Systemic Vascular Conductance Research Articles

Vascular limitations in blood pressure regulation with age in women: Insights from exercise and acute cardioselective β-blockade.

Younger women rely on altering cardiac output ( ) 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 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 β1-antagonist, or saline control in a repeated-measures crossover design. 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.

Heat-related changes in the velocity and kinetic energy of flowing blood influence the human heart's output during hyperthermia.

Passive whole-body hyperthermia increases limb blood flow and cardiac output ( ), but the interplay between peripheral and central thermo-haemodynamic mechanisms remains unclear. Here we tested the hypothesis that local hyperthermia-induced alterations in peripheral blood flow and blood kinetic energy modulate flow to the heart and . Body temperatures, regional (leg, arm, head) and systemic haemodynamics, and left ventricular (LV) volumes and functions were assessed in eight healthy males during: (1) 3h control (normothermic condition); (2) 3h of single-leg heating; (3) 3h of two-leg heating; and (4) 2.5h of whole-body heating. Leg, forearm, and extracranial blood flow increased in close association with local rises in temperature while brain perfusion remained unchanged. Increases in blood velocity with small to no changes in the conduit artery diameter underpinned the augmented limb and extracranial perfusion. In all heating conditions, increased in association with proportional elevations in systemic vascular conductance, related to enhanced blood flow, blood velocity, vascular conductance and kinetic energy in the limbs and head (all R2≥0.803; P<0.001), but not in the brain. LV systolic (end-systolic elastance and twist) and diastolic functional profiles (untwisting rate), pulmonary ventilation and systemic aerobic metabolism were only altered in whole-body heating. These findings substantiate the idea that local hyperthermia-induced selective alterations in peripheral blood flow modulate the magnitude of flow to the heart and through changes in blood velocity and kinetic energy. Localised heat-activated events in the peripheral circulation therefore affect the human heart's output. KEY POINTS: Local and whole-body hyperthermia increases limb and systemic perfusion, but the underlying peripheral and central heat-sensitive mechanisms are not fully established. Here we investigated the regional (leg, arm and head) and systemic haemodynamics (cardiac output: ) during passive single-leg, two-leg and whole-body hyperthermia to determine the contribution of peripheral and central thermosensitive factors in the control of human circulation. Single-leg, two-leg, and whole-body hyperthermia induced graded increases in leg blood flow and . Brain blood flow, however, remained unchanged in all conditions. Ventilation, extracranial blood flow and cardiac systolic and diastolic functions only increased during whole-body hyperthermia. The augmented with hyperthermia was tightly related to increased limb and head blood velocity, flow and kinetic energy. The findings indicate that local thermosensitive mechanisms modulate regional blood velocity, flow and kinetic energy, thereby controlling the magnitude of flow to the heart and thus the coupling of peripheral and central circulation during hyperthermia.

Calf Venous Compliance During Hypotension After an Acute bout of Aerobic Exercise in Humans

Abstract Purpose Post-exercise hypotension (PEH) following prolonged dynamic exercise is induced by an increase in systemic vascular conductance via skeletal muscle vasodilation, which may occur not only in the arteries but also in the veins, and the vasodilated regions may contribute to greater venous pooling in the exercised limbs. However, the contribution of venous distention to PEH is unclear. Therefore, we aimed to evaluate venous compliance in previously exercised muscles in a preliminary study. Methods Seven participants performed a single 60-min session of upright cycle ergometry at 60% of heart rate reserve. Calf venous compliance was measured using venous congestion plethysmography before and 45 min following exercise in Trial 1. Stroke volume and femoral arterial blood flow were determined using ultrasonography at the same time points in Trial 2. Heart rate and blood pressure were monitored during both trials. Results Mean arterial pressure significantly decreased between the start and ~ 30 min following the end of exercise (82 ± 6 mmHg vs. 76 ± 6 mmHg, respectively, in Trial 1; 79 ± 6 mmHg vs. 74 ± 5 mmHg, respectively, in Trial 2; P &lt; 0.05). Pre- and post-exercise stroke volume did not significantly differ. Blood flow and vascular conductance in the femoral artery significantly increased from 641 ± 84 mL/min and 8.13 ± 0.79 mL/min/mmHg pre-exercise to 773 ± 121 mL/min and 10.55 ± 1.00 mL/min/mmHg post-exercise, respectively (P &lt; 0.05). Pre- and post-exercise calf venous compliance did not significantly differ. Conclusion Our findings demonstrate that vasodilation in the active limb increases during exercise, but the resulting PEH does not affect venous compliance.

Postexercise cardiovascular hemodynamics assessment before and after a 30-minute standing still recovery.

Although postexercise syncope usually occurs shortly after physical exercise conclusion, athletes commonly reveal symptoms of postexercise hypotension several tens of minutes after exercise completion. Currently, no studies have investigated central hemodynamic regulation during posture changes occurring several tens of minutes after exercise compared to immediately after cessation. This study examined changes in mean arterial pressure (MAP), heart rate (HR), systemic vascular conductance (SVC), cardiac output, and stroke volume during two sets of tilt tests performed before vs. after a 30-minute standing still recovery, respectively. Tilt tests were performed after a short-lasting supramaximal test (WNG) and long-lasting maximal incremental test (INC) in 12 young endurance-trained individuals. The key findings were that, regardless of the exercise type, the 30-minute recovery augmented (P<0.01) the increase in HR and the drop in SVC during the transition from supine to upright, although the MAP drop was similar (P=0.99) after vs. before recovery. INC led to greater increases (P<0.01) in HR and drops (P<0.01) in SVC compared to WNG during postural transitions both before and after the recovery. These findings suggest that, in a population that tolerates postexercise hypotension, MAP neural control is more challenged after a 30-minute standing still recovery than before, as evidenced by an augmented vasodilation capacity along with an increased HR buffering response during posture changes. Moreover, our data suggest that effective MAP control is resulting from an equally effective HR buffering response on MAP. Therefore, exercises that induce greater systemic vasodilation lead to greater HR buffering responses.

The exercise pressor reflex - a pressure-raising mechanism with a limited role in regulating leg perfusion during locomotion in young healthy men.

We investigated the role of the exercise pressor reflex (EPR) in regulating the haemodynamic response to locomotor exercise. Eight healthy participants (23±3years, : 49±6ml/kg/min) performed constant-load cycling exercise (∼36/43/52/98% ; 4min each) without (CTRL) and with (FENT) lumbar intrathecal fentanyl attenuating group III/IV locomotor muscle afferent feedback and, thus, the EPR. To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during FENT, subjects mimicked the ventilatory response recorded during CTRL. Arterial and leg perfusion pressure (femoral arterial and venous catheters), femoral blood flow (Doppler-ultrasound), microvascular quadriceps blood flow index (indocyanine green), cardiac output (inert gas breathing), and systemic and leg vascular conductance were quantified during exercise. There were no cardiovascular and ventilatory differences between conditions at rest. Pulmonary ventilation, arterial blood gases and oxyhaemoglobin saturation were not different during exercise. Furthermore, cardiac output (-2% to -12%), arterial pressure (-7% to -15%) and leg perfusion pressure (-8% to -22%) were lower, and systemic (up to 16%) and leg (up to 27%) vascular conductance were higher during FENT compared to CTRL. Leg blood flow, microvascular quadriceps blood flow index, and leg O2 -transport and utilization were not different between conditions (P>0.5). These findings reflect a critical role of the EPR in the autonomic control of the heart, vasculature and, ultimately, arterial pressure during locomotor exercise. However, the lack of a net effect of the EPR on leg blood flow challenges the idea of this cardiovascular reflex as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals. KEY POINTS: The role of the exercise pressor reflex (EPR) in regulating leg O2 -transport during human locomotion remains uncertain. We investigated the influence of the EPR on the cardiovascular response to cycling exercise. Lumbar intrathecal fentanyl was used to block group III/IV leg muscle afferents and debilitate the EPR at intensities ranging from 30% to 100% . To avoid different respiratory muscle metaboreflex and arterial chemoreflex activation during exercise with blocked leg muscle afferents, subjects mimicked the ventilatory response recorded during control exercise. Afferent blockade increased leg and systemic vascular conductance, but reduced cardiac output and arterial-pressure, with no net effect on leg blood flow. The EPR influenced the cardiovascular response to cycling exercise by contributing to the autonomic control of the heart and vasculature, but did not affect leg blood flow. These findings challenge the idea of the EPR as a key determinant of leg O2 -transport during locomotor exercise in healthy, young individuals.

Attenuated pulsatile transition to the cerebral vasculature during high-intensity interval exercise in young healthy men.

What is the central question of this study? High-intensity interval exercise (HIIE) is recommended for its favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may stress the brain: is the cerebral vasculature protected against exaggerated systemic blood flow fluctuation during HIIE? What is the main finding and its importance? Time- and frequency-domain indices of aortic-cerebral pulsatile transition were lowered during HIIE. The findings suggest that the arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature. High-intensity interval exercise (HIIE) is recommended because it provides favourable haemodynamic stimulation, but excessive haemodynamic fluctuations may be an adverse impact on the brain. We tested whether the cerebral vasculature is protected against systemic blood flow fluctuation during HIIE. Fourteen healthy men (age 24 ± 2 years) underwent four 4-min exercises at 80-90% of maximal workload (Wmax ) interspaced by 3-min active rest at 50-60% Wmax . Transcranial Doppler measured middle cerebral artery blood velocity (CBV). Systemic haemodynamics (Modelflow) and aortic pressure (AoP, general transfer function) were estimated from an invasively recorded brachial arterial pressure waveform. Using transfer function analysis, gain and phase between AoP and CBV (0.39-10.0Hz) were calculated. Stroke volume, aortic pulse pressure and pulsatile CBV increased during exercise (time effect: P<0.0001 for all), but a time-domain index of aortic-cerebral pulsatile transition (pulsatile CBV/pulsatile AoP) decreased throughout the exercise bouts (time effect: P<0.0001). Furthermore, transfer function gain reduced, and phase increased throughout the exercise bouts (time effect: P<0.0001 for both), suggesting the attenuation and delay of pulsatile transition. The cerebral vascular conductance index (mean CBV/mean arterial pressure; time effect: P=0.296), an inverse index of cerebral vascular tone, did not change even though systemic vascular conductance increased during exercise (time effect: P<0.0001). The arterial system to the cerebral vasculature may attenuate pulsatile transition during HIIE as a defence mechanism against pulsatile fluctuation for the cerebral vasculature.

Systemic Cardiovascular Adjustments during Recovery from Passive Heat Stress

Much like exercise, heat stress elicits profound autonomic and hemodynamic responses which may persist in the post‐heating recovery period. In the same way that the post‐exercise recovery period contributes to vascular adaptation with exercise training, the post‐heating recovery period may potentiate beneficial vascular adaptation with chronic heat therapy. In contrast to the well‐studied post‐exercise recovery period, few studies have investigated the systemic cardiovascular adjustments accompanying recovery from whole‐body, passive heat stress. Hypothesis: We hypothesized that mean arterial pressure would be reduced in the post‐heating recovery period due to sustained post‐heating elevations in systemic vascular conductance and despite elevations in cardiac output.MethodsFour subjects (1 F, 27±5 yrs, BMI 26±3 kg/m2) completed two experimental visits (randomized, crossover design) comprising either 60 min of passive heating (HT) or a time‐matched thermoneutral control intervention (TN). Rectal temperature, skin temperature (six sites), brachial blood pressure, cardiac output (open‐circuit acetylene washin method), and heart rate were assessed at baseline, at the end of HT or TN interventions, and for 2 hours of recovery in a 21.4±0.4°C room (REC‐HT/TN). Values are reported as the change in each variable from pre‐intervention baseline and presented as means ± SD. Paired t tests were used to compare responses between conditions.ResultsHeating increased mean body temperature (HT +1.26±0.23°C, TN ‐0.04±0.07°C) (P &lt; 0.001). After 40 min of recovery, mean body temperature tended to remain elevated following heating (HT +0.48±0.18, TN +0.19±0.09°C, P = 0.06). There were no differences in mean body temperature between conditions at 80 min (P = 0.31) or 120 min of recovery (P = 0.37). Mean arterial pressure was reduced at the end of heating (HT ‐12±6, TN +5±4 mmHg, P &lt; 0.01) as elevations in systemic vascular conductance (HT +55±18, TN ‐6±6 mL·min‐1·mmHg‐1, P &lt; 0.01) were not offset by increases in cardiac output (HT +3.5±0.8, TN ‐0.2±0.6 L/min, P &lt; 0.01) sustained by an increased heart rate (HT +40±8, TN ‐2±6 bpm, P &lt; 0.01). Mean arterial pressure tended to remain reduced 40 min into the post‐heating recovery period (REC‐HT ‐6±6, REC‐TN +1±3 mmHg, P = 0.16) due to a tendency for elevations in systemic vascular conductance (REC‐HT +11±21, REC‐TN ‐6±15 mL·min‐1·mmHg‐1, P = 0.08). Cardiac output (REC‐HT +0.5±1.5, REC‐TN ‐0.5±1.1 L/min, P = 0.07) and heart rate (REC‐HT +6±9, REC‐TN ‐3±5 bpm, P = 0.07) also appeared to remain elevated 40 min into the post‐heating recovery period. Mean arterial pressure appeared similar between conditions from 80 minutes of recovery onward (P = 0.85) while systemic vascular conductance (P = 0.12) and cardiac output (P = 0.19) tended to remain elevated. These variables appeared similar between conditions after 120 min of recovery.ConclusionsRecovery from heat stress is marked by sustained hypotension, vasodilation, and elevations in cardiac output and heart rate. These post‐heating recovery responses may facilitate vascular adaptation with heat therapy.

Efficacy of Hot Water Immersion versus Aerobic Exercise Training in Lowering Blood Pressure and Improving Cardiovascular Function in Adults with Untreated Hypertension

INTRODUCTIONHypertension remains among the most prevalent cardiovascular disease risk factors world‐wide. Aerobic exercise training is the current gold‐standard non‐pharmacological intervention for lowering blood pressure, yet passive heat therapy is an effective alternative means of reducing blood pressure and improving cardiovascular health for individuals that are unable or unwilling to engage in traditional exercise training. However, the effectiveness of heat therapy versus exercise training has not been compared in adults with untreated hypertension. Therefore, the purpose of this ongoing clinical trial is to compare the effectiveness of hot water immersion (HWI) versus aerobic exercise training (EX) in lowering blood pressure and improving cardiovascular function. Data presented are preliminary (mid‐point) comparisons following 15 sessions of either HWI or EX.HYPOTHESISIt was hypothesized that hot water immersion would be more effective than traditional aerobic exercise training in reducing blood pressure and improving cardiovascular function in adults with untreated hypertension.METHODSPrior to randomization, all subjects (n=6, 1F) completed resting vascular function testing, including measurements of blood pressure (automated sphygmomanometer), cardiac output (acetylene wash‐in method), and carotid‐femoral pulse wave velocity (PWV). Systemic vascular conductance (SVC) was calculated as cardiac output/mean arterial pressure (MAP). Following pre‐testing (PRE), subjects were randomized into either HWI (n=4, 1F) or EX (n=2). During HWI, subjects were immersed to the level of the sternum in 40.5°C water for 45 minutes. EX consisted of upright cycling at 60% of heart rate reserve (HRR) for 40 min, with 5 min each for warm‐up and cool‐down at 30% of HRR. Participants completed 15 sessions of either HWI or EX prior to mid‐point (MID) testing. Combined data are presented as the change from PRE as mean ± SD and were analyzed using a paired‐samples t test. Group mean data for HWI versus EX are presented as the change from PRE as means ± SD and were analyzed using an unpaired two sample t‐test.RESULTSFollowing 15 sessions of either HWI or EX, systolic blood pressure tended to be reduced (‐5±4 mmHg; p=0.10). The change in systolic blood pressure (SBP) was directionally similar between HWI and EX (∆ from PRE, HWI vs. EX; ‐3±5 vs. ‐7±7 mmHg; p=0.59), whereas the change in diastolic blood pressure (DBP) was divergent between HWI and EX (‐3±8 vs. +5±10 mmHg; p=0.43). Accordingly, changes in MAP were disparate between HWI and EX (‐3±7 vs. +2±9 mmHg; p=0.61). Cardiac output was similar between HWI and EX (‐0.09±0.71 vs. ‐0.76±1.07 L/min; p=0.53), as were changes in SVC (‐0.3±6.6 vs. ‐7.6±15.9 mL•min‐1•mmHg‐1; p=0.63). Overall, PWV was reduced by both interventions (‐0.6±0.3 m/s; p=0.01) and changes in PWV were similar between HWI and EX (‐0.6±0.4 vs. ‐0.5±0.4 m/s; p=0.72).CONCLUSIONSPreliminary data from this ongoing clinical trial suggest both hot water immersion and exercise are similarly effective in lowering systolic blood pressure and reducing arterial stiffness in people with untreated hypertension.

The baroreflex in aquatic and amphibious teleosts: Does terrestriality represent a significant driving force for the evolution of a more effective baroreflex in vertebrates?

All vertebrates have baroreflexes that provide fast regulation of arterial blood pressure (PA) to maintain adequate tissue perfusion and avoid vascular lesions from excessive pressures. The baroreflex is a negative feedback loop, where altered PA results in reciprocal changes in heart rate (fH) and systemic vascular conductance to restore pressure. In terrestrial environments, gravity usually leads to blood pooling in the lower body reducing venous return, cardiac filling, cardiac output and PA. Conversely, in aquatic environments, the hydrostatic pressure of surrounding water mitigates blood pooling and prevents vascular distensions. In this context, we aimed to test the hypothesis that vertebrate species that were exposed to gravity-induced hemodynamic disturbances throughout their evolutionary histories have a more effective barostatic reflex than those that were not. We examined the cardiac baroreflex of fish that perform (Clarias gariepinus and Hoplerythrinus unitaeniatus) and do not perform (Hoplias malabaricus and Oreochromis niloticus) voluntary terrestrial sojourns, using pharmacological manipulations of PA to characterize reflex changes in fH using a four-variable sigmoidal logistic function (i.e. the “Oxford technique”). Our results revealed that amphibious fish exhibit higher baroreflex gain and responsiveness to hypotension than strictly aquatic fish, suggesting that terrestriality and the gravitational circulatory stresses constitute a relevant driving force for the evolution of a more effective baroreflex in vertebrates. We also demonstrate that strictly aquatic teleosts have considerable baroreflex gain, supporting the view that the baroreflex is an ancient cardiovascular trait that appeared before vertebrates colonized the gravity-dominated realm of land.

Effect of Acute Leg Heating On Circulating Endothelin‐1 in Aged Humans

There is a sustained reduction in arterial blood pressure that occurs in aged adults following exposure to acute leg heating. However, the neurovascular and humoral mechanisms mediating this hypotensive response remain unknown. The purpose of this study was to test the hypothesis that circulating concentrations of the potent vasoconstrictor substance endothelin‐1 would be attenuated concurrently with arterial blood pressure in aged adults following exposure to acute leg heating. Thirteen young adults (6 female; age 25 ± 4; height 172 ± 9 cm; weight 74 ± 15 kg; mean ± SD) and 10 aged adults (6 female; age 69 ± 5; height 166 ± 4 cm; weight 71 ± 11 kg; mean ± SD) were exposed to 45 minutes of acute leg heating. Subjects wore a tube‐lined water‐circulating garment that allowed leg skin temperature to be clamped at ~40°C during heating. Intestinal temperature was measured throughout via a telemetric pill. Systemic vascular conductance was calculated as cardiac output divided by mean arterial pressure and measured prior to heating (pre‐heat) and 30 min after (recovery). Plasma endothelin‐1 concentrations were quantified at pre‐heat and recovery time points via an enzyme‐linked immunosorbent assay. Leg heating increased body core temperature in young adults by 0.4 ± 0.1 °C and by 0.8 ± 0.2 °C in aged adults (both P &lt; 0.05 vs. 0 change). Body core temperature remained modestly elevated for both groups in recovery (both P &lt; 0.05 vs. pre‐heat). Mean arterial blood pressure was well maintained in young adults following leg heating (pre‐heat, 86 ± 6 mmHg vs. recovery, 88 ± 7 mmHg; P = 0.4), but was markedly reduced in aged adults (pre‐heat, 101 ± 7 mmHg vs. recovery, 94 ± 6 mmHg; P &lt; 0.05). Systemic vascular conductance in young adults did not differ from pre‐heat (69 ± 3 ml min−1 mmHg−1) to recovery (70 ± 3 ml min−1 mmHg−1; P = 0.7), whereas conductance was increased in aged adults (pre‐heat, 55 ± 6 ml min−1 mmHg−1 vs. recovery, 62 ± 5 ml min−1 mmHg−1; P = 0.07). Plasma endothelin‐1 concentrations did not differ between groups at the pre‐heat time point (young adults, 1.13 ± 0.13 pg ml−1 vs. aged adults, 1.44 ± 0.11 pg ml−1; P = 0.4). Plasma endothelin‐1 increased in recovery by 0.23 ± 0.42 pg ml−1 for young adults and by 0.20 ± 0.43 pg ml−1 for aged adults (both P &lt; 0.05 vs. 0 change). These data suggest that increased circulating endothelin‐1 may contribute to the maintenance of arterial blood pressure in young adults following exposure to acute leg heating by limiting systemic vascular conductance. Despite an increase in plasma endothelin‐1 in aged adults, arterial blood pressure was reduced in parallel with an increase in systemic vascular conductance which suggests that endothelin‐1‐mediated vasoconstriction may be altered following leg heating. Alternatively, increased endothelin‐1 may be preventing a further deleterious reduction in arterial blood pressure in aged adults by restraining the increase in systemic vascular conductance.Support or Funding InformationNational Institutes of Health (R01AG059314) and laboratory startup funds from the University of North Texas Health Science Center.

Effects of exercise training and sex on dynamic responses of O2 uptake in type 2 diabetes.

Effects of training and sex on oxygen uptake dynamics during exercise in type 2 diabetes mellitus (T2DM) are not well established. We tested the hypotheses that exercise training improves the time constant of the primary phase of oxygen uptake (τp oxygen uptake) and with greater effect in males than females. Forty-one subjects with T2DM were assigned to 2 training groups (Tmale, Tfemale) and 2 control groups (Cmale, Cfemale), and were assessed before and after a 12-week intervention period. Twelve weeks of aerobic/resistance training was performed 3 times per week, 60-90 min per session. Assessments included ventilatory threshold (VT), peak oxygen uptake, τp oxygen uptake (80%VT), and dynamic responses of cardiac output, mean arterial pressure and systemic vascular conductance (80%VT). Training significantly decreased τp oxygen uptake in males by a mean of 20% (Tmale = 42.7 ± 6.2 to 34.3 ± 7.2 s) and females by a mean of 16% (Tfemale = 42.2 ± 9.3 to 35.4 ± 8.6 s); whereas τp oxygen uptake was not affected in controls (Cmale = 41.6 ± 9.8 to 42.9 ± 7.6 s; Cfemale = 40.4 ± 12.2 to 40.6 ± 13.4 s). Training increased peak oxygen uptake in both sexes (12%-13%) but did not alter systemic cardiovascular dynamics in either sex. Training improved oxygen uptake dynamics to a similar extent in males and females in the absence of changes in systemic cardiovascular dynamics. Novelty Similar training improvements in oxygen uptake dynamics were observed in males and females with T2DM. In both sexes these improvements occurred without changes in systemic cardiovascular dynamics.

Does Capsaicin Ingestion Affect Functional Sympatholysis And Vascular Functions?

During exercise, heat and metabolites (e.g. H+, etc.) attenuate sympathetically-mediated vasoconstriction in contracting muscle, known as functional sympatholysis, remains poorly understood. Previous work has shown that activation of transient receptor potential vanilloid type 1 channels (TRPV1) with Capsaicin (CAP, spicy ingredient in peppers), elicits a sympatholytic effect in vitro in humans. PURPOSE: To determine if acute ingestion of CAP elicits or enhances sympatholysis at rest and during exercise in vivo in humans. METHODS: In a single blind crossover design, in 10 young healthy males we measured forearm microvascular responses (oxyhemoglobin and myoglobin HbO2+MbO2) using near infrared spectroscopy (NIRS) and central/peripheral hemodynamic (cardiac output, CO, and mean arterial pressure, MAP, via Finometer) responses at rest, lower body negative pressure at rest (rLBNP), rhythmic handgrip (HG) exercise at 30% MVC and during HG with LBNP (HG+LBNP) under placebo (PL, 800 mg fiber) and Capsaicin (780 mg pepper extract). RESULTS: No differences (P>0.05) were found between PL and CAP in microvascular and central hemodynamics at rest. At rest the LBNP-induced change in HbO2+MbO2 (-1.5 ± 2.3 vs 0.3 ± 2.3 %∆) or conductance index (HbO2+MbO2/MAP: 5.5 ± 2 vs 6.0 ± 3 %∆) were not different (P>0.05). During exercise, HbO2+MbO2 were not different (105 ± 28 vs 105 ± 21 uM), though tissue oxygen saturation tended to be higher (64 ± 16 vs 70 ± 13 %, P=0.07), and deoxyhemoglobin lower in CAP (44 ± 5 vs 37 ± 4 uM, P=0.05). The LBNP-induced change during exercise in HbO2+MbO2 (-0.1 ± 7.1 vs 1.3 ± 7.2 %∆) or conductance (5.6 ± 3 vs 2.8 ± 4 %∆) were not significant (P>0.05), but tended to be better in CAP. Systemic vascular conductance was not significant different at rest between conditions (5.3 ± 0.2 vs. 4.8 ± 0.4 L/min/mmHg). The LBNP-induced change in SVC at rest (5.6 ± 5.5 vs 6.1 ± 5.7 %∆) and during exercise (5.2 ± 2.4 vs 1.7 ± 5.2 %∆), were not different, despite a tendency to be attenuated during exercise with CAP. CONCLUSION: Acute CAP does not affect resting hemodynamics or the response to sympathoexcitatory LBNP. During exercise, CAP seems to improve microvascular responses, but does not impact the response to LBNP, despite trends for CAP to mitigate the LBNP-induced reductions in both systemic and local conductance.

Long term effects of chronic prenatal exposure to hypercarbia on organ growth and cardiovascular responses to adrenaline and hypoxia in common snapping turtles

Reptilian embryos often face challenging environmental gas compositions during incubation, which may inflict long-lasting effects in the individuals' physiological responses. These conditions can have a lasting effect on the animal into juvenile life as chronic prenatal exposure to hypercarbia results in enlarged hatchling organ size, higher growth rate and resting metabolic rate, although relatively smaller increment in metabolic scope during digestion. Therefore, we wanted to verify whether prenatal hypercarbia exposure would cause persistent effects on morphology and physiological responses in C. serpentina. We measured organ masses and cardiovascular parameters in five years old turtles incubated either under 3.5% hypercarbia (H3.5) or normoxia (N21). We expected that: i) organ masses of H3.5 would be bigger than N21; ii) acute exposure to hypoxia should decrease blood flows in H3.5, since metabolic scope is presumably reduced in this group. As hypoxia exposure elicits catecholamine release, we also tested cardiovascular responses to adrenaline injection. Lungs and stomach exhibited higher growth rates in H3.5. Divergent cardiovascular responses between groups to adrenaline injection were observed for heart rate, pulmonary blood flow, pulmonary mean arterial pressure, blood shunt, systemic stroke volume, and stomach perfusion. Hypoxia caused decreased systemic blood flow and cardiac output, systemic and total stroke volume, and systemic vascular conductance in H3.5. These variables were unaffected in N21, but pulmonary flow and stroke volume, and stomach blood perfusion were reduced. These data support the hypothesis that exposure to hypercarbia during embryonic development has long term effects on organ morphology and cardiovascular responses of C. serpentina.

Effect of Acute Leg Heating on Neurovascular Control in Aged Humans

There is a sustained reduction in arterial blood pressure that occurs in aged adults following acute exposure to leg heating. Concurrent with this blood pressure response is an increase in systemic vascular conductance that is not fully offset by an increase in cardiac output, which suggests that acute leg heating may alter neurovascular control. Therefore, the purpose of this study was to test the hypothesis that acute leg heating reduces sympathetic neurovascular transduction in aged humans. Six healthy young adults (3 females; age 25 ± 4 yrs; height 175 ± 9 cm; weight 74 ± 17 kg; mean ± SD) and 4 healthy aged adults (3 females; age 69 ± 4 yrs; height 163 ± 3 cm; weight 66 ± 7 kg) were exposed to 45 min of acute leg heating. Subjects wore a tube‐lined water‐circulating garment that allowed leg skin temperature to be clamped at ~40 °C during heating. Intestinal temperature was measured throughout via a telemetric pill. Systemic vascular conductance was calculated as cardiac output (Modelflow) divided by mean arterial pressure. Femoral vascular conductance was calculated as blood flow (Doppler ultrasound) divided by mean arterial pressure. Neurovascular transduction was estimated before and 30 min after leg heating by measuring the percent reduction in femoral vascular conductance (ΔFVC) during isometric handgrip exercise performed to fatigue. Compared to pre‐heat, intestinal temperature was increased for both groups at 45 min of leg heating (young adults, Δ0.5 ± 0.1 °C; aged adults, Δ0.9 ± 0.2 °C; both P &lt; 0.05 vs. 0 change) and remained elevated 30 min after heating (young adults, Δ0.3 ± 0.1 °C; aged adults, Δ0.5 ± 0.2 °C; both P &lt; 0.05 vs. 0 change). Thirty min after heating, mean arterial pressure did not differ from pre‐heat in young adults (pre 86 ± 3 mmHg vs. post 87 ± 3 mmHg; P = 0.9) but was decreased in aged adults (pre 102 ± 3 mmHg vs. post 96 ± 2 mmHg; P = 0.06). Resting systemic vascular conductance (pre 65.8 ± 3.6 ml min−1 mmHg−1 vs. post 66.4 ± 4.5 ml min−1 mmHg−1; P = 1.0) and femoral vascular conductance (pre 3.1 ± 0.4 ml min−1 mmHg−1 vs. post 3.3 ± 0.6 ml min−1 mmHg−1; P = 0.5) did not differ from pre‐heat in young adults. However, in aged adults, both resting systemic vascular conductance (pre 46.5 ± 3.7 ml min−1 mmHg−1 vs. post 59.2 ± 8.8 ml min−1 mmHg−1; P = 0.03) and femoral vascular conductance (pre 2.6 ± 0.6 ml min−1 mmHg−1 vs. post 3.4 ± 0.6 ml min−1 mmHg−1; P = 0.07) remained elevated 30 min after heating. Neurovascular transduction was reduced after heating in both groups (young adults, pre ΔFVC −28 ± 8 % vs. post ΔFVC −13 ± 10 %; aged adults, pre ΔFVC −30 ± 6 % vs. post ΔFVC −23 ± 7 %; P = 0.03). Taken together, it appears that the reduction in arterial blood pressure that occurs in aged adults after acute leg heating is mediated by a persistent vasodilation that is due, at least in part, to reduced neurovascular transduction. In young adults, blood pressure is well maintained after leg heating despite reduced neurovascular transduction, which may be related to an increase in basal sympathetic vasoconstrictor outflow.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Alternative Approaches to the Assessment of the Systemic Circulation and Left Ventricular Performance: A Proof-of-Concept Study

BackgroundThe purpose of this article is to examine the systemic circulation and left ventricular (LV) performance by alternative, nonconventional approaches: systemic vascular conductance (GSV) and the head-capacity relation (ie, the relation between LV pressure and cardiac output), respectively; in so doing, we aspired to present a novel and improved interpretation of integrated cardiovascular function. MethodsIn 16 open-chest, anaesthetized pigs, we measured LV pressure (PLV), central aortic pressure (PAo), and central venous pressure (PCV) and aortic flow (QAo). We calculated heart rate (HR), stroke volume, cardiac index (CI = cardiac output/body weight), mean PLV (P¯LV), and the average arteriovenous pressure difference (ΔP=P¯Ao−P¯CV); GSV = CI/(P¯Ao−P¯CV). We studied the effects of changing loading conditions with the administration of phenylephrine (ΔP¯Ao ≥ +25 mm Hg), isoproterenol (ΔHR ∼+25%), sodium nitroprusside (ΔP¯Ao ≥ −25 mm Hg), and proximal aortic constriction (to maximize developed PLV and minimize QAo). ResultsSodium nitroprusside and isoproterenol increased GSV compared with phenylephrine and constriction. A maximum head-capacity curve was derived from pooled data using nonlinear regression on the maximum P¯LV values in QAo bins 12.5 mL/min/kg wide. The head-capacity relation and the plots of conductance were combined using CI as a common axis, which illustrated that CI is the output of the heart and the input of the circulation. ConclusionsThus, at a given CI, GSV determines the driving pressure and, thereby, PAo. We also demonstrated how decreases in GSV compensate for arterial hypotension by restoring the arteriovenous pressure difference and arterial pressure.

Effect of obesity on oxygen uptake and cardiovascular dynamics during whole-body and leg exercise in adult males and females.

Obesity has been associated with a slowing of V˙O2 dynamics in children and adolescents, but this problem has not been studied in adults. Cardiovascular mechanisms underlying this effect are not clear. In this study, 48 adults (18 males, 30 females) grouped according to body mass index (BMI) (lean < 25 kg·m−2, overweight = 25–29.9 kg·m−2, obese ≥30 kg·m−2) provided a fasting blood sample, completed a maximal graded exercise test and six bouts of submaximal exercise on a cycle ergometer, and performed two protocols of calf exercise. Dynamic response characteristics of V˙O2 and leg vascular conductance (LVC) were assessed during cycling (80% ventilatory threshold) and calf exercise (30% MVC), respectively. Dynamic responses of cardiac output, mean arterial pressure and total systemic vascular conductance were also assessed during cycling based on measurements at 30 and 240 sec. The time constant of the second phase of the V˙O2 response was significantly greater in obese than lean subjects (39.4 (9.2) vs. 29.1 (7.6) sec); whereas dynamic responses of cardiac output and systemic vascular conductance were not affected by BMI. For calf exercise, the time constant of the second growth phase of LVC was slowed significantly in obese subjects (22.1 (12.7) sec) compared with lean and overweight subjects (11.6 (4.5) sec and 13.4 (6.7) sec). These data show that obesity slows dynamic responses of V˙O2 during cycling and the slower phase of vasodilation in contracting muscles of male and female adults.

Metaboreceptor activation in heart failure with reduced ejection fraction: Linking cardiac and peripheral vascular haemodynamics.

What is the central question of this research? Do patients with heart failure with reduced ejection fraction (HFrEF) exhibit a greater dependence on cardiac or peripheral vascular haemodynamics across multiple levels of muscle metaboreflex activation provoked by postexercise circulatory occlusion? What is the main finding and its importance? The metaboreflex-induced pressor response in HFrEF patients is governed almost entirely by the peripheral circulation, which places a substantial haemodynamic load on the failing heart. This maladaptive response exacerbates the disease-related impairment of systolic function that is a hallmark feature of HFrEF and may therefore contribute to exercise intolerance in this patient group. We sought to evaluate the muscle metaboreflex in heart failure with reduced ejection fraction (HFrEF) patients, with an emphasis on the interaction between cardiac and peripheral vascular haemodynamics across multiple levels of metaboreceptor activation. In 23HFrEF patients (63±2years of age) and 15 healthy control subjects (64±3years of age), we examined changes in mean arterial pressure, cardiac output, systemic vascular conductance, effective arterial elastance, stroke work and forearm deoxyhaemoglobin concentration during metaboreceptor activation elicited by postexercise circulatory occlusion (PECO) after three levels of static-intermittent handgrip exercise (15, 30 and 45% maximal voluntary contraction). Across workloads, the metaboreflex-induced increase in deoxyhaemoglobin and mean arterial pressure were similar between groups. However, in control subjects, the pressor response was driven by changes (Δ) in cardiac output(Δ495±155, Δ564±156 and Δ666±217mlmin-1 ), whereas this change was accomplished by intensity-dependent reductions in systemic vascular conductance in patients with HFrEF (Δ-4.9 ±1.5, Δ-9.1 ±1.9 and Δ-12.7 ±1.8mlminmmHg-1 ). This differential response contributed to the exaggerated increases in effective arterial elastance in HFrEF patients compared with control subjects, coupled with a blunted response in stroke work in the HFrEF patients. Together, these findings indicate a preserved role of the metaboreflex-induced pressor response in HFrEF but suggest that this response is governed by changes in the peripheral circulation. The net effect of this response appears to be maladaptive, as it places a substantial haemodynamic load on the left ventricle that may exacerbate left ventricular systolic dysfunction and contribute to exercise intolerance in this patient population.

Cardiac responses to exercise distinguish postural orthostatic tachycardia syndrome variants.

We previously showed that one‐third of adolescents with postural orthostatic tachycardia syndrome (POTS) have hyperkinetic circulation. In a subsequent cohort, we compare participants with POTS grouped according to cardiac output (Q˙) versus oxygen uptake (V˙O2) function, whose circulatory response to exercise lay at the lower end of this distribution. We hypothesized that such grouping determines the circulatory response to incremental‐protocol, upright, cycle ergometry by whatever blend of flow and resistance adjustments best maintains normal blood pressure. We reviewed data on 209 POTS participants aged 10–19 years (73% female) grouped as follows: Q˙−V˙O2 < 3.20 L·min−1 per L·min−1 were designated low Q˙ or hypokinetic variant (N = 31); normal‐Q˙ had slopes between 3.21 and 7.97; hyperkinetic participants had Q˙−V˙O2 slope >8 L·min−1 per L·min−1 (N = 32). Heart rate response to exercise was virtually identical in each group. Mean stroke volume (SV) rose normally in the hyperkinetic group (51 ± 38%); less in the normal Q˙ group (22 ± 27%); but was flat in the low Q˙ group (−7 ± 16%). Mean arterial pressure was similar at rest while systemic vascular conductance was flat from rest to exercise in the hypokinetic group, and by comparison rose more steeply in the normal Q˙ (P < 0.001) and in the hyperkinetic (P = 0.02) groups. In conclusion, we identified a variant of POTS with a hypokinetic circulation maintained by a vasoconstricted state. We speculate that they cannot muster preload to augment exercise SV due to profound thoracic hypovolemia, and must resort to vasoconstriction in order to maintain perfusion pressure within working muscle.

Vagal tone regulates cardiac shunts during activity and at low temperatures in the South American rattlesnake, Crotalus durissus.

The undivided ventricle of non-crocodilian reptiles allows for intracardiac admixture of oxygen-poor and oxygen-rich blood returning via the atria from the systemic circuit and the lungs. The distribution of blood flow between the systemic and pulmonary circuits may vary, based on differences between systemic and pulmonary vascular conductances. The South American rattlesnake, Crotalus durissus, has a single pulmonary artery, innervated by the left vagus. Activity in this nerve controls pulmonary conductance so that left vagotomy abolishes this control. Experimental left vagotomy to abolish cardiac shunting had no effect on long-term survival and failed to identify a functional role in determining metabolic rate, growth or resistance to food deprivation. Accordingly, the present investigation sought to evaluate the extent to which cardiac shunt patterns are actively controlled during changes in body temperature and activity levels. We compared hemodynamic parameters between intact and left-vagotomized rattlesnakes held at different temperatures and subjected to enforced physical activity. Increased temperature and enforced activity raised heart rate, cardiac output, pulmonary and systemic blood flow in both groups, but net cardiac shunt was reversed in the vagotomized group at lower temperatures. We conclude that vagal control of pulmonary conductance is an active mechanism regulating cardiac shunts in C. durissus.

Local and systemic vasodilatory effects of low molecular weight S-nitrosothiols

S-nitrosothiols (SNOs) such as S-nitroso-L-cysteine (L-cysNO) are endogenous compounds with potent vasodilatory activity. During circulation in the blood, the NO moiety can be exchanged among various thiol-containing compounds by S-transnitrosylation, resulting in SNOs with differing capacities to enter the cell (membrane permeability). To determine whether the vasodilating potency of SNOs is dependent upon membrane permeability, membrane-permeable L-cysNO and impermeable S-nitroso-D-cysteine (D-cysNO) and S-nitroso-glutathione (GSNO) were infused into one femoral artery of anesthetized adult sheep while measuring bilateral femoral and systemic vascular conductances. L-cysNO induced vasodilation in the infused hind limb, whereas D-cysNO and GSNO did not. L-cysNO also increased intracellular NO in isolated arterial smooth muscle cells, whereas GSNO did not. The infused SNOs remained predominantly in a low molecular weight form during first-passage through the hind limb vasculature, but were converted into high molecular weight SNOs upon systemic recirculation. At systemic concentrations of ~0.6μmol/L, all three SNOs reduced mean arterial blood pressure by ~50%, with pronounced vasodilation in the mesenteric bed. Pharmacokinetics of L-cysNO and GSNO were measured in vitro and in vivo and correlated with their hemodynamic effects, membrane permeability, and S-transnitrosylation. These results suggest local vasodilation by SNOs in the hind limb requires membrane permeation, whereas systemic vasodilation does not. The systemic hemodynamic effects of SNOs occur after equilibration of the NO moiety amongst the plasma thiols via S-transnitrosylation.