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The effects of nitroglycerin (glyceryl trinitrate, GTN) on baroreflex sensitivity (BRS) are incompletely understood. Moreover, there are no reports evaluating the acute responses in both the sympathetic BRS (SBRS) and the cardiovagal BRS (CBRS) to the administration of sublingual GTN. We hypothesized that sublingual GTN modulates both CBRS and SBRS. In 10 healthy subjects, beat-to-beat heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated from the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. These variables were assessed during baseline, during 3rd--6th min (post A), and 7th--10th min (post B) after GTN administration. Two min after GTN administration, MSNA increased significantly and remained significantly elevated during recording. Compared with baseline, CBRS decreased signifi- cantly (post A: 12.9 ± 1.6 to 7.1 ± 1.0 ms/mmHg, P < 0.05), whereas SBRS increased significantly (post A: 0.8 ± 0.2 to 1.5 ± 0.2 units·beat-1·mmHg-1, P < 0.05) with an upward shift of the operating point. There were no differences in these variables between posts A and B. A clinical dose of GTN increased MSNA rapidly through effects on both CBRS and SBRS. These effects should be kept in mind when nitrates are used to clinically treat chest pain and acute coronary syndromes and used as vasodilators in experimental settings. [ABSTRACT FROM AUTHOR]

Venous saline infusions in an arterially occluded forearm evoke reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) in humans (venous distension reflex). It is unclear if the inputs from metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) would modify the venous distension reflex. We hypothesized that muscle metaboreceptor stimulation might augment the venous distension reflex. BP (Finapres), heart rate (ECG), and MSNA (microneurography) were assessed in 18 young healthy subjects. In trial A, saline (5% forearm volume) was infused into the veins of an arterially occluded arm (nonhandgrip trial). In trial B, subjects performed 2-min static handgrip followed by postexercise circulatory occlusion (PECO) of the arm. During PECO, saline was infused into the veins of the arm (handgrip trial). In trial A, the infusion increased MSNA and BP as expected (both P < 0.001). In trial B, handgrip significantly raised MSNA, BP, and venous lactic acid concentrations. Venous saline infusion during PECO further raised MSNA and BP (both P < 0.001). The changes in MSNA (Δ8.6 ± 1.5 to Δ10.6 ± 1.8 bursts/min, P = 0.258) and mean arterial pressure (P = 0.844) evoked by the infusion during PECO were not significantly different from those in the nonhandgrip trial. These observations indicate that venous distension reflex responses are preserved during sympathetic activation mediated by the muscle metaboreflex. [ABSTRACT FROM AUTHOR]

Earlier reports suggest that limb venous distension evokes reflex increases in muscle sympathetic nerve activity (MSNA) and blood pressure (BP) (i.e., venous distension reflex). Our recent report also shows that suction of arterially occluded limb evokes venous distension reflex. We postulate that the venous distension reflex contributes to autonomic responses to orthostatic stress. In this study, we hypothesized that orthostatic tolerance would be linked to the MSNA response seen with lower limb suction. Fifteen healthy subjects were tested in the supine position. Negative pressure (-100 mmHg) was applied on an arterially occluded lower limb for 2 min. MSNA from the peroneal nerve in the limb not exposed to suction, ECG, and BP (Finometer) was recorded throughout the study. Limb occlusion without suction was used as a control trial. In a separate visit, the individual's orthostatic tolerance was assessed using a graded lower body negative pressure (LBNP) tolerance test. Mean arterial BP and MSNA (18.6 ± 1.9 to 23.6 ± 2.0 bursts/min) significantly (both P < 0.05) increased during limb suction. Orthostatic tolerance index positively correlated (R = 0.636, P = 0.011) with the MSNA response seen with suction during occlusion. Since the venous distension reflex strength correlates with the level of orthostatic tolerance, we speculate that lower-limb venous distension reflex engagement increases the sympathetic responses during orthostatic challenge and serves to maintain BP with postural stress. [ABSTRACT FROM AUTHOR]

Low-dose aspirin inhibits thromboxane production and augments the sensitivity of carotid baroreflex (CBR) control of heart rate (HR) during concurrent muscle mechanoreflex and metaboreflex activation in healthy young humans. However, it is unknown how aging affects this response. Therefore, the effect of low-dose aspirin on carotid-cardiac baroreflex sensitivity during muscle mechanoreflex with and without metaboreflex activation in healthy older humans was examined. Twelve older subjects (6 men and 6 women, mean age: 62 ± 1 yr) performed two trials during two visits preceded by 7 days of low-dose aspirin (81 mg) or placebo. One trial involved 3 min of passive calf stretch (mechanoreflex) during 7.5 min of limb circulatory occlusion (CO). In another trial, CO was preceded by 1.5 min of 70% maximal voluntary contraction isometric calf exercise (mechanoreflex and metaboreflex). HR (ECG) and mean arterial blood pressure (MAP; Finometer) were recorded. CBR function was assessed using rapid neck pressure application (+40 to -80 mmHg. Aspirin significantly decreased baseline thromboxane B2 production by 83 ± 4% (P < 0.05) but did not affect 6-keto-PGF1α After aspirin, CBR-HR maximal gain and operating point gain were significantly higher during stretch with metabolite accumulation compared with placebo (maximal gain: -0.23 ± 0.03 vs. -0.14 ± 0.02 and operating point gain: -0.11 ± 0.03 vs. -0.04 ± 0.01 beats7#8901;min-1-mmHg-1 for aspirin and placebo, respectively, P < 0.05). In conclusion, these findings suggest that low-dose aspirin augments CBR-HR sensitivity during concurrent muscle mechanoreflex and metaboreflex activation in healthy older humans. This increased sensitivity appears linked to reduced thromboxane sensitization of muscle mechanoreceptors, which consequently improves CBR-HR control. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the effects of repeated moderate heat exposure (RMHE) on muscle sympathetic nerve activity (MSNA) and cardiovascular control in healthy individuals. METHODS: We performed the RMHE with 4 weeks (5 days/week) warm baths (~40 deg C) for 30 min in 9 healthy older (59 ± 2 yrs) volunteers. Hemodynamic variables and MSNA were examined in a laboratory at ~23 deg C prior, 1 day after and 1 week after end of RMHE. A cold pressor test and handgrip exercise were performed during the testing sessions. RESULTS: Under normothermic conditions, the resting MSNA burst rate (prior, post, post 1-wk: 31.6 ± 2.0, 25.2 ± 2.0, 27.7 ± 1.7 bursts/min; P < 0.001) and burst incidence (P < 0.001) significantly decreased after RMHE. Moreover, the resting heart rate significantly decreased after RMHE (62.3 ± 1.6, 59.5 ± 2.0, 58.2 ± 1.6 beats/min, P < 0.05). The LF/HF ratio also decreased after RMHE. The sensitivity of baroreflex control of MSNA and heart rate were not altered by RMHE, although the baroreflex operating point was reset. The MSNA and hemodynamic responses (i.e. changes) to handgrip exercise or the cold pressor test were not altered. CONCLUSIONS: In this age group, RMHE evoked by warm baths decreases resting sympathetic activity and HR, which can be considered as beneficial effects. The mechanism(s) should be examined in future studies.Supported by National Institutes of Health Grants MPI R01 HL141198 (Li and Cui) and UL1 TR002014 (Sinoway). [ABSTRACT FROM AUTHOR]

R1908 --> 753.1 --> To date, more than 46 million people in the United States have contracted the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), which causes COVID‐19. Over 700 thousand total cases have been linked to American colleges and universities. Post‐acute sequelae of SARS‐CoV‐2 infection may affect varied systems. It was reported that sympathetic nerve activity following SARS‐CoV‐2 infection was elevated in young individuals. Cardiovascular autonomic function post‐acute SARS‐CoV‐2 infection in other populations such as athletes, however, has not been thoroughly investigated. Collegiate athletes are a unique population given that they might have a high level of physical fitness before the infection. The present study examined 16 collegiate athletes (12 men and 4 women, age: 20±1 yrs, height: 181±10 cm, weight: 81±18 kg) who were evaluated ~2 weeks after testing positive for SARS‐CoV‐2 by polymerase chain reaction assay. These subjects were asymptomatic or with mild/moderate symptoms during infection. None of the subjects had been hospitalized for COVID‐19 and all subjects were asymptomatic at the time of the study. Beat‐by‐beat blood pressure (BP) with Finometer, and heart rate (HR) from ECG were recorded during 10 minutes of supine rest, Valsalva maneuver, slow breathing (6 breaths/min), handgrip exercise, and 10 minutes of standing. BP, HR, heart rate variability (HRV), and cardiac baroreflex sensitivity (CBRS), and venous blood aldosterone and renin levels were analyzed. The vagal tone index from HRV in 3 of 16 athletes was lower than normative values. The responses in BP to Valsalva maneuver during phases IIa (i.e., "early") and IIb (i.e., "late") were mildly abnormal in 4 athletes and moderately abnormal in one athlete. The Valsalva ratio was below the normal range in 6 athletes. In response to slow breathing, the respiratory sinus arrhythmia amplitude was below the normal range in 3 athletes. In response to handgrip exercise, one athlete had an atypical response where BP decreased while HR was increased from baseline. Three of the subjects were unable to tolerate an orthostatic challenge for 10 minutes. Four out of 16 athletes had abnormally elevated renin activity and 1 out 16 elevated aldosterone levels. It is important to note that while several athletes had abnormal responses to the various autonomic tests, these abnormalities did not correlate with symptoms seen during the infection. Our data suggest that SARS‐CoV‐2 infection may reduce parasympathetic and increase sympathetic tone and may contribute to the autonomic disfunction associated in a subset of collegiate athletes even after recovering from COVID‐19. This study provides further evidence for potential long‐term cardiovascular autonomic effects of Covid‐19 infection even in healthy young trained athletes. Further studies with a larger patient population as well as suitable healthy control subjects are warranted. [ABSTRACT FROM AUTHOR]

It is suggested that mechanoreceptors in muscle play an important role in the exercise pressor reflex. However, it has not been verified whether isolated stimulation of the mechanoreceptors can induce responses in muscle sympathetic nerve activity (MSNA) in young healthy individuals. We tested the hypothesis that passive stretch of muscle can evoke an increase in MSNA in healthy individuals. In 12 young subjects, leg calf muscles were passively stretched, or actively contracted for 5 s followed by a 15–25 s (random length) relaxation period. Stretch and contraction were each repeated 25 times. MSNA, heart rate and blood pressure were analysed, and averaged according to the onset of the force on a beat-by-beat basis. At the 1st to the 3rd heart beat from the onset of stretch, MSNA (199 ± 30%, P < 0.05) as well as heart rate (102.5 ± 0.7%, P < 0.05) increased transiently but significantly from the prior stretch baseline (100%), followed (from 3rd to 7th beat from the onset of stretch) by a transient increase in mean blood pressure (101.9 ± 0.3%, P < 0.05) from the baseline. Similar response patterns were observed during active muscle contractions. The present data show that MSNA responses to isolated stimulation of mechanoreceptors are measurable. Because of baroreflex engagement, the magnitude of the response is small and transient, and the haemodynamic consequences using this protocol may be limited. [ABSTRACT FROM AUTHOR]

Skeletal muscle perfusion and oxygenation are commonly evaluated using Doppler ultrasound and near-infrared spectroscopy (NIRS) techniques. However, a recently developed magnetic resonance imaging (MRI) sequence, termed PIVOT, permits the simultaneous collection of skeletal muscle perfusion and T2* (an index of skeletal muscle oxygenation). To determine the level of agreement between PIVOT, Doppler ultrasound, and NIRS-based assessments of skeletal muscle perfusion and oxygenation. Twelve healthy volunteers (8 females, 25 ± 3 years, 170 ± 11 cm, 71.5 ± 8.0 kg) performed six total reactive hyperemia protocols. During three of these reactive hyperemia protocols, Tissue Saturation Index (TSI) and oxygenated hemoglobin (O 2 Hb) were recorded from the medial gastrocnemius (MG) and tibialis anterior (TA), and blood flow velocity was recorded from the popliteal artery (BFv pop) via Doppler Ultrasound. The other three trials were performed inside the bore of a 3 T MRI scanner, and the PIVOT sequence was used to assess perfusion (PIVOT perf) and oxygenation (T2*) of the medial gastrocnemius and tibialis anterior muscles. Positive incremental areas under the curve (iAUC) and times to peak (TTP) were calculated for each variable, and the level of agreement between collection methods was evaluated via Bland-Altman analyses and Spearman's Rho correlation analyses. The only significant bivariate relationships observed were between the T2* vs. TSI iAUC and PIVOT perf vs. BFv pop values recorded from the MG. Significant mean differences were observed for all comparisons (all P ≤ 0.038), and significant proportional biases were observed for the PIVOT perf vs. tHb TTP (R2 = 0.848, P < 0.001) and T2* vs. TSI TTP comparisons in the TA (R2 = 0.488, P = 0.011), and the PIVOT perf vs. BFv pop iAUC (R2 = 0.477, P = 0.013) and time to peak (R2 = 0.851, P < 0.001) comparisons in the MG. Our findings suggest that the PIVOT technique has, at best, a moderate level of agreement with Doppler ultrasound and NIRS assessment methods and is subject to significant proportional bias. These findings do not challenge the accuracy of either measurement technique but instead reflect differences in the vascular compartments, sampling volumes, and parameters being evaluated. • Recent studies have used the MRI "PIVOT" sequence to quantify leg muscle perfusion and oxygenation. • This study determined the level of agreement between PIVOT, near-infrared spectroscopy, and Doppler ultrasound. • PIVOT demonstrates, at best, moderate levels of agreement with Doppler and NIRS. • This provides valuable information for future investigations planning to use the PIVOT MRI technique. [ABSTRACT FROM AUTHOR]

Preclinical models indicate that amiloride (AMD) reduces baroreflex sensitivity and perturbs homeostatic blood pressure (BP) regulation. However, it remains unclear whether these findings translate to humans. This study investigated whether oral administration of AMD reduces spontaneous cardiac and sympathetic baroreflex sensitivity and perturbs BP regulation in healthy young humans. Heart rate (HR; electrocardiography), beat-to-beat BP (photoplethysmography), and muscle sympathetic activity (MSNA, microneurography) were continuously measured in 10 young subjects (4 females) during rest across two randomized experimental visits: 1) after 3 h of oral administration of placebo (PLA, 10 mg of methylcellulose within a gelatin capsule) and 2) after 3 h of oral administration of AMD (10 mg). Visits were separated for at least 48 h. We calculated the standard deviation and other indices of BP variability. Spontaneous cardiac baroreflex was assessed via the sequence technique and cardiac autonomic modulation through time- and frequency-domain HR variability. The sensitivity (gain) of the sympathetic baroreflex was determined via weighted linear regression analysis between MSNA and diastolic BP. AMD did not affect HR, BP, and MSNA compared with PLA. Indexes of cardiac autonomic modulation (time- and frequency-domain HR variability) and BP variability were also unchanged after AMD ingestion. Likewise, AMD did not modify the gain of both spontaneous cardiac and sympathetic arterial baroreflex. A single oral dose of AMD does not affect spontaneous arterial baroreflex sensitivity and BP variability in healthy young adults. NEW & NOTEWORTHY: Preclinical models indicate that amiloride (AMD), a nonselective antagonist of the acid-sensing ion channels (ASICs), impairs baroreflex sensitivity and perturbs blood pressure regulation. We translated these findings into humans, investigating the impact of acute oral ingestion of AMD on blood pressure variability and spontaneous cardiac and sympathetic baroreflex sensitivity in healthy young humans. In contrast to preclinical evidence, AMD does not impair spontaneous arterial baroreflex sensitivity and blood pressure variability in healthy young adults. [ABSTRACT FROM AUTHOR]

The venous distension reflex (VDR) is a pressor response evoked by peripheral venous distension and accompanied by increased muscle sympathetic nerve activity (MSNA). The effects of venous distension on the baroreflex, an important modulator of blood pressure (BP), have not been examined. The purpose of this study was to examine the effect of the VDR on baroreflex sensitivity (BRS). We hypothesized that the VDR will increase the sympathetic BRS (SBRS). Beat-by-beat heart rate (HR), BP, and MSNA were recorded in 16 female and 19 male young healthy subjects. To induce venous distension, normal saline equivalent to 5% of the forearm volume was infused into the veins of the occluded forearm. SBRS was assessed from the relationship between diastolic BP and MSNA during spontaneous BP variations. Cardiovagal BRS (CBRS) was assessed with the sequence technique. Venous distension evoked significant increases in BP and MSNA. Compared with baseline, during the maximal VDR response period, SBRS was significantly increased (-3.1 ± 1.5 to -4.5 ± 1.6 bursts·100 heartbeats-1·mmHg-1, P < 0.01) and CBRS was significantly decreased (16.6 ± 5.4 to 13.8 ± 6.1 ms·mmHg-1, P < 0.01). No sex differences were observed in the effect of the VDR on SBRS or CBRS. These results indicate that in addition to its pressor effect, the VDR altered both SBRS and CBRS. We speculate that these changes in baroreflex function contribute to the modulation of MSNA and BP during limb venous distension. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that oxidative stress plays an important role in peripheral artery disease (PAD). Prior reports suggested autonomic dysfunction in PAD. We hypothesized that responses of the autonomic nervous system and coronary tone would be impaired in patients with PAD during exposure to acute hyperoxia, an oxidative stressor. In 20 patients with PAD and 16 healthy, sex- and age-matched controls, beat-by-beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 min during room air breathing and 5 min of hyperoxia. Cardiovagal baroreflex sensitivity and HR variability (HRV) were evaluated as measures of autonomic function. Transthoracic coronary echocardiography was used to assess peak coronary blood flow velocity (CBV) in the left anterior descending coronary artery. Cardiovagal baroreflex sensitivity at rest was lower in PAD than in healthy controls. Hyperoxia raised BP solely in the patients with PAD, with no change observed in healthy controls. Hyperoxia induced an increase in cardiac parasympathetic activity assessed by the high-frequency component of HRV in healthy controls but not in PAD. Indices of parasympathetic activity were lower in PAD than in healthy controls throughout the trial as well as during hyperoxia. Hyperoxia induced coronary vasoconstriction in both groups, while the coronary perfusion time fraction was lower in PAD than in healthy controls. These results suggest that the response in parasympathetic activity to hyperoxia (i.e., oxidative stress) is blunted and the coronary perfusion time is shorter in patients with PAD. NEW & NOTEWORTHY: Patients with peripheral artery disease (PAD) showed consistently lower parasympathetic activity and blunted cardiovagal baroreflex sensitivity compared with healthy individuals. Notably, hyperoxia, which normally boosts parasympathetic activity in healthy individuals, failed to induce this response in patients with PAD. These data suggest altered autonomic responses during hyperoxia in PAD. [ABSTRACT FROM AUTHOR]

Prior reports show that whole body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole body heating (WBH; e.g., increase in internal temperature Tcore of ∼0.4°C–0.5°C) or limb heating on sympathetic and cardiovascular responses to exercise in older healthy humans remain unclear. We examined the muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP), and heart rate (HR) in 14 older (62 ± 2 yr) healthy subjects during fatiguing isometric handgrip exercise and postexercise circulatory occlusion (PECO). The protocol was performed under normothermic, moderate WBH, and local limb (i.e., forearm) heating conditions during three visits. During the mild WBH stage (increase in Tcore of <0.3°C), HR increased, whereas BP and MSNA decreased from baseline. Under the moderate WBH condition (increase in Tcore of ∼0.4°C), BP decreased, HR increased, and MSNA was unchanged from baseline. Compared with the normothermic trial, the absolute MAP during fatiguing exercise and PECO was lower during the WBH trial. Moreover, MSNA and MAP responses (i.e., changes) to fatiguing exercise were also less than those seen during the normothermic trial. Limb heating induced a similar increase in forearm muscle temperature to that seen in the WBH trial (∼0.7°C–1.5°C). Limb heating did not alter resting MAP, HR, or MSNA. The MSNA and hemodynamic responses to exercise in the limb heating trial were not different from those in the normothermic trial. These data suggest that moderate WBH attenuates MSNA and BP responses to exercise in older healthy humans. [ABSTRACT FROM AUTHOR]

Autonomic dysfunction is a common complication of type 2 diabetes mellitus (T2DM). However, the character of dysfunction varies in different reports. Differences in measurement methodology and complications might have influenced the inconsistent results. We sought to evaluate comprehensively the relationship between abnormal glucose metabolism and autonomic function at rest and the response to exercise in healthy individuals and T2DM patients. We hypothesized that both sympathetic and parasympathetic indices would decrease with the progression of abnormal glucose metabolism in individuals with few complications related to high sympathetic tone. Twenty healthy individuals and 11 T2DM patients without clinically evident cardiovascular disease other than controlled hypertension were examined. Resting muscle sympathetic nerve activity (MSNA), heart rate variability, spontaneous cardiovagal baroreflex sensitivity (CBRS), sympathetic baroreflex sensitivity and the MSNA response to handgrip exercise were measured. Resting MSNA was lower in patients with T2DM than in healthy control subjects (P = 0.011). Resting MSNA was negatively correlated with haemoglobin A1c in all subjects (R = −0.45, P = 0.024). The parasympathetic components of heart rate variability and CBRS were negatively correlated with glycaemic/insulin indices in all subjects and even in the control group only (all, P < 0.05). In all subjects, the MSNA response to exercise was positively correlated with fasting blood glucose (R = 0.69, P < 0.001). Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters throughout diabetic and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in T2DM. What is the central question of this study?Are sympathetic and parasympathetic nerves at rest and during exercise equally impaired in type 2 diabetes mellitus? What is the relationship of these dysfunctions to abnormal glucose metabolism?What is the main finding and its importance?Resting sympathetic activity and parasympathetic modulation of heart rate were decreased in relationship to abnormal glucose metabolism. Meanwhile, the sympathetic responses to handgrip were preserved in diabetics. The responses were correlated with glucose/insulin parameters in diabetics and control subjects. These results suggest the importance of a comprehensive assessment of autonomic function in diabetics. [ABSTRACT FROM AUTHOR]

Radiofrequency catheter ablation (RFCA) is a frequently performed procedure in patients with atrial fibrillation. Prior studies have shown that the RFCA may directly stimulate vagal afferents during the procedure, whereas the vagal tone assessed by heart rate variability (HRV) is lowered weeks after the RFCA procedure. The effects of RFCA performed in the left atrium on sympathetic nerve activity have not been assessed. In the present study, we hypothesized that RFCA would lower muscle sympathetic nerve activity (MSNA) during ablation and would raise MSNA 1 day postablation. A total of 18 patients were studied. In protocol 1 (n=10), electrocardiogram, blood pressure, and MSNA in the peroneal nerve were recorded through the RFCA procedure performed in the electrophysiology laboratory. In protocol 2, eight patients were studied before the procedure and 1 day postablation. RFCA led to a decrease in MSNA immediately after the procedure (25.4 ± 3.2 to 17.2 ± 3.8 bursts/min, P < 0.05). Cardiac parasympathetic activity was determined using indexes of HRV and increased during the procedure. One day postablation, MSNA was above baseline values (21.3 ± 3.7 to 35.7 ± 2.6 bursts/min, P < 0.05). HRV indexes of cardiac parasympathetic activity fell, and the HRV index of sympathovagal balance was not significantly altered. The results show that RFCA raised cardiac parasympathetic activity and decreased MSNA during the procedure. One day postablation, MSNA rose and cardiac parasympathetic activity fell. In addition, RFCA evokes differentiated sympathetic responses directed to the heart and skeletal muscles. [ABSTRACT FROM AUTHOR]

Peripheral artery disease (PAD) refers to obstructed blood flow in peripheral arteries typically due to atherosclerotic plaques. How PAD alters aortic blood pressure and pressure wave propagation during exercise is unclear. Thus, this study examined central blood pressure responses to plantar flexion exercise by investigating aortic pulse wave properties in PAD. Thirteen subjects with PAD and 13 healthy [age-, sex-, body mass index (BMI) matched] subjects performed rhythmic plantar flexion for 14 min or until fatigue (20 contractions/min; started at 2 kg with 1 kg/min increment up to 12 kg). Brachial (oscillometric cuff) and radial (SphygmoCor) blood pressure and derived-aortic waveforms were analyzed during supine rest and plantar flexion exercise. At rest, baseline augmentation index (P ¼ 0.0263) and cardiac wasted energy (P ¼ 0.0321) were greater in PAD due to earlier arrival of the reflected wave (P ¼ 0.0289). During exercise, aortic blood pressure (aMAP) and aortic pulse pressure showed significant interaction effects (P ¼ 0.0041 and P ¼ 0.0109, respectively). In particular, PAD had a greater aMAP increase at peak exercise (P ¼ 0.0147). Moreover, the tension time index was greater during exercise in PAD (P ¼ 0.0173), especially at peak exercise (P ¼ 0.0173), whereas the diastolic time index (P ¼ 0.0685) was not different between the two groups. Hence, during exercise, the subendocardial viability ratio was lower in PAD (P ¼ 0.0164), especially at peak exercise (P ¼ 0.0164). The results suggest that in PAD, the aortic blood pressure responses and myocardial oxygen demand during exercise are increased compared with healthy controls. [ABSTRACT FROM AUTHOR]

Heat stress evokes significant increases in muscle sympathetic nerve activity (MSNA) in healthy individuals. The MSNA response to heat stress in chronic heart failure (CHF) is unknown. We hypothesized that the MSNA response to heat stress is attenuated in CHF. Passive whole body heating was applied with water-perfused suits in 13 patients (61 ± 2 yr) with stable class II-III CHF, 12 age-matched (62 ± 2 yr) healthy subjects, and 14 young (24 ± 1 yr) healthy subjects. Mild heating (i.e., increases in skin temperature ΔTsk ~2-4°C, internal temperature ΔTcore <0.3°C) significantly decreased MSNA in CHF patients; however, it did not significantly alter the MSNA in the age-matched and young healthy subjects. Heat stress (i.e., ΔTsk ~4°C and ΔTcore ~0.6°C) raised MSNA in the age-matched (32.9 ± 3.2 to 45.6 ± 4.2 bursts/min; P < 0.001) and young (14.3 ± 1.7 to 26.3 ± 2.4 bursts/min; P < 0.001) controls, but not in CHF (46.2 ± 5.3 to 50.5 ± 5.3 bursts/min; P = 0.06). The MSNA increase by the heat stress in CHF (Δ4.2 ± 2.0 bursts/min) was significantly less than those seen in the age-matched (Δ12.8 ± 1.7 bursts/min, P < 0.05) and young (Δ12.0 ± 2.7 bursts/min, P < 0.05) control groups. These data suggest that the MSNA response to heat stress is attenuated in CHF patients. We speculate that the attenuated MSNA response to heat stress may contribute to impaired cardiovascular adjustments in CHF in a hot environment. [ABSTRACT FROM AUTHOR]

Renal sympathetic nerve activation is essential for the development of stress-induced hypertension. High dietary salt (HDS) also contributes to the development of some forms of hypertension. However, it is unclear whether HDS modulates sympathetically mediated renal vascular resistance (RVR) responses during physiological stress in humans. We hypothesized that renal vasoconstrictor responses during stress would be enhanced with HDS. Beat-by-beat measurements of renal blood flow velocity (RBV), blood pressure (BP) and heart rate were obtained in nine normotensive subjects during graded static handgrip (HG) and lower body negative pressure (LBNP) protocols before and after 7 days of HDS. RVR index was calculated by dividing mean BP by RBV. Baseline hemodynamics and plasma norepinephrine were unchanged whereas epinephrine was increased (P < .01) with HDS. In contrast to our hypothesis, increases in RVR during 15 s HG at 70% maximum voluntary contraction were less (P < .04) in the subjects who showed a "large" reduction (>70%) in PRA after HDS. Importantly, the magnitude of this attenuation correlated directly to the drop in PRA after HDS (r = .84; P < .02). RVR responses were also less within the same subjects during LBNP at -10 mmHg after HDS (P < .02) although the responses were similar at -30 and -50 mmHg. In conclusion, HDS attenuates the RVR responses during high intensity handgrip especially in subjects with a large reduction in PRA. We speculate that diminished renin-angiotensin system after HDS led to enhanced arterial baroreflex restraint of the muscle mechanoreflex induced renal vasoconstriction during exercise. [ABSTRACT FROM AUTHOR]

Sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) influences on cardiac rhythm at the onset of exercise, a time of rapid autonomic adjustments, are clinically important areas of investigation. Continuous wavelet transform (CWT) involves time‐frequency‐based heart rate variability (HRV) analysis allowing investigation of autonomic influences on cardiac rhythm during short durations of exercise. Therefore, the purpose of this study was to characterize SNS and PNS influences on cardiac rhythm at the onset of isometric exercise in healthy young adults. CWT analysis was retrospectively applied to R‐R interval data (electrocardiogram) previously collected from 14 healthy young adults (26 ± 2 years) who performed 30‐s, one‐legged, isometric, calf exercise at 70% maximal voluntary contraction (MVC; 70% MVC trial) or rested (0% MVC trial). Absolute and normalized low‐frequency (aLF, nLF; 0.04–0.15 Hz) and high‐frequency (aHF, nHF; 0.15–0.4 Hz) bands and LF/HF were used to analyze one 30‐s baseline period and six 5‐s time windows during the 30‐s exercise (70% MVC) or rest (0% MVC). Statistical analysis involved two‐way analysis of variance with post‐hoc analysis. aHF, aLF, LF/HF, nHF, and nLF displayed a trial‐time interaction (all p ≤ 0.027). In the 70% compared to the 0% MVC trial, aHF and nHF were lower after 5–30 s (all p ≤ 0.040), aLF was lower after 20–30 s (all p ≤ 0.011) and LF/HF and nLF were higher after 5–20 s (all p ≤ 0.045). These results indicate the reduction of the PNS influence on cardiac rhythm begins sooner than the augmentation of the SNS influence at the onset of isometric exercise in healthy young adults. [ABSTRACT FROM AUTHOR]

Amiloride has been shown to inhibit acid-sensing ion channels (ASICs), which contribute to ischemia-related muscle pain during exercise. The purpose of this study was to determine if a single oral dose of amiloride would improve exercise tolerance and attenuate blood pressure during blood-flow-restricted (BFR) exercise in healthy adults. Ten subjects (4 females) performed isometric plantar flexion exercise with BFR (30% maximal voluntary contraction) after ingesting either a 10-mg dose of amiloride or a volume-matched placebo (random order). Time to failure, time-tension index (TTI), and perceived pain (visual analog scale) were compared between the amiloride and placebo trials. Mean blood pressure, heart rate, blood pressure index (BPI), and BPI normalized to TTI (BPInorm) were also compared between trials using both time-matched (TM50 and TM100) and effort-matched (T50 and T100) comparisons. Time to failure (+69.4 ± 63.2 s, P < 0.01) and TTI (+1,441 ± 633 kg·s, P = 0.02) were both significantly increased in the amiloride trial compared with placebo, despite no increase in pain (+0.4 ± 1.7 cm, P = 0.46). In contrast, amiloride had no significant influence on the mean blood pressure or heart rate responses, nor were there any significant differences in BPI or BPInorm between trials when matched for time (all P ≥ 0.13). When matched for effort, BPI was significantly greater in the amiloride trial (+5,300 ± 1,798 mmHg·s, P = 0.01), likely owing to an increase in total exercise duration. In conclusion, a 10-mg oral dose of amiloride appears to significantly improve the tolerance to BFR exercise in healthy adults without influencing blood pressure responses. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Increased central arterial stiffness and enhanced arterial wave reflections may contribute to increased risk of cardiovascular disease development with advancing age. Omega-3 polyunsaturated fatty acid ( n-3) ingestion may reduce cardiovascular risk via favorable effects exerted on arterial structure and function. We determined the effects of n-3 supplementation (4 g/day for 12 weeks) on important measures of central arterial stiffness (carotid-femoral pulse wave velocity; PWV) and arterial wave reflection (central augmentation index) in young ( n = 12; 25 ± 1-year-old, mean ± SE) and older ( n = 12; 66 ± 2) healthy adults. We hypothesized that n-3 supplementation would decrease carotid-femoral PWV and central augmentation index in older adults. Our results indicate that carotid-femoral PWV and central augmentation index were greater in older (988 ± 65 cm/sec and 33 ± 2%) than in young adults (656 ± 16 cm/sec and 3 ± 4%: both P < 0.05 compared to older) before the intervention (Pre). N-3 supplementation decreased carotid-femoral PWV in older (∆-9 ± 2% Precompared to Post; P < 0.05), but not young adults (∆2 ± 3%). Central augmentation index was unchanged by n-3 supplementation in young (3 ± 4 vs. 0 ± 4% for Pre and Post, respectively) and older adults (33 ± 2 vs. 35 ± 3%). Arterial blood pressure at rest, although increased with age, was not altered by n-3 supplementation in young or older adults. Collectively, these data indicate that 12 weeks of daily n-3 supplementation decreases an important measure of central arterial stiffness (carotid-femoral PWV) in older, but not young healthy adults. The mechanism underlying decreased central arterial stiffness with n-3 supplementation is unknown, but appears to be independent of effects on arterial blood pressure or arterial wave reflections. [ABSTRACT FROM AUTHOR]

Classic canine studies suggest that central great vein distension evokes an autonomic reflex tachycardia (Bainbridge reflex). It is unclear whether central venous distension in humans is a necessary and sufficient stimulus to evoke a reflex increase in heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA). Prior work from our laboratory suggests that limb venous distension evokes a reflex increase in BP and MSNA in humans. We hypothesized that in humans, compared with the limb venous distension, inferior vena cava (IVC) distension would evoke a less prominent increase in HR and MSNA. IVC distension (monitored with ultrasonography) was induced by two methods: 1) head-down tilt (HDT, N ＝ 13); and 2) lower-body positive pressure (LBPP, N ＝ 10). Two minutes of HDT induced IVC distension (Δ2.6 ± 0.2 mm, P ＜ 0.001, ~27% in cross-sectional area), slightly increased mean BP (Δ2.3 ± 0.7 mmHg, P ＝ 0.005), decreased MSNA (Δ5.2 ± 0.8 bursts/min, P ＜ 0.001, N ＝ 10), and did not alter HR (P ＝ 0.37). LBPP induced similar IVC distension, increased BP (Δ2.0 ± 0.7 mmHg, P ＜ 0.01), and did not alter HR (P ＝ 0.34). Thus central venous distension leads to a rapid increase in BP and a subsequent fall in MSNA. Central venous distension does not evoke either bradycardia or tachycardia in humans. The absence of a baroreflex-mediated bradycardia suggests that the Bainbridge reflex is engaged. Clearly, this reflex differs from the powerful sympathoexcitation peripheral venous distension reflex described in humans. [ABSTRACT FROM AUTHOR]

Key points Peripheral arterial disease (PAD) is a common and debilitating condition linked with heightened risk of cardiovascular mortality., Dynamic exercise elicits augmented blood pressure responses in PAD that could put the patient at risk for adverse event but the underlying mechanisms are unknown., The exercise pressor reflex is comprised of group III and group IV muscle afferents that increase their discharge in response to mechanical and/or chemical stimulation., In this study, we demonstrate that mechanically sensitive muscle afferents cause augmented reflex elevations in blood pressure during dynamic plantar flexion exercise in PAD. These responses occur prior to claudication pain, are related to disease severity and can be partly reduced by acute antioxidant infusion., Abstract Exaggerated blood pressure (BP) responses to dynamic exercise predict cardiovascular mortality in patients with peripheral arterial disease (PAD). However, the underlying mechanisms are unclear and no attempt has been made to attenuate this response using antioxidants. Three physiological studies were conducted in patients with PAD and controls. In Protocol 1, subjects underwent 4 min of low-intensity (0.5-2.0 kg), rhythmic plantar flexion in the supine posture. In Protocol 2, patients with PAD received high-dose ascorbic acid intravenously before exercise. In Protocol 3, involuntary exercise was conducted via electrical stimulation of the tibial nerve. The primary outcome measure was Δ mean arterial pressure (MAP) during the first 20 s of exercise (i.e. the onset of sympathoexcitation by muscle afferents). Compared to controls, patients with PAD had significantly greater ΔMAP during plantar flexion, particularly at 0.5 kg with the most affected leg (11 ± 2 vs. 2 ± 1 mmHg) as well as the least affected leg (7 ± 1 vs. 1 ± 1 mmHg). This augmented response occurred before the onset of claudication pain and was attenuated by ∼50% with ascorbic acid. Electrically evoked exercise also elicited larger haemodynamic changes in patients with PAD compared to controls. Further, the ΔMAP during 0.5 kg plantar flexion inversely correlated with the ankle-brachial index, indicating that patients with more severe resting limb ischaemia have a larger BP response to exercise. The BP response to low-intensity exercise was enhanced in PAD. Chronic limb ischaemia may sensitize muscle afferents and potentiate the BP response to muscle contraction in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

We have recently shown that a saline infusion in the veins of an arterially occluded human forearm evokes a systemic response with increases in muscle sympathetic nerve activity (MSNA) and blood pressure. In this report, we examined whether this response was a reflex that was due to venous distension. Blood pressure (Finometer), heart rate, and MSNA (microneurography) were assessed in 14 young healthy subjects. In the saline trial (n = 14), 5% forearm volume normal saline was infused in an arterially occluded arm. To block afferents in the limb, 90 mg of lidocaine were added to the same volume of saline in six subjects during a separate visit. To examine whether interstitial perfusion of normal saline alone induced the responses, the same volume of albumin solution (5% concentration) was infused in 11 subjects in separate studies. Lidocaine abolished the MSNA and blood pressure responses seen with saline infusion. Moreover, compared with the saline infusion, an albumin infusion induced a larger (MSNA: Δ14.3 ± 2.7 vs. Δ8.5 ± 1.3 bursts/min, P < 0.01) and more sustained MSNA and blood pressure responses. These data suggest that venous distension activates afferent nerves and evokes a powerful systemic sympathoexcitatory reflex. We posit that the venous distension plays an important role in evoking the autonomic adjustments seen with postural stress in human subjects. [ABSTRACT FROM AUTHOR]

During exercise, sympathetic nervous system activity increases and this contributes to an increase in blood pressure (i.e. exercise pressor reflex). Although animal studies suggest that purinergic P2 receptors on thin fibre sensory nerves are stimulated and evoke this reflex, human data are lacking. In this study, young healthy volunteers performed fatiguing isometric handgrip before and after a local infusion of pyridoxine (i.e. vitamin B) into the 'isolated' circulation of the human forearm. Pyridoxine is converted into a P2-purinoceptor antagonist. Muscle sympathetic nerve activity and blood pressure responses to fatiguing handgrip and post-exercise circulatory occlusion were significantly less after pyridoxine than they were before. These effects were not observed after infusion of saline. These data suggest that P2 receptors contribute to the exercise pressor reflex in humans. [ABSTRACT FROM AUTHOR]

The role adenosine plays in evoking the exercise pressor reflex in humans remains controversial. We hypothesized that localized forearm adenosine receptor blockade would attenuate muscle sympathetic nerve activity (MSNA) responses to fatiguing handgrip exercise in humans. Blood pressure (Finometer), heart rate, and MSNA from the peroneal nerve were assessed in 11 healthy young volunteers during fatiguing isometric handgrip, postexercise circulatory occlusion (PECO), and passive muscle stretch during PECO. The protocol was performed before and after adenosine receptor blockade by local infusion of 40 mg aminophylline in saline via forearm Bier block (regional intravenous dnesthesia). In the second experiment, the same amount of saline was infused via the Bier block. After aminophylline, the MSNA and blood pressure responses to fatiguing handgrip, PECO, and passive stretch (all P < 0.05) were significantly greater than during the control condition. Saline Bier block had no similar effects on the MSNA and blood pressure responses. These data suggest that adenosine receptor antagonism in the exercising muscles may accentuate sympathetic activation during fatiguing exercise. [ABSTRACT FROM AUTHOR]

The aim of this investigation was to determine the acute effects of isometric fatiguing handgrip (IFHG) and lower body negative pressure (LBNP) on indices of central arterial stiffness. Thirteen subjects were studied. Renal blood velocity (Duplex Ultrasound) and blood pressure (Finapres) were monitored during IFHG and LBNP at -30 and -50 mmHg. Radial pulse-wave forms were recorded by applanation tonometry. Central aortic waveforms and other hemodynamic parameters were assessed using the Sphygmocor software. Renal vascular resistance index (RVRI; mean BP/renal blood velocity) was used as index of sympathetic nervous system (SNS) engagement. RVRI increased during both IFHG and LBNP indicating that SNS was engaged; however, BP increased only during the IFHG. Pulse-wave analysis showed that during the IFHG protocol the transit time of the pulse wave decreased and the peripheral pulse pressure/nonaugmented central pulse pressure ratio increased from baseline. Both of these measurements suggest an increase in central large artery stiffness. During LBNP no changes in the indices of central stiffness were noted, in spite of a similar level of sympathetic system engagement. Heart rate increased during both protocols, whereas augmentation index increased during the IFHG protocol and decreased during the LBNP. Our major conclusion was that blood pressure rather than sympathetic activity seems to play the major role in modulating the elastic properties of the central arteries. The decrease in augmentation index during the LBNP protocol can be attributed to the increased heart rate, given that there is a negative correlation between these two parameters. [ABSTRACT FROM AUTHOR]

Renal circulatory adjustments to stress contribute to blood pressure and volume regulation. Both handgrip (HG) and disengagement of baroreflexes with lower body negative pressure (LBNP) can engage the sympathetic nervous system (SNS). However, the effect of simultaneous HG and LBNP on the renal circulation in humans is not known. Eighteen young healthy volunteers were studied. Beat-to-beat changes in renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres) and heart rate (ECG) were monitored during (a) 15 s HG at 30% maximum voluntary contraction (MVC); (b) LBNP at −10 and −30 mmHg (each level for 5 min); and (c) 15 s HG (at 30% MVC) during LBNP at both levels. Renal vascular resistance index (RVR units) was calculated by dividing MAP by RBV. The increases in RVR during HG alone (12 ± 6%) were not different from the responses noted during combined HG and LBNP (17 ± 6% at −10 mmHg and 25 ± 8% at −30 mmHg). These results suggest occlusion occurs between a neural circuit engaged during 15 s of HG (central command and/or the muscle mechanoreflex) and a circuit activated by LBNP. In additional experiments ( n= 6), similar non-algebraic summation of RVR was seen during 15 s involuntary biceps contractions (engages only muscle reflexes) and LBNP. With respect to RVR, neural occlusion occurs between baroreflexes and the muscle mechanoreflex. Muscle mechanoreflex mediated renal vasoconstriction during short bouts of HG is not influenced by baroreflex disengagement. [ABSTRACT FROM AUTHOR]

Purpose: Although it is known that peripheral arterial disease (PAD) is associated with chronic myopathies, the acute muscular responses to exercise in this population are less clear. This study used diffusion tensor imaging (DTI) to compare acute exercise-related muscle damage between PAD patients and healthy controls. Methods: Eight PAD patients and seven healthy controls performed graded plantar flexion in the bore of a 3T MRI scanner. Exercise began at 2 kg and increased by 2 kg every 2 min until failure, or completion of 10 min of exercise. DTI images were acquired from the lower leg pre- and post-exercise, and were analyzed for mean diffusivity, fractional anisotropy (FA), and eigenvalues 1–3 (λ1–3) of the medial gastrocnemius (MG) and tibialis anterior (TA). Results: Results indicated a significant leg by time interaction for mean diffusivity, explained by a significantly greater increase in diffusivity of the MG in the most affected legs of PAD patients (11.1 × 10–4 ± 0.5 × 10–4 mm2/s vs. 12.7 × 10–4 ± 1.2 × 10–4 mm2/s at pre and post, respectively, P = 0.02) compared to healthy control subjects (10.8 × 10–4 ± 0.3 × 10–4 mm2/s vs. 11.2 × 10–4 ± 0.5 × 10–4 mm2/s at pre and post, respectively, P = 1.0). No significant differences were observed for the TA, or λ1–3 (all P ≥ 0.06). Moreover, no reciprocal changes were observed for FA in either group (all P ≥ 0.29). Conclusion: These data suggest that calf muscle diffusivity increases more in PAD patients compared to controls after exercise. These findings are consistent with the notion that acute exercise results in increased muscle damage in PAD. [ABSTRACT FROM AUTHOR]

R1727 --> Prior reports show that whole‐body heat stress attenuates the pressor response to exercise in young healthy subjects. The effects of moderate whole‐body heating (WBH, e.g. increase in internal temperature Tcore ~0.4‐0.5 °C) on sympathetic and cardiovascular responses to exercise in older healthy humans remains unclear. We examined muscle sympathetic nerve activity (MSNA), mean arterial blood pressure (MAP) and heart rate (HR) in 14 older (62 ± 7 yrs. mean ± SD) healthy subjects during fatiguing isometric handgrip exercise and post exercise circulatory occlusion (PECO). The protocol was performed under normothermic and moderate WBH conditions during 2 visits. Under the moderate WBH condition (ΔTcore ~0.4 ± 0.1 °C), MAP decreased (90.0 ± 6.6 to 86.4 ± 7.1 mmHg), HR increased (60.8 ± 7.9 to 71.7 ± 9.7 beats/min), while MSNA was unchanged (34.7 ± 9.2 to 37.5 ± 15.4 bursts/min) from the baseline before heating. Hemodynamic variables and MSNA did not change significantly during the time control period in the normothermic trial. Compared with the normothermic trial, the absolute MAP during fatiguing exercise (102.7 ± 8.5 vs. 117.2 ± 11.4 mmHg) and PECO (98.2 ± 8.9 vs. 113.9 ± 12.5 mmHg) were lower during the WBH trial. Moreover, MSNA (Δ8.4 ± 6.5 vs. Δ14.0 ± 7.2 bursts/min) and MAP (Δ16.5 ± 7.5 vs. Δ23.2 ± 8.2 mmHg) responses (i.e. changes) to fatiguing exercise were also less than those seen during the normothermic trial. These data suggest that moderate WBH attenuates reflex exercise pressor responses in older healthy humans. Further studies are needed to examine if WBH can attenuate exercise pressor responses in patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

R1755 --> Prior reports have shown that that venous distension induced by saline infusion into the veins of an arterially occluded forearm significantly raises muscle sympathetic nerve activity (MSNA) and blood pressure (BP) via activating afferent nerves in the forearm in healthy humans. Thus, peripheral venous distension induces a systemic sympatho‐excitatory reflex (venous distension reflex, VDR). The baroreflex is an important modulator of BP via regulating sympathetic and vagal tone. However, the relationship between the VDR and the baroreflex has not been examined. Thus, the purpose of this study was to examine the relationship between VDR and the cardiovagal baroreflex sensitivity (CBRS) or sympathetic baroreflex sensitivity (SBRS). We hypothesized that VDR activation affects the CBRS and SBRS. Beat‐to‐beat heart rate (HR), BP and MSNA were recorded in 35 (19 M, 16 F) young healthy subjects (27 ± 1 yrs.). After a short period when a forearm was arterially occluded, 5% forearm volume normal saline (~40‐60 ml) was infused into the veins of the occluded forearm at a rate of 30 ml/min. Prior studies showed that the maximal MSNA and BP responses occurred during the period of 30 seconds before and 30 seconds after the end of the saline infusion (maximal VDR responses). Thus, hemodynamic variables, MSNA, SBRS and CBRS were assessed during baseline (5 min) and the maximal VDR response period (1 min). SBRS was evaluated by analyzing the relationship between spontaneous variations in diastolic BP and MSNA. CBRS was assessed with the sequence technique. Mean BP, HR and MSNA during the maximal VDR response period were significantly greater than those during resting baseline (Baseline to VDR; MBP, 83.9 ± 1.8 to 98.6 ± 2.5 mmHg; HR, 65.2 ± 1.5 to 68.0 ± 1.9 bpm; MSNA, 22.8 ± 1.6 to 32.7 ± 1.7 bursts･min‐1; all P < 0.05). SBRS absolute value during VDR was significantly increased (‐0.66 ± 0.07 to ‐1.41 ± 0.10 units･beat‐1･mmHg‐1, P < 0.05) and SBRS operating point was reset and upward shifted. CBRS during VDR was significantly decreased (Baseline to VDR; 16.6 ± 0.9 to 13.8 ± 1.0 ms･mmHg‐1, P < 0.05). These results indicate that VDR activation increased SBRS with an upward shift of the operating point and decreased CBRS, as it also evoked significant sympatho‐excitation. Augmented sympathetic activity and impaired baroreflex function are important prognostic factors in patients with cardiovascular diseases. Thus, further studies are needed to examine VDR in patients with cardiovascular diseases. [ABSTRACT FROM AUTHOR]

R1729 --> Augmented sympathetic nerve activity (SNA) and impaired baroreflex sensitivity (BRS) are important therapeutic targets in patients with cardiovascular diseases. Nitroglycerin (glyceryl trinitrate, GTN) is a vasodilator, widely used in patients with coronary artery diseases, however, the effects of GTN on SNA and BRS are incompletely understood. Importantly, the acute effects of GTN on SNA and BRS are not clear. Additionally, there are no reports evaluating both the sympathetic BRS (SBRS) and cardiovagal BRS (CBRS) responses to the administration of sublingual GTN. The purpose of this study was to assess the acute effects of GTN on muscle sympathetic nerve activity (MSNA), SBRS and CBRS in healthy subjects. We hypothesized that sublingual GTN would rapidly modulate sympathetic and cardiovagal BRS and thus increase MSNA in healthy subjects. Ten (9M, 1F) healthy subjects (60 ± 2 yrs) without medications were examined. Beat‐to‐beat heart rate (HR), arterial pressure (AP) and MSNA were recorded before and for 10 min after sublingual administration of GTN 0.4 mg. SBRS was evaluated by analyzing the relationship between spontaneous variations in diastolic AP and MSNA. CBRS was assessed with the sequence technique. Every 2 min HR, AP and MSNA data were recorded and compared. SBRS and CBRS were assessed during baseline, and during min 3‐6 (Post A) and 7‐10 min (Post B) after GTN administration. Compared to baseline, mean AP did not significantly change during Post A (baseline, 98.5 ± 1.8 to 95.6 ± 2.3 mmHg, P = 0.423) but decreased during Post B (91.9 ± 2.2 mmHg, P < 0.05). MSNA increased significantly by min 2 after GTN and remained significantly elevated during both the Post A and Post B periods (31.2 ± 4.0 to 48.2 ± 4.4, and 47.5 ± 4.2; bursts/min, both P < 0.05). Compared to baseline, during the Post A and Post B periods CBRS decreased significantly (12.9 ± 1.6 to 7.1 ± 1.0, and 6.4 ± 0.6; ms･mmHg‐1, both P < 0.05), while SBRS increased significantly (0.8 ± 0.2 to 1.5 ± 0.2, and 1.8 ± 0.3; units･beat‐1･mmHg‐1, both P < 0.05). The SBRS operating point was also reset and shifted to upward during both the Post A and Post B periods. The results show that a clinical sublingual dose of GTN attenuated the CBRS and raised the SBRS with an upward shift of the operating point, resulting in augmented MSNA. Whether these acute changes in MSNA and BRS with GTN in the absence of changes in BP can evoke adverse sequelae in patients with atherosclerosis is unknown. These findings have never been reported before. These factors should be considered by clinicians as they use this agent. [ABSTRACT FROM AUTHOR]

R3565 --> Skeletal muscle oxygenation is a commonly reported variable in human physiology research, and is often assessed using near‐infrared spectroscopy (NIRS). In recent years, a novel magnetic resonance imaging (MRI) sequence, termed PIVOT (Perfusion, IntraVenous Oxygenation, and T2*) has been used to quantify skeletal muscle oxygenation during reactive hyperemia protocols. While the skeletal muscle oxygenation responses appear to be similar between investigations using the MRI PIVOT sequence and NIRS, the agreement between these two indices has yet to be explicitly reported. Purpose: The purpose of this study was to determine the level of agreement between MRI PIVOT and NIRS based assessments of the skeletal muscle oxygenation (SmO2) response to a reactive hyperemia protocol. Methods: Fifteen subjects (6 males, 25 ± 3 yrs, 170.8 ± 11.9 cm, 73.6 ± 11.3 kg, 24.8 ± 1.9 kg/m2) participated in a single laboratory visit, which was divided into two separate experiments. In one experiment, three consecutive reactive hyperemia protocols (2 min baseline, 5 min arterial occlusion, 5 min reactive hyperemia) were performed on the dominant leg, each separated by ~10 minutes of rest. Arterial occlusion was applied to the upper thigh with a pneumatic pressure cuff, and SmO2 was recorded from the medial gastrocnemius (MG) and tibalis anterior (TA) via NIRS. Next, subjects were transitioned to the MRI facility, where the experiment was repeated inside the bore of a 3T MRI scanner. In this experiment, SmO2 was collected using an adaptation of the MRI PIVOT sequence, and was represented as the intensity of the T2* signal. The order of experiments (MRI vs. NIRS) were counterbalanced between subjects, and the three reactive hyperemia trials within each experiment were averaged into a single response curve. From those response curves, a Pearson's correlation analysis was used to examine the linear relationship between the NIRS Tissue Saturation Index (TSI) response and the MRI T2* response during reactive hyperemia. Likewise, the areas under the curve (AUC; 2 min) for TSI and T2* were calculated for each subject and were compared between experiments using Bland‐Altman Plots. Linear Regression Analyses were also used to assess any potential measurement bias. Results: Pearson's correlation analyses indicated a significant and moderate relationship between the reactive hyperemic responses collected via NIRS and MRI (R=0.760, P<0.001 and R=0.537, P<0.001 for the MG and TA, respectively). Bland Altman plots demonstrated a strong agreement between the TSI and T2* AUC values (data fell within the 95% confidence interval limits), and linear regression analyses were non‐significant (b= ‐0.753, P=0.068 and b=0.089, P=0.75 for the MG and TA, respectively), indicating no significant measurement bias. Conclusions: These data suggest that there is a moderate level of agreement between the MRI PIVOT and NIRS based assessments of the SmO2 response to reactive hyperemia. [ABSTRACT FROM AUTHOR]

It is unclear if the exaggerated exercise pressor reflex observed in peripheral arterial disease (PAD) patients facilitates Oxygen (O2) transport during presymptomatic exercise. Accordingly, this study compared O2 transport between PAD patients and healthy controls during graded presymptomatic work. Seven PAD patients and seven healthy controls performed dynamic plantar flexion in the bore of a 3T MRI scanner. Perfusion, T2* (an index of relative tissue oxygenation), and SvO2 (a measure of venous oxygen saturation) were collected from the medial gastrocnemius (MG) during the final 10 seconds of each stage. Blood pressure was also collected during the final minute of each stage. As expected, the pressor response to presymptomatic work (4 kg) was exaggerated in PAD patients compared to controls (+14 mmHg ± 4 and +7 mmHg ± 2, P ≤ 0.034). When normalized to changes in free water content (S0), T2* was lower at 2 kg in PAD patients compared to controls (−0.91 Δms/ΔAU ± 0.3 and 0.57 Δms/ΔAU ± 0.3, P ≤ 0.008); followed by a greater increase in perfusion at 4 kg in the PAD group (+18.8 mL/min/100g ± 6.2 vs. −0.21 mL/min/100g ± 3.2 in PAD and controls, P ≤ 0.026). Lastly, SvO2 decreased at 4 kg in both groups (−13% ± 4 and −2% ± 4 in PAD and controls, P ≤ 0.049), suggesting an increase in O2 extraction in the PAD group. Based on these findings, O2 transport appears to be augmented during graded presymptomatic work in PAD patients, and this may be partially mediated by an exaggerated pressor response. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Patients with heart failure and sleep apnea have greater chemoreflex sensitivity, presumably due to intermittent hypoxia (IH), and this is predictive of mortality. We hypothesized that endurance training would attenuate the effect of IH on peripheral chemoreflex sensitivity in healthy humans. Fifteen young healthy subjects (9 female, 26 ± 1 yr) participated. Between visits, 11 subjects underwent 8 wk of endurance training that included running four times/wk at 80% predicted maximum heart rate and interval training, and four control subjects did not change activity. Chemoreflex sensitivity (the slope of ventilation responses to serial oxygen desaturations), blood pressure, heart rate, and muscle sympathetic nerve activity (MSNA) were assessed before and after 30 min of IH. Endurance training decreased resting systolic blood pressure (119 ± 3 to 113 ± 3 mmHg; P = 0.027) and heart rate (67 ± 3 to 61 ± 2 beats/min; P = 0.004) but did not alter respiratory parameters at rest (P > 0.2). Endurance training attenuated the IH-induced increase in chemoreflex sensitivity (pretraining: Δ 0.045 ± 0.026 vs. posttraining: Δ -0.028 ± 0.040 l·min-1.% O2 desaturation-1; P = 0.045). Furthermore, IH increased mean blood pressure and MSNA burst rate before training (P < 0.05), but IH did not alter these measures after training (P > 0.2). All measurements were similar in the control subjects at both visits (P > 0.05). Endurance training attenuates chemoreflex sensitization to IH, which may partially explain the beneficial effects of exercise training in patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

R4729 --> 890.7 --> Changes in sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) influences on cardiac rhythm during exercise can be reflected in time‐ and frequency‐based heart rate variability (HRV) analysis and differ depending on exercise intensity. However, the SNS and PNS contributions to cardiac rhythm at the onset of exercise has not been investigated due to the complexity of applying HRV analysis during short durations of exercise. Continuous wavelet transform (CWT) combines time‐ and frequency‐based analyses to allow autonomic influences on beat‐to‐beat fluctuations in R‐R intervals (RRI) to be captured in rapidly changing signals, such as at the onset of exercise. Therefore, the objective of this study was to characterize the rapid autonomic adjustments influencing cardiac rhythm at the onset of exercise in healthy young adults. This study was a secondary analysis of data previously collected from 14 healthy young adults (26 ± 2 years, 6 male/8 female) during two trials: a 5‐minute baseline followed by performance of isometric, right‐calf exercise at 70% maximal voluntary contraction (MVC) for 30 seconds (70% MVC) or continued rest (0% trial). Heart rate was continuously measured using a three‐lead electrocardiogram from which RRIs were derived. Analysis involved applying CWT to the RRI data using low‐frequency (LF; 0.04‐0.15 Hz) and high‐frequency (HF; 0.15‐0.4 Hz) bands for HRV analysis. Log‐transformed absolute (aLF, aHF) and normalized (nLF, nHF) LF and HF time‐frequency bands and their ratio (LF/HF) were calculated for each time period (one baseline time period – 0‐30 seconds, and six rest/exercise time periods – 300‐305, 305‐310, 310‐315, 315‐320, 320‐325, and 325‐330 seconds) in each trial (0% and 70% MVC). Group means and standard deviations for all five variables were calculated for each time period in each trial. Statistical analysis involved two‐way repeated measures analysis of variance with post hoc analysis involving paired t tests and a Holm‐Bonferroni correction with statistical significance set at P < 0.05. It was hypothesized that the SNS influence on cardiac rhythm, measured by LF and LF/HF, would increase while the PNS influence on cardiac rhythm, measured by HF, would decrease at the onset of exercise in healthy young adults. There was a significant trial‐time interaction for aHF, aLF, and LF/HF (P < 0.001, P = 0.003, and P = 0.027, respectively). aHF was lower during 5‐30 seconds (all P ≤ 0.025), aLF was lower during 20‐30 seconds (all P ≤ 0.011), and LF/HF was higher during 5‐20 seconds (all P ≤ 0.045) following the start of exercise in the 70% MVC trial compared to the 0% trial. There were significant effects of trial for aHF, nLF, nHF, and LF/HF (all P ≤ 0.014) and time for aHF and LF/HF (all P ≤ 0.011). These results indicate that the reduction of the PNS influence on cardiac rhythm begins sooner than the augmentation of the SNS influence on cardiac rhythm at the onset of exercise in healthy young adults. [ABSTRACT FROM AUTHOR]

R859 --> 607.1 --> Prior reports suggest that oxidative stress plays an important role in the development of atherosclerotic diseases such as peripheral artery disease (PAD). The effects of acute hyperoxia, an important acute oxidative stressor, on autonomic function have not been well studied in PAD. We hypothesized that the autonomic responses to acute hyperoxia would be impaired in PAD. We studied 17 patients with PAD (12M, 5F, 67 ± 2 yrs) and 15 healthy controls (10M, 5F, 65 ± 2 yrs). The ankle‐brachial indexes in the patients were 0.57 ± 0.03 in the most affected leg and 0.77 ± 0.04 in the less affected leg, respectively. Beat‐by‐beat heart rate (HR, from ECG) and blood pressure (BP, with Finometer) were recorded for 10 min under normoxic resting conditions and during 5‐min hyperoxia (100% oxygen) as an acute oxidative stress test. HR variability (HRV) was calculated and cardiac baroreflex sensitivity (BRS) was estimated with the sequence technique. Under resting conditions, mean HR and mean arterial pressure (MAP) were not significantly different between the groups. Resting values of the root mean square of successive differences between normal heartbeats (RMSSD, a HRV index for parasympathetic activity; 14.1 ± 1.0 vs. 19.8 ± 2.2 ms, P = 0.032) and cardiac BRS (6.43 ± 0.78 vs. 14.86 ± 2.56 ms/mmHg, P = 0.001) were significantly lower in PAD than in healthy controls. Hyperoxia lowered HR in both groups and raised MAP only in patients with PAD. During hyperoxia both HR and MAP were significantly higher in PAD than in controls. Hyperoxia induced an increase in RMSSD and the high frequency (HF) component of HRV (another index for parasympathetic activity) in healthy subjects. However, during hyperoxia no increase in parasympathetic activity was observed in PAD. Both RMSSD and the HF component of the whole trial (i.e. baseline and hyperoxia) in PAD were lower than those in healthy control subjects. Hyperoxia did not induce changes in cardiac BRS in either group, while cardiac BRS of the whole trial in PAD was lower than that in healthy controls. These data suggest that resting parasympathetic activity and cardiac baroreflex function are impaired in PAD. Moreover, the autonomic response to acute oxidative stress (i.e. an increase in parasympathetic activity) is also impaired in PAD. Further studies are needed to examine if antioxidant agents can improve autonomic function in PAD. [ABSTRACT FROM AUTHOR]

R867 --> 748.1 --> Autonomic neuropathy is a common complication in diabetes mellitus (DM). Decreased vagal nerve activity and augmented sympathetic nerve activity have been reported in patients with DM. However, the relationship between autonomic function and glycemic status in DM and in individuals without DM remains unclear. We hypothesized that indices of sympathetic and vagal nerve activity are related to glycemic status. Eleven patients who were clinically diagnosed with type‐2 DM (HbA1c, 6.8 ± 0.3%; age, 54 ± 3 yrs), and 20 healthy non‐DM individuals (including 10 pre‐DM; HbA1c < 6.5%; range 5.1‐6.1%; age, 59 ± 2 yrs) were studied (19 male, 12 female). Five DM patients had hypertension. Patients with DM and hypertensives were treated with standard medications. Beat‐by‐beat blood pressure (BP), heart rate (HR) and muscle sympathetic nerve activity (MSNA) were recorded under resting conditions. HR variability (HRV) was calculated and spontaneous cardiovagal baroreflex sensitivity (CBRS) was evaluated with the sequence method. CBRS in DM was lower than in non‐DM subjects (P < 0.05). MSNA in DM was also lower than in non‐DM subjects (P < 0.05). In linear regression analyses with data from all subjects, CBRS was negatively correlated with fasting blood glucose (FBG) (R = ‐0.47), insulin (R = ‐0.42), and homeostasis model assessment of insulin resistance (HOMA‐IR) (R = ‐0.43) (P < 0.05 for all). MSNA was negatively correlated with HbA1c and HOMA‐IR (R = ‐0.41, ‐0.42, respectively; both, P < 0.05). The high frequency (HF) component of HRV (i.e., an index of vagal tone) was negatively correlated with insulin (R = ‐0.46) and HOMA‐IR (R = ‐0.42) in all subjects (P < 0.05 for both). In non‐DM subjects, CBRS was negatively correlated with FBG (R = ‐0.53, P <0.05). HF was negatively correlated with FBG (R = ‐0.51), insulin (R = ‐0.66), and HOMA‐IR (R = ‐0.66) (P < 0.05 for all), but MSNA was not correlated with glycemic/insulin status in non‐DM subjects. Whereas in DM patients, MSNA tended to be negatively correlated with HOMA‐IR (R = ‐0.77, P = 0.07). In the present study, both MSNA and vagal activity (CBRS and HF) were decreased in relation to the glycemic/insulin status. Vagal nerve activity was associated with the glycemic/insulin status even in non‐DM subjects (i.e., healthy and pre‐DM). Based on these results, we speculate that both vagal and sympathetic nerves were injured by DM progression, and that vagal neuropathy preceded the sympathetic neuropathy. Our results differ from prior reports that showed that MSNA in DM was higher than in non‐DM. However, in our study subjects, the severity of DM was mild, and except for hypertension in 5 subjects, none had manifestations of diabetic end‐organ damage. Differences in the duration and severity of DM as well as the effects of the treatments could contribute to the differences in the results. Further studies on the autonomic function during the DM progression are warranted. [ABSTRACT FROM AUTHOR]

R2276 --> 556.6 --> It has been almost two years since the Covid‐19 pandemic hit, with over 5 million deaths globally. It is known that endothelial activation and dysfunction play a crucial role in Covid‐19 pathogenesis. Evidence of widespread endothelial injury is found in advanced cases of Covid‐19, especially in people with cardiovascular comorbidities. However, the effects of Covid‐19 on endothelial function in unique cohorts such as young athletes have been largely unexplored. This study evaluated endothelium function by noninvasive flow‐mediated dilation (FMD) in a sample of 14 college athletes (10M/4F, 18‐23 yrs, BMI, 23.8 ± 1.6 kg/m2) after testing positive for Covid‐19. All athletes had Covid‐19 with mild or no symptoms and did not require hospitalization. The study was performed 24 ± 10 days (13‐44 days) after having Covid‐19 positive tests. We also involved 10 BMI similar healthy young subjects as controls (7M/3F, 20‐25 yrs, BMI, 24.2±2.0 kg/m2). Baseline brachial artery diameters and the largest diameters after post cuff release were measured to calculate FMD. Brachial blood flow mean velocities and diameters were also recorded within 20 seconds after cuff release for calculating the shear rate (8 * mean velocity/ diameter). The baseline brachial artery diameter was significantly larger in the athlete group versus the control group (4.32±0.63 mm vs. 3.54±0.42 mm, p=0.02). The FMD was significantly lower in the athlete group than in the control group (6.49±2.05% vs. 11.05±4.08%, p=0.02). This finding is consistent with the previous reports that FMD was significantly lower in healthy athletes compared with controls. However, FMD adjusted for the ratio of flow‐mediated dilation and shear rate did not show a statistical difference between groups (0.058±0.028 %/s‐1 vs. 0.076±0.056 %/s‐1, p=0.33), even after evaluating baseline diameter as a covariate. Despite the need for extended acute and chronic observations and a healthy athlete control group, our findings suggest endothelial resilience in response to Covid‐19 infection in young athletes, which may explain their mild or asymptomatic status. [ABSTRACT FROM AUTHOR]

R2656 --> 560.3 --> Background: During exercise, blood pressure increases via augmented central command and stimulation of mechano‐ and metabosensitive muscle afferents (i.e., the exercise pressor reflex). Recent evidence has reported a strong role of acid sensing ion channels (ASIC's) in mediating this reflex, as well as exercise induced muscle pain. Therefore, it is logical to suspect that inhibiting ASIC's would mitigate the exaggerated blood pressure responses and exercise related muscle pain observed in individuals with peripheral artery disease (PAD). Purpose:. We tested the hypothesis that a single 10mg dose of amiloride (a K+‐sparing diuretic known to inhibit ASIC's) would attenuate the pressor response to blood flow restricted (BFR) plantar flexion exercise in young healthy adults. Methods: Six healthy subjects (5 male, 26 ± 2 y/o, 180.8 ± 12.1 cm, 79.7 ± 12.9 Kg) completed three separate visits. Each visit included two bouts of isometric plantar flexion, both performed until failure at 30% of the predetermined maximal voluntary isometric contraction. During one bout, blood flow to the limb was restricted via a pressurized cuff placed around the proximal portion of the lower leg (BFR); the other bout was performed under free flow conditions. In the first visit, subjects performed these two exercise bouts (in random order) under normal, non‐treated conditions. In the second and third visits, subjects performed these exercise bouts (same order as in visit 1) ~3 hrs after oral ingestion of 10mg of amiloride, or ingestion of a placebo (random order). Blood pressure and heart rate were continuously recorded throughout exercise, and time to fatigue and muscle pain (on a 12cm visual analog scale) was recorded at the end of each exercise bout. Only data from the placebo and amiloride conditions are presented here. Results: The addition of BFR reduced total exercise time by ~40.8% (t=2.99, p=0.03), but had no significant effect on peak muscle pain (p>0.10). Due to the preliminary nature of these data, no significant main effects of treatment (amiloride vs. placebo) were observed for free flow or BFR exercise (all p>0.05). However, we did observe a net decrease in the average heart rate response (+10.7 ± 3.0 bpm vs. +11.3 ± 3.7 bpm, ηp2=0.539, p>0.47), the total blood pressure response (5477.5 ± 373.7 mmHg*sec vs. 5841.3 ± 518.9 mmHg*sec, ηp2=0.250, p>0.30), the total time‐tension index (595.9 ± 406.5 Kg*sec vs. 691.6 ± 394.2 Kg*sec, ηp2=0.211, p>0.30), and the blood pressure to time‐tension index relationship (9.09 ± 4.40 mmHg/Kg vs. 11.38 ± 6.30 mmHg/Kg, ηp2=0.08, p>0.50) in the amiloride condition compared to the placebo condition during BFR exercise. Conclusions: While these preliminary findings do not indicate significant effects of treatment, these observations serve as strong pilot data to support the continued investigation of amiloride as a method of attenuating the pressor response to ischemic exercise. [ABSTRACT FROM AUTHOR]

R2277 --> 733.14 --> It is well‐known that hyperoxia evokes different effects in patients with different dieaseas conditions. Studies from this lab and others have shown that hyperoxia is a potent coronary vasoconstrictor. Recently, we found that hyperoxia exaggerates systolic blood pressure (BP) response in patients with PAD. The aim of this study is to characterize the coronary circulatory effects of hyperoxia in PAD patients and healthy controls. We recruited 20 PAD patients (14M, 6F, 66 ± 6yrs), and 16 age‐matched control subjects (10M, 6F, 65 ± 8yrs). The ankle‐brachial pressure index (ABI) in the most affected limbs of the patients was 0.58 ± 0.15, compared to the controls ABI of 1.04 ± 0.09. For the hyperoxia procedure the subjects breathed room air for three minutes and 100% oxygen for five minutes. BP and heart rate (HR) were monitored during baseline and hyperoxia. The rate pressure product (RPP), an index of myocardial oxygen consumption, was calculated as the product of systolic BP and HR. Transthoracic Coronary Echocardiography was used to record early and late peak coronary blood flow velocities (CBV1 and CBV2) in the left anterior descending artery. Early and late coronary vascular conductances (peak coronary blood velocity/diastolic blood pressure, CVC1 and CVC2) and coronary perfusion time fraction (CPTF, coronary perfusion time/R‐R interval) were calculated. All data was compared across time and between groups using Repeated Measures Analyses of Variance (RMANOVA). Results: At the baseline, RPP and coronary parameters (CBV2, CVC1, and CVC2) were higher in the PAD group compared to controls, also the PAD group showed significantly shorter CPTF. During hyperoxia, CBV1, CBV2, CVC1, and CVC2 decreased to varying degrees in both groups. However, no significant interactions were observed for RPP and all coronary parameters during hyperoxia between the groups (Table). Our findings suggest that the effect of hyperoxia on coronary circulation was not significantly different between PAD and healthy controls. [ABSTRACT FROM AUTHOR]