John R. Halliwill

Influence of the Menstrual Cycle on Sympathetic Activity, Baroreflex Sensitivity, and Vascular Transduction in Young Women

BACKGROUND Our goal was to test sympathetic and cardiovagal baroreflex sensitivity and the transduction of sympathetic traffic into vascular resistance during the early follicular (EF) and midluteal (ML) phases of the menstrual cycle. METHODS AND RESULTS Sympathetic baroreflex sensitivity was assessed by lowering and raising blood pressure with intravenous bolus doses of sodium nitroprusside and phenylephrine. It was defined as the slope relating muscle sympathetic nerve activity (MSNA; determined by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. Vascular transduction was evaluated during ischemic handgrip exercise and postexercise ischemia, and it was defined as the slope relating MSNA and calf vascular resistance (determined by plethysmography). Resting MSNA (EF, 1170+/-151 U/min; ML, 2252+/-251 U/min; P<0.001) and plasma norepinephrine levels (EF, 240+/-21 pg/mL; ML, 294+/-25 pg/mL; P=0. 025) were significantly higher in the ML than in the EF phase. Furthermore, sympathetic baroreflex sensitivity was greater during the ML than the EF phase in every subject (MSNA/diastolic blood pressure slopes: EF, -4.15; FL, -5.42; P=0.005). No significant differences in cardiovagal baroreflex sensitivity or vascular transduction were observed. CONCLUSIONS The present study suggests that the hormonal fluctuations that occur during the normal menstrual cycle may alter sympathetic outflow but not the transduction of sympathetic activity into vascular resistance.

Effect of Various Lithotomy Positions on Lower-extremity Blood Pressure

Background Compartment syndrome of a lower extremity from hypoperfusion is a rare but potentially devastating complication of the lithotomy position during surgery. The aim of this study is to determine the effects of various lithotomy positions on lower‐extremity blood pressures. Methods Blood pressure in eight young, healthy people was studied for 10 lithotomy positions. Blood pressure measurements were taken in both the upper arm (brachial artery) and the lower extremity (dorsalis pedis). The heart‐to‐ankle height gradient in each position was measured, and a predicted lower‐extremity systolic pressure was calculated. The measured and predicted lower‐extremity systolic blood pressures were compared with repeated measures analysis of variance. Results As a group, the mean systolic blood pressures in the lower extremities correlated closely with the predicted values. However, the difference between measured and predicted pressures varied among the 10 positions (P < 0.05). Conclusions Although lower‐extremity systolic blood pressures in the young, healthy volunteers correlated with predicted values, there was an additional reduction in pressure associated with the lithotomy position. This surprising finding suggests that a lengthy procedure necessitating the use of a lithotomy position for only a portion should be planned so the remainder of the procedure can take place before establishing the position or so the position can be changed to an alternative position when it is no longer needed.

Impaired sympathetic vascular regulation in humans after acute dynamic exercise.

1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post‐exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho‐excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (‐29.7 +/‐ 8.8 and ‐25.3 +/‐ 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post‐exercise intercept, 218 +/‐ 38 total integrated activity (heartbeat)‐1; post‐sham intercept, 318 +/‐ 51 total integrated activity (heartbeat)‐1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post‐exercise slope, 0.0031 +/‐ 0.0007 units (total integrated activity)‐1 min; post‐sham slope, 0.0100 +/‐ 0.0033 units (total integrated activity)‐1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post‐exercise hypotension results from both neural and vascular phenomena.

Heat acclimation improves exercise performance

This study examined the impact of heat acclimation on improving exercise performance in cool and hot environments. Twelve trained cyclists performed tests of maximal aerobic power (VO2max), time-trial performance, and lactate threshold, in both cool [13°C, 30% relative humidity (RH)] and hot (38°C, 30% RH) environments before and after a 10-day heat acclimation (∼50% VO2max in 40°C) program. The hot and cool condition VO2max and lactate threshold tests were both preceded by either warm (41°C) water or thermoneutral (34°C) water immersion to induce hyperthermia (0.8-1.0°C) or sustain normothermia, respectively. Eight matched control subjects completed the same exercise tests in the same environments before and after 10 days of identical exercise in a cool (13°C) environment. Heat acclimation increased VO2max by 5% in cool (66.8 ± 2.1 vs. 70.2 ± 2.3 ml·kg(-1)·min(-1), P = 0.004) and by 8% in hot (55.1 ± 2.5 vs. 59.6 ± 2.0 ml·kg(-1)·min(-1), P = 0.007) conditions. Heat acclimation improved time-trial performance by 6% in cool (879.8 ± 48.5 vs. 934.7 ± 50.9 kJ, P = 0.005) and by 8% in hot (718.7 ± 42.3 vs. 776.2 ± 50.9 kJ, P = 0.014) conditions. Heat acclimation increased power output at lactate threshold by 5% in cool (3.88 ± 0.82 vs. 4.09 ± 0.76 W/kg, P = 0.002) and by 5% in hot (3.45 ± 0.80 vs. 3.60 ± 0.79 W/kg, P < 0.001) conditions. Heat acclimation increased plasma volume (6.5 ± 1.5%) and maximal cardiac output in cool and hot conditions (9.1 ± 3.4% and 4.5 ± 4.6%, respectively). The control group had no changes in VO2max, time-trial performance, lactate threshold, or any physiological parameters. These data demonstrate that heat acclimation improves aerobic exercise performance in temperate-cool conditions and provide the scientific basis for employing heat acclimation to augment physical training programs.

‘Non‐hypotensive’ hypovolaemia reduces ascending aortic dimensions in humans.

1. The notion that small, ‘non‐hypotensive’ reductions of effective blood volume alter neither arterial pressure nor arterial baroreceptor activity is pervasive in the experimental literature. We tested two hypotheses: (a) that minute arterial pressure and cardiac autonomic outflow changes during hypovolaemia induced by lower body suction in humans are masked by alterations in breathing, and (b) that evidence for arterial baroreflex engagement might be obtained from measurements of thoracic aorta dimensions. 2. In two studies, responses to graded lower body suction at 0 (control), 5, 10, 15, 20 and 40 mmHg were examined in twelve and ten healthy young men, respectively. In the first, arterial pressure (photoplethysmograph), R‐R interval, and respiratory sinus arrhythmia amplitude (complex demodulation) were measured during uncontrolled and controlled breathing (constant breathing frequency and tidal volume). In the second, cross‐sectional areas of the ascending thoracic aorta were calculated from nuclear magnetic resonance images. 3. Lower body suction with controlled breathing resulted in an increased arterial pulse pressure at mild levels (5‐20 mmHg; ANOVA, P < 0.05) and a decreased arterial pulse pressure at moderate levels (40 mmHg; ANOVA, P < 0.05). Both R‐R intervals and respiratory sinus arrhythmia were negatively related to lower body suction level, whether group averages (general linear regression, r > 0.92) or individual subjects (orthogonal polynomials, 12 of 12 subjects) were assessed. 4. Aortic pulse area decreased progressively and significantly during mild lower body suction, with 47% of the total decline occurring by 5 mmHg. 5. These results suggest that small reductions of effective blood volume reduce aortic baroreceptive areas and trigger haemodynamic adjustments which are so efficient that alterations in arterial pressure escape detection by conventional means.

Forearm sympathetic withdrawal and vasodilatation during mental stress in humans

1 In humans, mental stress elicits vasodilatation in the muscle vascular beds of the forearm that may be neurally mediated. We sought to determine the extent to which this vasodilatation is due to sympathetic withdrawal, active neurogenic vasodilatation, or β‐adrenergically mediated vasodilatation. 2 We simultaneously measured forearm blood flow and muscle sympathetic nerve traffic to the forearm during mental stress in humans. In a second study, we measured forearm blood flow responses to mental stress after selective blockade of α‐adrenergic neurotransmission in one forearm. In a final study, we measured forearm blood flow responses to mental stress after unilateral anaesthetic blockade of the stellate ganglion, alone or in combination with selective β‐adrenergic receptor blockade of the forearm. 3 During mental stress, muscle sympathetic nerve activity decreased from 5113 ± 788 to 1509 ± 494 total integrated activity min− (P < 0.05) and forearm vascular resistance decreased from 96 ± 29 to 33 ± 7 mmHg (dl of tissue) min ml− (P < 0.05). Considerable vasodilatation was still elicited by mental stress after selective blockade of α‐adrenergic neurotransmission. Vasodilatation also occurred during mental stress after stellate ganglion blockade. This dilatation was reduced by selective blockade of β‐adrenergic receptors in the forearm. 4 Our results support a role for both sympathetic withdrawal and β‐adrenergic vasodilatation as the major causes of the forearm vasodilatation during mental stress in humans.

Postexercise hypotension and sustained postexercise vasodilatation: what happens after we exercise?

•  What is the topic for this review? During the exercise recovery period, the combination of centrally mediated decreases in sympathetic nerve activity with a reduced signal transduction from sympathetic nerve activation into vasoconstriction, as well as local vasodilator mechanisms, contributes to the fall in arterial blood pressure seen after exercise. •  What advances does it highlight? Important findings from recent studies include the recognition that skeletal muscle afferents may play a primary role in postexercise resetting of the baroreflex via discrete receptor changes within the nucleus tractus solitarii and that sustained postexercise vasodilatation of the previously active skeletal muscle is primarily the result of histamine H1 and H2 receptor activation.

Effects of regional phentolamine on hypoxic vasodilatation in healthy humans

1 Limb vascular beds exhibit a graded dilatation in response to hypoxia despite increased sympathetic vasoconstrictor nerve activity. We investigated the extent to which sympathetic vasoconstriction can mask hypoxic vasodilatation and assessed the relative contributions of β‐adrenergic and nitric oxide (NO) pathways to hypoxic vasodilatation. 2 We measured forearm blood flow responses (plethysmography) to isocapnic hypoxia (arterial saturation ∼85 %) in eight healthy men and women (18‐26 years) after selective α‐adrenergic blockade (phentolamine) of one forearm. Subsequently, we measured hypoxic responses after combined α‐ and β‐adrenergic blockade (phentolamine and propranolol) and after combined α‐ and β‐adrenergic blockade coupled with NO synthase inhibition (NG‐monomethyl‐l‐arginine, l‐NMMA). 3 Hypoxia increased forearm vascular conductance by 49.0 ± 13.5 % after phentolamine (compared to +16.8 ± 7.0 % in the control arm without phentolamine, P < 0.05). After addition of propranolol, the forearm vascular conductance response to hypoxia was reduced by ∼50 %, but dilatation was still present (+24.7 ± 7.0 %, P < 0.05 vs. normoxia). When l‐NMMA was added, there was no further reduction in the forearm vascular conductance response to hypoxia (+28.2 ± 4.0 %, P < 0.05 vs. normoxia). 4 Thus, selective regional α‐adrenergic blockade unmasked a greater hypoxic vasodilatation than occurs in the presence of functional sympathetic nervous system responses to hypoxia. Furthermore, approximately half of the hypoxic vasodilatation in the forearm appears to be mediated by β‐adrenergic receptor‐mediated pathways. Finally, since considerable dilatation persists in the presence of both β‐adrenergic blockade and NO synthase inhibition, it is likely that an additional vasodilator mechanism is activated by hypoxia in humans.

Exercise and vascular adaptation in asymptomatic humans

Beneficial effects of exercise training on the vasculature have been consistently reported in subjects with cardiovascular risk factors or disease, whereas studies in apparently healthy subjects have been less uniform. In this review, we examine evidence pertaining to the impact of exercise training on conduit and resistance vessel function and structure in asymptomatic subjects. Studies of arterial function in vivo have mainly focused on the endothelial nitric oxide dilator system, which has generally been shown to improve following training. Some evidence suggests that the magnitude of benefit depends upon the intensity or volume of training and the relative impact of exercise on upregulation of dilator pathways versus effects of inflammation and/or oxidation. Favourable effects of training on autonomic balance, baroreflex function and brainstem modulation of sympathetic control have been reported, but there is also evidence that basal vasoconstrictor tone increases as a result of training such that improvements in intrinsic vasodilator function and arterial remodelling are counterbalanced at rest. Studies of compliance suggest increases in both the arterial and the venous sides of the circulation, particularly in older subjects. In terms of mechanisms, shear stress appears to be a key signal to improvement in vascular function, whilst increases in pulse pressure and associated haemodynamics during bouts of exercise may transduce vascular adaptation, even in vascular beds which are distant from the active muscle. Different exercise modalities are associated with idiosyncratic patterns of blood flow and shear stress, and this may have some impact on the magnitude of exercise training effects on arterial function and remodelling. Other studies support the theory that that there may be different time course effects of training on specific vasodilator and constrictor pathways. A new era of understanding of the direct impacts of exercise and training on the vasculature is evolving, and future studies will benefit greatly from technological advances which allow direct characterization of arterial function and structure.

Sympathetic Activity and Baroreflex Sensitivity in Young Women Taking Oral Contraceptives

BackgroundWe tested sympathetic and cardiovagal baroreflex sensitivity during the placebo or “low-hormone” phase (LH) and 2 to 3 weeks later during the “high-hormone” phase (HH) of oral contraceptive (OC) use in 9 women. Methods and ResultsSympathetic baroreflex sensitivity was assessed by intravenous doses of sodium nitroprusside and phenylephrine and defined as the slope relating muscle sympathetic nerve activity (by microneurography) and diastolic blood pressure. Cardiovagal baroreflex sensitivity was defined as the slope relating R-R interval and systolic blood pressure. No difference was observed for resting muscle sympathetic nerve activity or plasma norepinephrine levels. However, sympathetic baroreflex sensitivity was greater and mean arterial pressure was higher during the LH than in the HH phase. Similarly, cardiovagal baroreflex sensitivity was greater in the LH than in the HH phase. ConclusionsSympathetic and cardiovagal baroreflex sensitivities change during the 28-day course of OC use. Furthermore, changes in baroreflex sensitivity with OC differ from changes in baroreflex sensitivity during the normal menstrual cycle.