Human baroreflex rhythms persist during handgrip and muscle ischaemia.

AIM: To determine whether physiological, rhythmic fluctuations of vagal baroreflex gain persist during exercise, post-exercise ischaemia and recovery. METHODS: We studied responses of six supine healthy men and one woman to a stereotyped protocol comprising rest, handgrip exercise at 40% maximum capacity to exhaustion, post-exercise forearm ischaemia and recovery. We measured electrocardiographic R-R intervals, photoplethysmographic finger arterial pressures and peroneal nerve muscle sympathetic activity. We derived vagal baroreflex gains from a sliding (25-s window moved by 2-s steps) systolic pressure-R-R interval transfer function at 0.04-0.15 Hz. RESULTS: Vagal baroreflex gain oscillated at low, nearly constant frequencies throughout the protocol (at approx. 0.06 Hz - a period of about 18 s); however, during exercise, most oscillations were at low-gain levels, and during ischaemia and recovery, most oscillations were at high-gain levels. CONCLUSIONS: Vagal baroreflex rhythms are not abolished by exercise, and they are not overwhelmed after exercise during ischaemia and recovery.

A somatostatin analog improves tilt table tolerance by decreasing splanchnic vascular conductance.

Splanchnic hemodynamics and tilt table tolerance were assessed after an infusion of placebo or octreotide acetate, a somatostatin analog whose vascular effects are largely confined to the splanchnic circulation. We hypothesized that reductions in splanchnic blood flow (SpBF) and splanchnic vascular conductance (SpVC) would be related to improvements in tilt table tolerance. In randomized, double-blind, crossover trials, hemodynamic variables were collected in 14 women and 16 men during baseline, 70° head-up tilt (HUT), and recovery. A repeated-measures analysis of variance was used to compare changes from baseline with respect to sex and condition. HUT elicited an increase in heart rate and decreases in mean arterial pressure, cardiac index, stroke index, and systemic vascular conductance. Additionally, SpVC and non-SpVC were lower during HUT. Octreotide reduced SpBF and SpVC and increased systemic vascular conductance and non-SpVC. Changes in SpBF and SpVC between supine and HUT were smaller in women (P < 0.05). Tilt table tolerance was increased after administration of octreotide [median tilt time: 15.7 vs. 37.0 min (P < 0.05) and 21.8 vs. 45.0 min (P < 0.05) for women and men, respectively]. A significant relationship existed between change (Δ) in SpBF (placebo-octreotide) and Δtilt time in women (Δtilt time = 2.5-0.0083 ΔSpBF, P < 0.01), but not men (Δtilt time = 3.41-0.0008 ΔSpBF, P = 0.59). In conclusion, administration of octreotide acetate improved tilt table tolerance, which was associated with a decrease in SpVC. In women, but not men, the magnitude of reduction in SpBF was positively associated with improvements in tilt tolerance.

Sex differences in vasoconstrictor reserve during 70 deg head-up tilt.

Women are generally recognized to be less orthostatically tolerant than men. We hypothesized that during head-up tilt (HUT), women would demonstrate less splanchnic vasoconstriction, leading to splanchnic pooling, lower blood pressure and lower orthostatic tolerance. Mean arterial blood pressure (MAP), heart rate (HR), cardiac output ((.)Q(c), assessed by C2H2 rebreathing), stroke volume, splanchnic blood flow (SpBF, assessed by Indocyanine Green clearance) and vascular conductance (systemic, SVC = (.)Qc/MAP; splanchnic, SpVC = SpBF/MAP; non-splanchnic, non-SpVC = SVC - SpVC) were measured during supine baseline conditions, 70 deg HUT and recovery in 14 healthy women (23 +/- 6 years old; mean +/- S.D.) and 16 men (23 +/- 5 years old). The proportion of sexes surviving 45 min of HUT trended towards significance (chi(2) = 2.92, P = 0.09). The MAP was lower in women than in men (supine, 77 +/- 5 versus 86 +/- 9 mmHg, P < 0.01; tilt, 72 +/- 8 versus 83 +/- 10 mmHg, P < 0.01), while HR and cardiac index ( /body surface area) were not different between the sexes (heart rate supine, 66 +/- 6 versus 64 +/- 8 beats min(-1); heart rate tilt, 96 +/- 13 versus 94 +/- 10 beats min(-1); cardiac index supine, 3.8 +/- 0.9 versus 3.7 +/- 0.7 l min(-1) m(2); cardiac index tilt, 2.7 +/- 0.8 versus 2.3 +/- 0.5 l min(-1) m(2)). The SpBF and SpVC were lower in women at rest but not during tilt (SpBF supine, 1174 +/- 243 versus 1670 +/- 391 ml min(-1), P < 0.01; SpVC supine, 14.83 +/- 3.61 versus 19.59 +/- 4.95 ml min(-1) mmHg(1), P < 0.01; SpBF tilt, 884 +/- 300 versus 1094 +/- 271 ml min(-1); SpVC tilt, 13.14 +/- 4.28 versus 14.82 +/- 4.16 ml min(-1) mmHg(-1)). However, in the women the SpVC did not decrease from baseline to tilt (SpVC, in women, 1.70 +/- 3.19 ml min(-1) mmHg(-1), n.s.; in men, 4.81 +/- 3.44 ml min(-1) mmHg(-1), P < 0.01), suggesting a blunted vasoconstrictor response. In conclusion, women tended to have lower tilt-table tolerance associated with a smaller splanchnic vasoconstrictor reserve than men.

Simultaneous determination of the accuracy and precision of closed-circuit cardiac output rebreathing techniques.

Foreign and soluble gas rebreathing methods are attractive for determining cardiac output (Q(c)) because they incur less risk than traditional invasive methods such as direct Fick and thermodilution. We compared simultaneously obtained Q(c) measurements during rest and exercise to assess the accuracy and precision of several rebreathing methods. Q(c) measurements were obtained during rest (supine and standing) and stationary cycling (submaximal and maximal) in 13 men and 1 woman (age: 24 +/- 7 yr; height: 178 +/- 5 cm; weight: 78 +/- 13 kg; Vo(2max): 45.1 +/- 9.4 ml.kg(-1).min(-1); mean +/- SD) using one-N(2)O, four-C(2)H(2), one-CO(2) (single-step) rebreathing technique, and two criterion methods (direct Fick and thermodilution). CO(2) rebreathing overestimated Q(c) compared with the criterion methods (supine: 8.1 +/- 2.0 vs. 6.4 +/- 1.6 and 7.2 +/- 1.2 l/min, respectively; maximal exercise: 27.0 +/- 6.0 vs. 24.0 +/- 3.9 and 23.3 +/- 3.8 l/min). C(2)H(2) and N(2)O rebreathing techniques tended to underestimate Q(c) (range: 6.6-7.3 l/min for supine rest; range: 16.0-19.1 l/min for maximal exercise). Bartlett's test indicated variance heterogeneity among the methods (P < 0.05), where CO(2) rebreathing consistently demonstrated larger variance. At rest, most means from the noninvasive techniques were +/-10% of direct Fick and thermodilution. During exercise, all methods fell outside the +/-10% range, except for CO(2) rebreathing. Thus the CO(2) rebreathing method was accurate over a wider range (rest through maximal exercise), but was less precise. We conclude that foreign gas rebreathing can provide reasonable Q(c) estimates with fewer repeat trials during resting conditions. During exercise, these methods remain precise but tend to underestimate Q(c). Single-step CO(2) rebreathing may be successfully employed over a wider range but with more measurements needed to overcome the larger variability.

Effects of 18 days of bed rest on leg and arm venous properties.

Venous function may be altered by bed rest deconditioning. Yet the contribution of altered venous compliance to the orthostatic intolerance observed after bed rest is uncertain. The purpose of this study was to assess the effect of 18 days of bed rest on leg and arm (respectively large and small change in gravitational gradients and use patterns) venous properties. We hypothesized that the magnitude of these venous changes would be related to orthostatic intolerance. Eleven healthy subjects (10 men, 1 woman) participated in the study. Before (pre) and after (post) 18 days of 6 degrees head-down tilt bed rest, strain gauge venous occlusion plethysmography was used to assess limb venous vascular characteristics. Leg venous compliance was significantly decreased after bed rest (pre: 0.048 +/- 0.007 ml x 100 ml(-1) x mmHg(-1), post: 0.033 +/- 0.007 ml x 100 ml(-1) x mmHg(-1); P < 0.01), whereas arm compliance did not change. Leg venous flow resistance increased significantly after bed rest (pre: 1.73 +/- 1.08 mmHg x ml(-1) x 100 ml x min, post: 3.10 +/- 1.00 mmHg x ml(-1) x 100 ml x min; P < 0.05). Maximal lower body negative pressure tolerance, which was expressed as cumulative stress index (pressure x time), decreased in all subjects after bed rest (pre: 932 mmHg x min, post: 747 mmHg x min). The decrease in orthostatic tolerance was not related to changes in leg venous compliance. In conclusion, this study demonstrates that after bed rest, leg venous compliance is reduced and leg venous outflow resistance is enhanced. However, these changes are not related to measures of orthostatic tolerance; therefore, alterations in venous compliance do not to play a major role in orthostatic intolerance after 18 days of head-down tilt bed rest.

Regulation of muscle sympathetic nerve activity after bed rest deconditioning.

Cardiovascular deconditioning reduces orthostatic tolerance. To determine whether changes in autonomic function might produce this effect, we developed stimulus-response curves relating limb vascular resistance, muscle sympathetic nerve activity (MSNA), and pulmonary capillary wedge pressure (PCWP) with seven subjects before and after 18 days of -6 degrees head-down bed rest. Both lower body negative pressure (LBNP; -15 and -30 mmHg) and rapid saline infusion (15 and 30 ml/kg body wt) were used to produce a wide variation in PCWP. Orthostatic tolerance was assessed with graded LBNP to presyncope. Bed rest reduced LBNP tolerance from 23.9 +/- 2.1 to 21.2 +/- 1.5 min, respectively (means +/- SE, P = 0.02). The MSNA-PCWP relationship was unchanged after bed rest, though at any stage of the LBNP protocol PCWP was lower, and MSNA was greater. Thus bed rest deconditioning produced hypovolemia, causing a shift in operating point on the stimulus-response curve. The relationship between limb vascular resistance and MSNA was not significantly altered after bed rest. We conclude that bed rest deconditioning does not alter reflex control of MSNA, but may produce orthostatic intolerance through a combination of hypovolemia and cardiac atrophy.

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure.

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this "deconditioning response" could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of -6 degrees head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15-0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate x stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05-0.15 Hz) power of systolic BP variability decreased after bed rest (-22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

Age, splanchnic vasoconstriction, and heat stress during tilting.

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

Age alters the cardiovascular response to direct passive heating.

During direct passive heating in young men, a dramatic increase in skin blood flow is achieved by a rise in cardiac output (Qc) and redistribution of flow from the splanchnic and renal vascular beds. To examine the effect of age on these responses, seven young (Y; 23 +/- 1 yr) and seven older (O; 70 +/- 3 yr) men were passively heated with water-perfused suits to their individual limit of thermal tolerance. Measurements included heart rate (HR), Qc (by acetylene rebreathing), central venous pressure (via peripherally inserted central catheter), blood pressures (by brachial auscultation), skin blood flow (from increases in forearm blood flow by venous occlusion plethysmography), splanchnic blood flow (by indocyanine green clearance), renal blood flow (by p-aminohippurate clearance), and esophageal and mean skin temperatures. Qc was significantly lower in the older than in the young men (11.1 +/- 0.7 and 7.4 +/- 0.2 l/min in Y and O, respectively, at the limit of thermal tolerance; P < 0. 05), despite similar increases in esophageal and mean skin temperatures and time to reach the limit of thermal tolerance. A lower stroke volume (99 +/- 7 and 68 +/- 4 ml/beat in Y and O, respectively, P < 0.05), most likely due to an attenuated increase in inotropic function during heating, was the primary factor for the lower Qc observed in the older men. Increases in HR were similar in the young and older men; however, when expressed as a percentage of maximal HR, the older men relied on a greater proportion of their chronotropic reserve to obtain the same HR response (62 +/- 3 and 75 +/- 4% maximal HR in Y and O, respectively, P < 0.05). Furthermore, the older men redistributed less blood flow from the combined splanchnic and renal circulations at the limit of thermal tolerance (960 +/- 80 and 720 +/- 100 ml/min in Y and O, respectively, P < 0. 05). As a result of these combined attenuated responses, the older men had a significantly lower increase in total blood flow directed to the skin.

Cardiac atrophy after bed-rest deconditioning: a nonneural mechanism for orthostatic intolerance.

BACKGROUND: The cardiovascular adaptation to bed rest leads to orthostatic intolerance, characterized by an excessive fall in stroke volume (SV) in the upright position. We hypothesized that this large fall in SV is due to a change in cardiac mechanics. METHODS AND RESULTS: We measured pulmonary capillary wedge pressure (PCWP), SV, left ventricular end-diastolic volume (LVEDV), and left ventricular mass (by echocardiography) at rest, during lower-body negative pressure, and after saline infusion before and after 2 weeks of bed rest with -6 degrees head-down tilt (n=12 subjects aged 24+/-5 years). Pressure (P)-volume (V) curves were modeled exponentially by P=ae(kV)+b and logarithmically by P=-Sln[(Vm-V)/(Vm-V0)], where V0 indicates volume at P=0, and the constants k and S were used as indices of normalized chamber stiffness. Dynamic stiffness (dP/dV) was calculated at baseline LVEDV. The slope of the line relating SV to PCWP during lower-body negative pressure characterized the steepness of the Starling curve. We also measured plasma volume (with Evans blue dye) and maximal orthostatic tolerance. Bed rest led to a reduction in plasma volume (17%), baseline PCWP (18%), SV (12%), LVEDV (16%), V0 (33%), and orthostatic tolerance (24%) (all P<.05). The slope of the SV/PCWP curve increased from 4.6+/-0.4 to 8.8+/-0.9 mL/mm Hg (P<.01) owing to a parallel leftward shift in the P-V curve. Normalized chamber stiffness was unchanged, but dP/dV was reduced by 50% at baseline LVEDV, and cardiac mass tended to be reduced by 5% (P<.10). CONCLUSIONS: Two weeks of head-down-tilt bed rest leads to a smaller, less distensible left ventricle but a shift to a more compliant portion of the P-V curve. This results in a steeper Starling relationship, which contributes to orthostatic intolerance by causing an excessive reduction in SV during orthostasis.

Cardiovascular and catecholamine responses to static exercise in partially curarized humans.

Neural control of the circulation was evaluated during static exercise in 19 subjects by the determination of heart rate (HR), mean arterial pressure (MAP), cardiac output (CO) and plasma catecholamines. Influence from central command was evaluated during contractions with weakened muscles following partial curarization and reflex influence from metaboreceptors was assessed by post-exercise muscle ischaemia. Static handgrip increased HR and more so MAP and CO and MAP remained elevated during post-exercise muscle ischaemia. With partial curarization plasma catecholamines were also increased (P < 0.05). Two-leg extension increased all variables and during post-exercise muscle ischaemia elevations of HR, MAP and CO were maintained (P < 0.05). With partial curarization HR, MAP and plasma noradrenaline were even greater during the contraction. With the involvement of both legs during static exercise, reflex influence from the muscles elevated blood pressure by way of HR and CO and the importance of central command was detectable for HR and MAP as plasma catecholamines became elevated. However, the results indicate a separation between a central command influence on HR and CO related to an increase in plasma catecholamines during a handgrip, while the reflex influence on blood pressure was directed towards total peripheral resistance.

Effects of head-down-tilt bed rest on cerebral hemodynamics during orthostatic stress.

Our aim was to determine whether the adaptation to simulated microgravity (microG) impairs regulation of cerebral blood flow (CBF) during orthostatic stress and contributes to orthostatic intolerance. Twelve healthy subjects (aged 24 +/- 5 yr) underwent 2 wk of -6 degrees head-down-tilt (HDT) bed rest to simulate hemodynamic changes that occur when humans are exposed to microG. CBF velocity in the middle cerebral artery (transcranial Doppler), blood pressure, cardiac output (acetylene rebreathing), and forearm blood flow were measured at each level of a ramped protocol of lower body negative pressure (LBNP; -15, -30, and -40 mmHg x 5 min, -50 mmHg x 3 min, then -10 mmHg every 3 min to presyncope) before and after bed rest. Orthostatic tolerance was assessed by using the cumulative stress index (CSI; mmHg x minutes) for the LBNP protocol. After bed rest, each individual's orthostatic tolerance was reduced, with the group CSI decreased by 24% associated with greater decreases in cardiac output and greater increases in systemic vascular resistance at each level of LBNP. Before bed rest, mean CBF velocity decreased by 14, 10, and 45% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. After bed rest, mean velocity decreased by 16% at -30 mmHg and by 21, 35, and 39% at -40 mmHg, -50 mmHg, and maximal LBNP, respectively. Compared with pre-bed rest, post-bed-rest mean velocity was less by 11, 10, and 21% at -30, -40, and -50 mmHg, respectively. However, there was no significant difference at maximal LBNP. We conclude that cerebral autoregulation during orthostatic stress is impaired by adaptation to simulated microG as evidenced by an earlier and greater fall in CBF velocity during LBNP. We speculate that impairment of cerebral autoregulation may contribute to the reduced orthostatic tolerance after bed rest.

Divergence of ventilatory responses to isometric contraction in anesthetized cats.

The purpose of this study was to determine if the initial ventilatory and phrenic nerve responses to isometric contraction of the triceps surae muscle of anesthetized cats are influenced by the pattern of the contraction. To address this, three different types of muscle contraction were evoked: (1) a high tension, continuous tetanic (HT-CT) contraction; (2) a moderate tension, continuous tetanic (MT-CT) contraction; and (3) high tension, intermittent tetanic (HT-IT) contractions. The duration of each contraction period was 60 sec. The MT-CT and HT-IT contractions increased minute volume (VE; 19 +/- 4% and 15 +/- 5%, respectively) within the first 15 sec. These increases were the result of rises in breathing frequency and tidal volume. However, only the MT-CT contraction increased phrenic activity (pVE) in the first 15 sec. By contrast, ventilation and phrenic nerve activity failed to increase within the first 15 sec of the HT-CT contraction. If fact, 'tidal' phrenic activity (pVT; -14 +/- 5%) decreased during the first 5 sec, and there was a tendency for tidal volume (VT; -8 +/- 5%), VE (-8 +/- 6%), and pVE (-16 +/- 8%) to fall. These data suggest that stimulation of muscle afferent fibers by static contraction can initially inhibit phrenic nerve activity, provided the activation is sustained and of sufficient intensity.

Effect of skeletal muscle fiber type on the pressor response evoked by static contraction in rabbits.

The purpose of this study was to determine whether the reflex hemodynamic responses to static contraction of predominately glycolytic muscle are greater than the changes elicited by primarily oxidative muscle. Low-frequency electrical stimulation (continuous 21 days) of the tibial nerve of one hindlimb of adult rabbits converted the metabolic characteristics of the predominately glycolytic gastrocnemius to a muscle that was primarily oxidative. After 21 days of stimulation, the rabbits were decerebrated, and static contraction of the glycolytic muscle (unstimulated gastrocnemius) initially decreased heart rate (HR; -16 +/- 3 beats/min) and mean arterial pressure (MAP; -17 +/- 3 mmHg). Thereafter, MAP increased 13 +/- 3 mmHg above baseline. Static contraction of the oxidative muscle (stimulated gastrocnemius) produced similar decreases in HR and MAP (-12 +/- 4 beats/min and -12 +/- 3 mmHg, respectively). However, the subsequent increase in MAP (8 +/- 3 mmHg; above baseline) was less than that evoked by contraction of the glycolytic muscle. The responses evoked by stretch of each muscle and high-intensity electrical stimulation were the same, indicating that the afferents from the muscle were not destroyed by the chronic-stimulation technique. These results support the hypothesis that metabolic by-products play a role in the pressor response to static contraction of skeletal muscle. In addition, these data confirm that contraction of predominately oxidative muscle can evoke a reflex pressor response, albeit smaller than the change elicited from primarily glycolytic muscle.

Power spectral and time based analysis of heart rate variability following 15 days head-down bed rest.

Power spectral and time based analyses were applied to the cardiac inter-beat interval (RRI) of 8 healthy men before and after 15 d of bed rest in the 6 degrees head-down tilt position (HDT) to determine changes in indices of cardiac parasympathetic and sympathetic activity after this exposure. At 24 h prior to HDT and on HDT day 15, a minimum of 256 RRI's were obtained from an electrocardiogram (ECG) while the subjects were in the supine position. RRI was subjected to power spectral and two methods of time-based analyses. Power spectral analysis demonstrated that the index of cardiac vagal activity was reduced (95.2 +/- 28.5 to 48.2 +/- 17.4 ms2) without affecting the index of cardiac sympathetic activity (1.18 +/- 0.7 to 0.69 +/- 0.4). The two methods of time-based analyses, time series and standard deviation analyses, further demonstrated a reduction of cardiac vagal activity post-HDT (5.5 +/- 4 to 4.8 +/- 0.6 ms2; and 42.8 +/- 4.8 to 33.9 +/- 3.3 ms, respectively). These data suggest that exposure to 15 d of HDT reduces cardiac vagal activity, while changes in cardiac sympathetic activity were indistinguishable.

Cardiovascular and renal nerve responses to static muscle contraction of decerebrate rabbits.

The purpose of this study was to determine whether the biphasic arterial blood pressure responses elicited by static muscle contraction of decerebrate rabbits are mediated, at least in part, by an initial decrease and a subsequent increase in sympathetic outflow. Renal sympathetic nerve activity (RSNA) was used as an index of sympathetic outflow. Static contraction of the triceps surae muscle (n = 14) initially decreased mean arterial blood pressure (MAP) -20 +/- 3 mmHg and heart rate (HR) -15 +/- 5 beats/min (nadir values). After this initial decrease, MAP increased 12 +/- 2 mmHg (peak increase) above baseline and there was a tendency for HR to be elevated (6 +/- 3 beats/min). The changes in RSNA during muscle contraction (n = 6) mirrored the nadir and peak responses of MAP (-50 +/- 9 and 32 +/- 11%). Muscle stretch (n = 11) also evoked similar nadir and peak responses of MAP (-20 +/- 5 and 9 +/- 1 mmHg), HR (-17 +/- 7 and 3 +/- 3 beats/min), and RSNA (-43 +/- 9 and 46 +/- 15%). These data suggest that the initial depressor and subsequent pressor responses elicited by skeletal muscle contraction and stretch are mediated, at least in part, by biphasic changes in sympathetic outflow.

Cardiorespiratory and phrenic nerve responses to graded muscle stretch in anesthetized cats.

This study examined the cardiovascular, ventilatory, and phrenic nerve responses to graded activation of mechanically sensitive muscle afferents. Using eight alpha-chloralose anesthetized cats, the left and right triceps surae muscles were stretched individually and simultaneously at progressive increments (0.5, 1.0, 1.5, 1.75 cm). Muscle stretch elicited sustained increases in mean arterial blood pressure (MAP) and heart rate (HR). These changes were related to the degree of stretch, as stretching one muscle 0.5 cm increased MAP 15 +/- 2 mmHg and HR 7 +/- 2 beats/min, while stretching both legs (1.75 cm) increases these variables 40 +/- 11 mmHg and 11 +/- 3 beats/min. By contrast, muscle stretch initially decreased ventilation and phrenic nerve activity. After the initial fall, ventilation, but not tidal phrenic activity, increased above baseline. These results show that a divergence exists between the initial cardiovascular and ventilatory responses to activation of mechanically sensitive muscle afferents. Further, the hyperpnea elicited by muscle stretch in spontaneously breathing anesthetized cats appears to be the result of excitation of non-diaphragmatic muscles of ventilation.

Naloxone does not affect the cardiovascular and sympathetic adjustments to static exercise in humans.

Previous studies suggested that endogenous opiates may attenuate the cardiovascular and sympathetic adjustments to static exercise. We tested whether this effect originates from exercising skeletal muscle. Eight men performed 2 min of static handgrip (30% maximum) followed by 2 min of posthandgrip muscle ischemia after three interventions: 1) control, 2) intra-arterial injection of naloxone HCl (60 micrograms) or vehicle (saline) in the exercising arm, and 3) systemic infusion of naloxone (4 mg) or vehicle. Naloxone and vehicle trials were performed double blind on separate days. Preexercise baseline muscle sympathetic nerve activity (burst frequency), heart rate, and blood pressure were similar across interventions on either day. During static handgrip, control, intra-arterial, and systemic administration of vehicle and naloxone elicited similar increases in total muscle sympathetic nerve activity (58 +/- 24 vs. 68 +/- 26, 146 +/- 49 vs. 132 +/- 42, 137 +/- 54 vs. 164 +/- 44%, respectively), heart rate (9 +/- 2 vs. 8 +/- 3, 16 +/- 3 vs. 16 +/- 2, 20 +/- 4 vs. 19 +/- 3 beats/min, respectively), and mean arterial pressure (22 +/- 4 vs. 21 +/- 4, 29 +/- 5 vs. 26 +/- 3, 28 +/- 4 vs. 27 +/- 4 mmHg, respectively). Additionally, there were no differences between vehicle and naloxone trials during posthandgrip muscle ischemia. Thus, contrary to previous reports, we conclude that the endogenous opiate peptide system does not modulate cardiovascular and sympathetic responses to brief periods of static exercise or muscle ischemia in humans.

Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.

BACKGROUND: During static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms. METHODS AND RESULTS: Thirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute. Heart rate, blood pressure, and cardiac output were measured and stroke volume and systemic vascular resistance were calculated at rest and at 1 and 5 minutes during static one-leg extension at 20% of maximal voluntary contraction. The mean arterial pressures at rest and at 5 minutes were higher when the heart rate was fixed at the faster peak exercise heart rate. In the DDD mode, heart rate increased by 16 beats per minute and cardiac output by 1.1 L/min, with a resultant 25 mm Hg increase in mean arterial pressure at 5 minutes with no change in the stroke volume or systemic vascular resistance. In both fixed heart rate pacing modes, mean arterial pressure increased by 24 mm Hg when the heart rate was fixed at the resting heart rate and by 25 mm Hg when the heart rate was fixed at the faster peak exercise heart rate pacing modes associated with an increase in stroke volume, with similar increases in cardiac output. During static exercise there was no change in systemic vascular resistance from the resting value in any pacing mode. CONCLUSIONS: When heart rate is fixed in the presence of normal left ventricular function, the mean arterial pressure increases normally during static exercise because of an increase in stroke volume with no change in the systemic vascular resistance.

Neural control of cardiovascular responses and of ventilation during dynamic exercise in man.

1. Nine subjects performed dynamic knee extension by voluntary muscle contractions and by evoked contractions with and without epidural anaesthesia. Four exercise bouts of 10 min each were performed: three of one-legged knee extension (10, 20 and 30 W) and one of two-legged knee extension at 2 x 20 W. Epidural anaesthesia was induced with 0.5% bupivacaine or 2% lidocaine. Presence of neural blockade was verified by cutaneous sensory anaesthesia below T8-T10 and complete paralysis of both legs. 2. Compared to voluntary exercise, control electrically induced exercise resulted in normal or enhanced cardiovascular, metabolic and ventilatory responses. However, during epidural anaesthesia the increase in blood pressure with exercise was abolished. Furthermore, the increases in heart rate, cardiac output and leg blood flow were reduced. In contrast, plasma catecholamines, leg glucose uptake and leg lactate release, arterial carbon dioxide tension and pulmonary ventilation were not affected. Arterial and venous plasma potassium concentrations became elevated but leg potassium release was not increased. 3. The results conform to the idea that a reflex originating in contracting muscle is essential for the normal blood pressure response to dynamic exercise, and that other neural, humoral and haemodynamic mechanisms cannot govern this response. However, control mechanisms other than central command and the exercise pressor reflex can influence heart rate, cardiac output, muscle blood flow and ventilation during dynamic exercise in man.