-infrared spectroscopy. The change in systolic BP from seated to peak walking time (PWT) was greater in PAD (healthy: 23 ± 9 vs. PAD: 44 ± 19 mmHg, P = 0.007). HR was greater in PAD patients compared with controls at PWT ( P = 0.011). The reduction in Smo 2 (PWT - seated) was greater in PAD (healthy: 15 ± 12 vs. PAD: 49 ± 5%, P < 0.001) in the most affected leg and in the least affected leg (healthy: 12 ± 11 vs. PAD: 32 ± 18%, P = 0.003). PAD patients have an exaggerated decline in leg Smo 2 during walking compared with healthy subjects, which may elicit the exaggerated rise in BP and HR during walking in PAD. NEW & NOTEWORTHY This is the first study to simultaneously measure skeletal muscle oxygen saturation and blood pressure (BP) during treadmill exercise in patients with peripheral arterial disease. We found that BP and leg deoxygenation responses to slow-paced, graded treadmill walking are greater in patients with peripheral arterial disease compared with healthy subjects. These data may help explain the high cardiovascular risk in patients with peripheral arterial disease., (Copyright © 2017 the American Physiological Society.)

During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia is not clear. In this study, we simultaneously measured noninvasive indexes of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand [i.e., rate pressure product (RPP) = heart rate × systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared with nonselective β-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously, and RPP was calculated. Changes in parameters from baseline were compared with paired t -tests. Esmolol (Δ = 3296 ± 1204) and propranolol (Δ = 2997 ± 699) caused similar reductions in peak RPP compared with saline (Δ = 5384 ± 1865). In support of our hypothesis, ΔCBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 vs. 4.5 ± 1.6 cm/s; P = 0.002). This effect was also evident when normalizing ΔCBV to ΔRPP. In summary, not only does selective β1 blockade reduce myocardial oxygen demand during exercise, but it also unveils β2-receptor-mediated coronary exercise hyperemia. NEW & NOTEWORTHY In this study, we evaluated the role of vascular β1 vs. β2 receptors in coronary exercise hyperemia in a single-blind, randomized, crossover study in healthy men. In response to isometric handgrip exercise, blood flow velocity in the left anterior descending coronary artery was significantly greater with esmolol compared with propranolol. These findings increase our understanding of the individual and combined roles of coronary β1 and β2 adrenergic receptors in humans., (Copyright © 2017 the American Physiological Society.)

Peripheral artery disease (PAD) is an atherosclerotic vascular disease that affects 200 million people worldwide. Although PAD primarily affects large arteries, it is also associated with microvascular dysfunction, an exaggerated blood pressure (BP) response to exercise, and high cardiovascular mortality. We hypothesized that fatiguing plantar flexion exercise that evokes claudication elicits a greater reduction in skeletal muscle oxygenation (SmO 2 ) and a higher rise in BP in PAD compared with age-matched healthy subjects, but low-intensity steady-state plantar flexion elicits similar responses between groups. In the first experiment, eight patients with PAD and eight healthy controls performed fatiguing plantar flexion exercise (from 0.5 to 7 kg for up to 14 min). In the second experiment, seven patients with PAD and seven healthy controls performed low-intensity plantar flexion exercise (2.0 kg for 14 min). BP, heart rate (HR), and SmO 2 were measured continuously using near-infrared spectroscopy (NIRS). SmO 2 is the ratio of oxygenated hemoglobin to total hemoglobin, expressed as a percent. At fatigue, patients with PAD had a greater increase in mean arterial BP (18 ± 2 vs. vs. 10 ± 2 mmHg, P = 0.029) and HR (14 ± 2 vs. 6 ± 2 beats/min, P = 0.033) and a greater reduction in SmO 2 (-54 ± 10 vs. -12 ± 4%, P = 0.001). However, both groups had similar physiological responses to low-intensity, nonpainful plantar flexion exercise. These data suggest that patients with PAD have altered oxygen uptake and/or utilization during fatiguing exercise coincident with an augmented BP response. NEW & NOTEWORTHY In this laboratory study, patients with peripheral artery disease performed plantar flexion exercise in the supine posture until symptoms of claudication occurred. Relative to age- and sex-matched healthy subjects we found that patients had a higher blood pressure response, a higher heart rate response, and a greater reduction in skeletal muscle oxygenation as determined by near-infrared spectroscopy. Our data suggest that muscle ischemia contributes to the augmented exercise pressor reflex in peripheral artery disease., (Copyright © 2017 the American Physiological Society.)

Purpose: To evaluate the dynamic characteristics of T2* -weighted signal change in exercising skeletal muscle of healthy subjects and peripheral artery disease (PAD) patients under a low-intensity exercise paradigm., Materials and Methods: Nine PAD patients and nine age- and sex-matched healthy volunteers underwent a low-intensity exercise paradigm while magnetic resonance imaging (MRI) (3.0T) was obtained. T2*-weighted signal time-courses in lateral gastrocnemius, medial gastrocnemius, soleus, and tibialis anterior were acquired and analyzed. Correlations were performed between dynamic T2*-weighted signal and changes in heart rate, mean arterial pressure, leg pain, and perceived exertion., Results: A significant signal decrease was observed during exercise in soleus and tibialis anterior of healthy participants (P = 0.0007-0.04 and 0.001-0.009, respectively). In PAD, negative signals were observed (P = 0.008-0.02 and 0.003-0.01, respectively) in soleus and lateral gastrocnemius during the early exercise stage. Then the signal gradually increased above the baseline in the lateral gastrocnemius during and after exercise in six of the eight patients who completed the study. This signal increase in patients' lateral gastrocnemius was significantly greater than in healthy subjects' during the later exercise stage (two-sample t-tests, P = 0.001-0.03). Heart rate and mean arterial pressure responses to exercise were significantly higher in PAD than healthy subjects (P = 0.036 and 0.008, respectively) and the patients experienced greater leg pain and exertion (P = 0.006 and P = 0.0014, respectively)., Conclusion: During low-intensity exercise, there were different dynamic T2*-weighted signal behavior in the healthy and PAD exercising muscles., Level of Evidence: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:40-48., (© 2016 International Society for Magnetic Resonance in Medicine.)

Despite its widespread clinical use, the β 1 -adrenergic receptor antagonist esmolol hydrochloride is not commonly used in human physiology research, and the effective dose of esmolol (compared with the nonselective β-blocker propranolol) is unclear. In four separate studies we used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate (HR)-lowering effect of esmolol compared with propranolol and saline in healthy humans. In cohort 1 , both esmolol (ΔHR 57 ± 6 beats/min) and propranolol (ΔHR 56 ± 7 beats/min) attenuated exercise tachycardia compared with saline (ΔHR 88 ± 17 beats/min). In cohort 2 , we found that the HR response to exercise was similar at 5 min (ΔHR 57 ± 9 beats/min) and 60 min (ΔHR 55 ± 9 beats/min) after initiation of the esmolol maintenance infusion. In cohort 3 , we confirmed that the HR-lowering effect of esmolol disappeared 45 min after termination of the maintenance infusion. In cohort 4 , changes in femoral blood flow and hematological parameters in response to epinephrine infusion were not different between esmolol and saline infusion, indicating that our esmolol infusion paradigm does not block β 2 -receptors. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks β 1 -receptors in healthy humans. Additionally, β 1 -receptors remain blocked 60 min later if a maintenance infusion of ~0.2 mg·kg total body mass -1 ·min- 1 continues. The current data lay the foundation for future studies to evaluate β 1 - vs. β 2 -receptor control of the circulation in humans. NEW & NOTEWORTHY We used cycle ergometry exercise and infusions of isoproterenol and epinephrine to test the heart rate-lowering effect of esmolol compared with propranolol and saline in healthy humans. Collectively, our data indicate that infusion of ~160 mg of esmolol (range 110-200 mg in the 5 min before exercise) acutely and selectively blocks β1-adrenergic receptors. These infusion parameters can be used in future experiments to evaluate β1- vs. β2-receptor control of the circulation in humans., (Copyright © 2017 the American Physiological Society.)

Background: Peripheral arterial disease (PAD) is an atherosclerotic vascular disease that affects over 200 million people worldwide. The hallmark of PAD is ischemic leg pain and this condition is also associated with an augmented blood pressure response to exercise, impaired vascular function, and high risk of myocardial infarction and cardiovascular mortality. In this study, we tested the hypothesis that coronary exercise hyperemia is impaired in PAD., Methods: Twelve patients with PAD and no overt coronary disease (65 ± 2 years, 7 men) and 15 healthy control subjects (64 ± 2 years, 9 men) performed supine plantar flexion exercise (30 contractions/min, increasing workload). A subset of subjects (n = 7 PAD, n = 8 healthy) also performed isometric handgrip exercise (40% of maximum voluntary contraction to fatigue). Coronary blood velocity in the left anterior descending artery was measured by transthoracic Doppler echocardiography; blood pressure and heart rate were monitored continuously., Results: Coronary blood velocity responses to 4 min of plantar flexion exercise (PAD: Δ2.4 ± 1.2, healthy: Δ6.0 ± 1.6 cm/sec, P = 0.039) and isometric handgrip exercise (PAD: Δ8.3 ± 4.2, healthy: Δ16.9 ± 3.6, P = 0.033) were attenuated in PAD patients., Conclusion: These data indicate that coronary exercise hyperemia is impaired in PAD, which may predispose these patients to myocardial ischemia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

INTRODUCTION Patients are interested in receiving text messages (texts) related to their health care. However, anecdotes are emerging of associated problems and it is possible that many of the potential pitfalls are not recognised. AIM To assess clinicians' attitudes and behaviours towards text messaging (texting) with patients. METHODS A voluntary, anonymous, online survey was created and distributed to general practitioners and physiotherapists in New Zealand and to Sports Medicine Fellows and Sports Medicine Registrars in New Zealand and Australia. RESULTS In total, 322 clinicians completed the survey. Texting behaviours relating to accuracy, privacy and security were identified. A range of sensitive and important medical information was frequently conveyed and at times forwarded to third parties. The clinicians generally felt uneasy communicating this way and some felt pressured into it. Most thought that guidelines are insufficient and that they had not received sufficient education on the issues. Most were interested in further education. CONCLUSION This study has demonstrated frequent texting between clinicians and patients. It has highlighted potential risks to the privacy, accuracy and security of medical information. Current guidelines and education may be insufficient. Clinicians were interested in receiving readily available best practice guidelines and education regarding texting.

Blood-oxygen-level-dependent magnetic resonance imaging (BOLD MRI) has the potential to quantify skeletal muscle oxygenation with high temporal and high spatial resolution. The purpose of this study was to characterize skeletal muscle BOLD responses during steady-state plantar flexion exercise (i.e., during the brief rest periods between muscle contraction). We used three different imaging modalities (ultrasound of the popliteal artery, BOLD MRI, and near-infrared spectroscopy [NIRS]) and two different exercise intensities (2 and 6 kg). Six healthy men underwent three separate protocols of dynamic plantar flexion exercise on separate days and acute physiological responses were measured. Ultrasound studies showed the percent change in popliteal velocity from baseline to the end of exercise was 151 ± 24% during 2 kg and 589 ± 145% during 6 kg. MRI studies showed an abrupt decrease in BOLD signal intensity at the onset of 2 kg exercise, indicating deoxygenation. The BOLD signal was further reduced during 6 kg exercise (compared to 2 kg) at 1 min (-4.3 ± 0.7 vs. -1.2 ± 0.4%, P < 0.001). Similarly, the change in the NIRS muscle oxygen saturation in the medial gastrocnemius was -11 ± 4% at 2 kg and -38 ± 11% with 6 kg (P = 0.041). In conclusion, we demonstrate that BOLD signal intensity decreases during plantar flexion and this effect is augmented at higher exercise workloads., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Myocardial oxygen supply and demand mismatch is fundamental to the pathophysiology of ischemia and infarction. The sympathetic nervous system, through α-adrenergic receptors and β-adrenergic receptors, influences both myocardial oxygen supply and demand. In animal models, mechanistic studies have established that adrenergic receptors contribute to coronary vascular tone. The purpose of this laboratory study was to noninvasively quantify coronary responses to adrenergic receptor stimulation in humans. Fourteen healthy volunteers (11 men and 3 women) performed isometric handgrip exercise to fatigue followed by intravenous infusion of isoproterenol. A subset of individuals also received infusions of phenylephrine (n = 6), terbutaline (n = 10), and epinephrine (n = 4); all dosages were based on fat-free mass and were infused slowly to achieve steady-state. The left anterior descending coronary artery was visualized using Doppler echocardiography. Beat-by-beat heart rate (HR), blood pressure (BP), peak diastolic coronary velocity (CBVpeak), and coronary velocity time integral were calculated. Data are presented as M ± SD Isometric handgrip elicited significant increases in BP, HR, and CBVpeak (from 23.3 ± 5.3 to 34.5 ± 9.9 cm/sec). Isoproterenol raised HR and CBVpeak (from 22.6 ± 4.8 to 43.9 ± 12.4 cm/sec). Terbutaline and epinephrine evoked coronary hyperemia whereas phenylephrine did not significantly alter CBVpeak. Different indices of coronary hyperemia (changes in CBVpeak and velocity time integral) were significantly correlated (R = 0.803). The current data indicate that coronary hyperemia occurs in healthy humans in response to isometric handgrip exercise and low-dose, steady-state infusions of isoproterenol, terbutaline, and epinephrine. The contribution of β1 versus β2 receptors to coronary hyperemia remains to be determined. In this echocardiographic study, we demonstrate that coronary blood flow increases when β-adrenergic receptors are stimulated (i.e., during exercise and different intravenous infusions). Our infusion paradigms and beat-by-beat imaging methodologies can be used in future studies to evaluate age-, sex-, and disease- differences in adrenergic control of coronary blood flow., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

The current experiment examined the factors that determine acquisition for elements of highly structured serial patterns. Three groups of rats were trained on three patterns with parallel rule-based hierarchical structure, but with 3-, 4-, or 5-element chunks, each with a final violation element. Once rats mastered their patterns, probe patterns were introduced to answer several questions. To assess the extent to which the learned response pattern depended on intrachamber location cues for anticipating different element types, Spatial Shift Probes shifted the starting lever of patterns to locations that positioned chunk boundaries where they had never been experienced during training. To assess the extent to which a phrasing cue is necessary for rats to perform a chunk-boundary response, a Cue Removal Probe tested whether rats would produce a chunk-boundary response in the correct serial position if the phrasing cue was omitted. To assess the extent to which cues from multiple trials leading up to the violation element are required to anticipate the violation element, Multiple-Item Memory Probes required rats to make an unexpected response on one of the elements in the last two chunks of the pattern prior to the violation element. The results indicated that rats used multiple concurrent learning and memory processes to master serial patterns, including discrimination learning, rule learning, encoding of chunk length, and multiple-item memories., (© 2016 Society for the Experimental Analysis of Behavior.)

Objective: To report on the progress of an ongoing research collaboration on magnetic resonance imaging (MRI) in juvenile idiopathic arthritis (JIA) and describe the proceedings of a meeting, held prior to Outcome Measures in Rheumatology (OMERACT) 12, bringing together the OMERACT MRI in JIA working group and the Health-e-Child radiology group. The goal of the meeting was to establish agreement on scoring definitions, locations, and scales for the assessment of MRI of patients with JIA for both large and small joints., Methods: The collaborative work process included premeeting surveys, presentations, group discussions, consensus on scoring methods, pilot scoring, conjoint review, and discussion of a future research agenda., Results: The meeting resulted in preliminary statements on the MR imaging protocol of the JIA knee and wrist and determination of the starting point for development of MRI scoring systems based on previous studies. It was also considered important to be descriptive rather than explanatory in the assessment of MRI in JIA (e.g., "thickening" instead of "hypertrophy"). Further, the group agreed that well-designed calibration sessions were warranted before any future scoring exercises were conducted., Conclusion: The combined efforts of the OMERACT MRI in JIA working group and Health-e-Child included the assessment of currently available material in the literature and determination of the basis from which to start the development of MRI scoring systems for both the knee and wrist. The future research agenda for the knee and wrist will include establishment of MRI scoring systems, an atlas of MR imaging in healthy children, and MRI protocol requisites.

Exposure to hypoxia is associated with cognitive impairment, mediated by cerebral deoxygenation. This can be problematic for individuals who perform mental tasks at high altitude. Eight healthy men completed two experimental trials consisting of 5h of exposure to normobaric hypoxia (12.5% O2). In one of the experimental trials (Hypoxia) subjects remained resting in a seated position the entire 5h; in the other experimental trial (Hypoxia and Exercise) subjects rested 2h, cycled for 1h at constant wattage (workload equivalent to 50% of altitude adjusted VO2max), then rested the last 2h. Cerebral oxygenation was measured continuously via near-infrared spectroscopy and cognitive performance was assessed by Trail Making Test A and B. Cerebral oxygenation and cognitive performance both were impaired during exposure to hypoxia. In the Hypoxia and Exercise trial, subjects experienced further declinations in cerebral oxygenation without concomitant decreases in cognitive function. These data demonstrate that cognitive function declines during exposure to normobaric hypoxia and this decline is not exacerbated by low intensity exercise., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Venous saline infusions in an arterially occluded forearm evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP). We hypothesized that the application of suction to the human limbs would activate this venous distension reflex and raise sympathetic outflow. We placed airtight pressure tanks and applied 100 mmHg negative pressure to an arterially occluded limb (occlusion and suction, O&S) to induce tissue deformation without fluid translocation. BP, heart rate (HR), and MSNA were assessed in 19 healthy subjects during 2 min of arm or leg O&S. Occlusion without suction served as a control. During a separate visit, saline (5% forearm volume) was infused into veins of the arterially occluded arm (n = 13). The O&S increased limb circumference, MSNA burst rate (arm: Δ6.7 ± 0.7; leg: Δ6.8 ± 0.7 bursts/min), and total activity (arm: Δ199 ± 14; leg: Δ172 ± 22 units/min) and BP (arm: Δ4.3 ± 0.3; leg: Δ9.4 ± 1.4 mmHg) from the baseline. The MSNA and BP responses during arm O&S correlated with those during leg O&S. Occlusion alone had no effect on MSNA and BP. MSNA (r = 0.607) responses during arm O&S correlated with those evoked by the saline infusion into the arm. These correlations suggest that sympathetic activation during limb O&S is likely, at least partially, to be evoked via the venous distension reflex. These data suggest that suction of an occluded limb evokes sympathetic activation and that the limb venous distension reflex exists in arms and legs of normal humans., (Copyright © 2015 the American Physiological Society.)

Prostanoids are produced during skeletal muscle contraction and subsequently stimulate muscle afferent nerves, thereby contributing to the exercise pressor reflex. Humans with peripheral arterial disease (PAD) have an augmented exercise pressor reflex, but the metabolite(s) responsible for this augmented response is not known. We tested the hypothesis that intravenous injection of ketorolac, which blocks the activity of cyclooxygenase, would attenuate the rise in mean arterial blood pressure (MAP) and heart rate (HR) evoked by plantar flexion exercise. Seven PAD patients underwent 4 min of single-leg dynamic plantar flexion (30 contractions/min) in the supine posture (workload: 0.5-2.0 kg). MAP and HR were measured on a beat-by-beat basis; changes from baseline in response to exercise were determined. Ketorolac did not affect MAP or HR at rest. During the first 20 s of exercise with the most symptomatic leg, ΔMAP was significantly attenuated by ketorolac (2 ± 2 mmHg) compared with control (8 ± 2 mmHg, P = 0.005), but ΔHR was similar (6 ± 2 vs. 5 ± 1 beats/min). Importantly, patients rated the exercise bout as "very light" to "fairly light," and average pain ratings were 1 of 10. Ketorolac had no effect on perceived exertion or pain ratings. Ketorolac also had no effect on MAP or HR in seven age- and sex-matched healthy subjects who performed a similar but longer plantar flexion protocol (workload: 0.5-7.0 kg). These data suggest that prostanoids contribute to the augmented exercise pressor reflex in patients with PAD., (Copyright © 2015 the American Physiological Society.)

Epidemiologic data suggest there are seasonal variations in the incidence of severe cardiac events with peak levels being evident in the winter. Whether autonomic indices including muscle sympathetic nerve activity (MSNA) vary with season remains unclear. In this report, we tested the hypothesis that resting MSNA varies with the seasons of the year with peak levels evident in the winter. We analyzed the supine resting MSNA in 60 healthy subjects. Each subject was studied during two, three, or four seasons (total 237 visits). MSNA burst rate in the winter (21.0 ± 6.8 burst/min, mean ± SD) was significantly greater than in the summer (13.5 ± 5.8 burst/min, P < 0.001), the spring (17.1 ± 9.0 burst/min, P = 0.03), and the fall (17.9 ± 7.7 burst/min, P = 0.002). There was no significant difference in MSNA for other seasonal comparisons. The results suggest that resting sympathetic nerve activity varies along the seasons, with peak levels evident in the winter. We speculate that the seasonal changes in sympathetic activity may be a contribution to the previously observed seasonal variations in cardiovascular morbidity and mortality., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

We recently demonstrated that postmenopausal women have an augmented blood pressure response to voluntary apnea compared to premenopausal women. Both obstructive sleep apnea (OSA) and healthy aging are associated with increased oxidative stress, which may impair cardiovascular function. Restoring physiological responses could have clinical relevance since transient surges in blood pressure are thought to be an important stimulus for end-organ damage in aging and disease. We tested the hypothesis that acute antioxidant infusion improves physiological responses to voluntary apnea in healthy postmenopausal women (n = 8, 64 ± 2 year). We measured beat-by-beat mean arterial pressure (MAP), heart rate (HR), and brachial artery blood flow velocity (BBFV, Doppler ultrasound) following intravenous infusion of normal saline and ascorbic acid (~3500 mg). Subjects performed maximal voluntary end-expiratory apneas and changes (Δ) from baseline were compared between infusions. The breath hold duration and oxygen saturation nadir were similar between saline (29 ± 6 sec, 94 ± 1%) and ascorbic acid (29 ± 5 sec, 94 ± 1%). Ascorbic acid attenuated the pressor response to voluntary apnea (ΔMAP: 6 ± 2 mmHg) as compared to saline (ΔMAP: 12 ± 2 mmHg, P = 0.034) and also attenuated forearm vasoconstriction (ΔBBFV: 4 ± 9 vs. -12 ± 7%, P = 0.049) but did not affect ΔHR. We conclude that ascorbic acid lowers the blood pressure response to voluntary apnea in postmenopausal women by inhibiting vasoconstriction in the limb vasculature. Whether ascorbic acid has similar effects in OSA patients remains to be prospectively tested., (© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Patients with coronary artery disease have attenuated coronary vasodilator responses to physiological stress, which is partially attributed to a β-adrenergic receptor (β-AR)-mediated mechanisms. Whether β-ARs contribute to impaired coronary vasodilation seen with healthy aging is unknown. The purpose of this study was to investigate the role of β-ARs in coronary exercise hyperemia in healthy humans. Six young men (26 ± 1 yr) and seven older men (67 ± 4 yr) performed isometric handgrip exercise at 30% maximal voluntary contraction for 2 min after receiving intravenous propranolol, a β-AR antagonist, and no treatment. Isoproterenol, a β-AR agonist, was infused to confirm the β-AR blockade. Blood pressure and heart rate were monitored continuously, and coronary blood flow velocity (CBV, left anterior descending artery) was measured by transthoracic Doppler echocardiography. Older men had an attenuated ΔCBV to isometric exercise (3.8 ± 1.3 vs. 9.7 ± 2.1 cm/s, P = 0.02) compared with young men. Propranolol decreased the ΔCBV at peak handgrip exercise in young men (9.7 ± 2.1 vs. 2.7 ± 0.9 cm/s, P = 0.008). However, propranolol had no effect on ΔCBV in older men (3.8 ± 1.3 vs. 4.2 ± 1.9 cm/s, P = 0.9). Older men also had attenuated coronary hyperemia to low-dose isoproterenol. These data indicate that β-AR control of coronary blood flow is impaired in healthy older men., (Copyright © 2014 the American Physiological Society.)