Does venous insufficiency impair the exercise-induced rise in arterial leg blood flow?

OBJECTIVES: It has been shown that the leg muscle pump increases the immediate rise in arterial leg blood flow during upright exercise in healthy subjects. The present study is the first to investigate the muscle pump effect in exercise hyperaemia in patients with venous insufficiency, who should be lacking an optimally functioning muscle pump. METHODS: Any muscle pump effect is more pronounced in an upright position because of gravitation. The exercise-induced rise in femoral artery flow (FF) (ultrasound Doppler) was thus compared in the supine and 30° head-up tilted position in 10 patients. RESULTS: Neither the transient nor the steady-state rise in FF showed any difference between positions. This is in contrast to the previous findings in healthy subjects, where the transient rise in FF was larger in the tilted position. CONCLUSION: The muscle pump effect in exercise hyperaemia seems to be reduced or lacking in these patients.

Does the great saphenous vein stripping improve arterial leg blood flow during exercise?

OBJECTIVES: It has been shown that the leg muscle pump increases arterial leg blood flow during upright exercise in healthy subjects, and that this effect is reduced in patients with incompetence of the great saphenous vein (GSV). In this study, patients with GSV reflux causing varicose veins were investigated after GSV stripping, to see whether the muscle pump effect on arterial leg blood flow is improved. DESIGN: Prospective case study. METHODS: Nine patients with GSV incompetence resulting in symptomatic varicose veins, but without peripheral artery disease were included in this study. Patients exercised in the supine and 30° head up tilted positions by rhythmically pressing down a pedal with one foot. Blood flow was measured in the femoral artery using Doppler ultrasound. The Exercise-induced rise in femoral artery blood flow was compared in the supine and 30° head up tilted positions. Patients were investigated both before and after undergoing saphenofemoral ligation and GSV stripping as a treatment for their varicose veins. The arterial blood flow response to exercise was compared between the pre and postoperative observations. RESULTS: Prior to GSV stripping the immediate rise in femoral flow was 0.25 l min(-1) above rest in both supine and tilted positions. After GSV stripping however, the rise in flow was 30% larger in the tilted position than in the supine position (0.26 vs. 0.20 l min(-1), P < 0.05). CONCLUSIONS: GSV stripping modestly improves arterial leg blood flow at the onset of exercise in patients with GSV insufficiency, because of an improved effect of the leg muscle pump.

Role of mechanical factors in governing muscle blood flow.

This study evaluates how mechanical factors impact cardiac output at the systemic level, and how mechanical factors influence muscle blood flow at the local level. Importantly, the two are intertwined; events that work locally in the periphery to augment muscle blood flow can also act centrally to contribute to the development of a high cardiac output.

Does limb angular motion raise limb arterial pressure?

AIM: Mechanical factors such as the muscle pump have been proposed to augment flow by several mechanisms. The potential for limb angular motion to augment local perfusion pressure (pressure = (1/2)rhor(2)omega(2), where rho is the fluid density, r the radius and omega the angular velocity) has been overlooked. We sought to test the hypothesis that limb angular motion augments limb arterial pressure. METHODS: Nine human subjects performed horizontal shoulder flexion ( approximately +/-90 degrees at 0.75 Hz for 30 s). We measured finger arterial pressure (photoplethysmography) in the moving (Trial 1) and non-moving arm (Trial 2) in separate trials along with the pressure (strain gauge) generated at the fingers within a length of water-filled tubing mounted on the moving arm in both trials. RESULTS: Arm swinging raised (P < 0.05) the mean pressure measured in the tubing by 11 +/- 2 and 14 +/- 2 mmHg (Trials 1 and 2 respectively). In response to exercise, the rise in mean finger arterial pressure in the swinging limb (18 +/- 3 mmHg, Trial 1) exceeded (P < 0.05) the rise in the resting limb (8 +/- 2 mmHg, Trial 2) by an amount similar to the 11 mmHg rise in pressure generated in the tubing in Trial 1. CONCLUSIONS: We conclude that the swinging of a limb creates centrifugal force (a biomechanical centrifuge) which imparts additional pressure to the arteries, but not the veins owing to the venous valves, which further widens the arterial-venous pressure difference.

Role of speed vs. grade in relation to muscle pump function at locomotion onset.

We sought to clarify the roles of contraction frequency (speed) and contraction force (grade) in the rise in muscle blood flow at the onset of locomotion. Shoemaker et al. (Can J Physiol Pharmacol 76: 418-427, 1998) explored this relationship in human handgrip exercise and found that the time course of the rise in muscle vascular conductance was similar when a light weight was lifted in a fast cadence and a heavy weight was lifted in a slow cadence (total work constant). This indicates that muscle pumping (contraction frequency) was of limited importance in governing the time course. Rather, vasodilator substances released in proportion to the total work performed appeared to determine the pattern and extent of the rise in conductance. We hypothesized that conductance would rise faster during locomotion at a high speed (frequency) and low grade (force) than at a low speed and high grade, despite similar total increases in conductance, owing to more effective muscle pumping at faster contraction rates. Seven male rats performed nine 1-min bouts of treadmill locomotion across a combination of three speeds (5, 10, and 20 m/min) and three grades (-10, 0, and +15 degrees ) in random order. Locomotion at 10 m/min and 0 degrees grade and 20 m/min and -10 degrees grade led to an equal rise in terminal aortic vascular conductance. However, the equal rise was achieved more quickly at the higher running speed, suggestive of more effective muscle pumping. Across the nine combinations of exercise, speed began to exert a statistically significant influence on conductance by the 3rd s of locomotion. Grade did not begin to exert an influence until the 12th s of locomotion (similar to the delays reported for arteriolar dilation to muscle contraction). Additional experiments in dogs provided similar results. Thus the muscle pump appears to initiate the increase in blood flow in proportion to contraction frequency at locomotion onset.

Brief exposure to -Gz reduces cerebral perfusion pressure during subsequent +Gz stress in rats.

INTRODUCTION: In humans, +Gz exposure immediately preceded by exposure to zero or -Gz can result in unexpected incapacitation ("push-pull" effect). Our goals were to establish whether this phenomenon exists in rats and to evaluate the importance of varying the duration of -Gz exposure on magnitude of the push-pull effect on cerebral perfusion pressure. METHODS: Eight conscious male rats were studied in the transition from +5 Gz to +10 Gz imposed by centrifugation. This was done with (push-pull) or without (control) 2 s exposure to -5 Gz applied using a counterbalanced design. Seven isoflurane anesthetized rats were studied in the transition from 0Gz (+1Gy) to + 1Gz imposed by tilting. This was done with (push-pull) or without (control) 0.5, 1, 3, or 9 s exposure to -1Gz imposed immediately prior to the transition applied using a counterbalanced designed. RESULTS: Exposure to 2 s of -5 Gz significantly (p < 0.01) reduced carotid artery pressure in the 4th through 8th s of exposure to +10 Gz by an average of 15 mmHg compared with control. In the tilt experiments, a push-pull effect was found with mild Gz exposure (+/-1Gz) with as little as 0.5 s -Gz exposure. Varying the head-down dwell time did not alter the magnitude of the exaggerated hypotension induced by "push-pull" (p = 0.90). CONCLUSIONS: We conclude that rats express a "push-pull" effect similar to that observed in humans but that altering the duration of exposure to -Gz does not influence the magnitude of the "push-pull" effect.

Effects of inertial load and countermeasures on the distribution of pulmonary blood flow.

We assessed the influence of cranial-to-caudal inertial force (+G(z)) and the countermeasures of anti-G suit and positive pressure breathing during G (PBG), specifically during +G(z), on regional pulmonary blood flow distribution. Unanesthetized swine were exposed randomly to 0 G(z) (resting), +3 G(z), +6 G(z), and +9 G(z), with and without anti-G suit and PBG with the use of the Air Force Research Laboratory centrifuge at Brooks Air Force Base (the gravitational force of the Earth, that is, the dorsal-to-ventral inertial force, was present for all runs). Fluorescent microspheres were injected into the pulmonary vasculature as a marker of regional pulmonary blood flow. Lungs were excised, dried, and diced into approximately 2-cm(3) pieces, and the fluorescence of each piece was measured. As +G(z) was increased from 0 to +3 G(z), blood flow shifted from cranial and hilar regions toward caudal and peripheral regions of the lung. This redistribution shifted back toward cranial and hilar regions as anti-G suit inflation pressure increased at +6 and +9 G(z). Perfusion heterogeneity increased with +G(z) stress and decreased at the higher anti-G suit pressures. The distribution of pulmonary blood flow was not affected by PBG. ANOVA indicated anatomic structure as the major determinant of pulmonary blood flow.

Does autonomic blockade reveal a potent contribution of nitric oxide to locomotion-induced vasodilation?

We sought to test the role of nitric oxide (NO) in governing skeletal muscle (iliac) vascular conductance during treadmill locomotion in dogs (n = 6; 3.2 and 6.4 km/h at 0% grade, and 6.4 km/h at 10% grade). As seen previously, the increase in muscle vascular conductance accompanying treadmill locomotion was little influenced by NO synthase inhibition alone with N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv), but the absolute value of conductance achieved during locomotion was reduced. Such ambiguous results provide an unclear picture regarding the importance of NO during locomotion. However, muscle vasodilation is normally restrained by the sympathetic system during locomotion. Thus a significant contribution by NO to the increase in vascular conductance that accompanies locomotion could be masked by partial withdrawal of the competing influence of sympathetic vasoconstrictor nerve activity secondary to the rise in arterial pressure following systemic L-NAME administration. To test this possibility, we compared the rise in muscle vascular conductance before and after L-NAME treatment while ganglionic transmission was blocked by hexamethonium. Under these conditions, L-NAME significantly reduced both the rise in vascular conductance (by 32%, P < 0.001) and the absolute level of vascular conductance (by 30%, P < 0.001) achieved during locomotion with no effect on blood flow. Thus augmented NO production normally provides a significant drive to relax vascular smooth muscle in active skeletal muscle during locomotion. Potential deficits stemming from the absence of NO following L-NAME treatment are masked by less intense sympathetic restraint when autonomic function is intact.

Muscle chemoreflex-induced increases in right atrial pressure.

When oxygen delivery to active muscle is too low for the ongoing rate of metabolism, metabolites accumulate and stimulate sensory nerves within the muscle leading to sympathetic activation (muscle chemoreflex). To date, studies on this reflex have focused primarily on its ability to increase arterial pressure or on the activity of the nerves that mediate this response. Clearly, a rise in cardiac output (CO) constitutes an important adjustment, because it increases the total blood flow available to be distributed among organs competing for flow. However, increments in heart rate and contractility provide limited means of raising CO because of the inverse relationship that exists between CO and right atrial pressure (RAP) in the intact circulation. Our goal was to test whether muscle chemoreflex activation, achieved via graded reductions in hindlimb blood flow by partial vascular occlusion, elicits peripheral vascular adjustments that raise RAP. In four conscious dogs exercising on a treadmill at 3.2 km/h 0% grade, RAP was well maintained during reflex activation despite increases in CO and arterial pressure that are expected to reduce RAP. Thus peripheral vascular adjustments elicited by the reflex successfully defend RAP in a setting where it would otherwise fall. To isolate the effects of the reflex on RAP, CO was maintained constant by ventricular pacing in conjunction with beta1-adrenergic blockade with atenolol. When the reflex was activated by reducing hindlimb blood flow from 0.6 to 0.3 l/min, RAP rose from 5.1 +/- 0.8 to 7.4 +/- 0.4 mmHg (P < 0.05) despite continued large (40 mmHg) increases in arterial pressure. During heavier exercise (6.4 km/h 10% grade) in five dogs with normal ventricular function, the reflex raised RAP from 5.7 +/- 0.9 to 6.6 +/- 0.8 mmHg (P < 0.05) despite increases in CO and arterial pressure. We conclude that the muscle chemoreflex is capable of eliciting substantial increases in RAP.

Flow-generating capability of the isolated skeletal muscle pump.

We sought to test directly whether the mechanical forces produced during rhythmic muscle contraction and relaxation act on the muscle vasculature in a manner sufficient to initiate and sustain blood flow. To accomplish this goal, we evaluated the mechanical performance of the isolated skeletal muscle pump. The hindlimb skeletal muscle pump was isolated by reversibly connecting the inferior vena cava and terminal aorta with extracorporeal tubing in 15- to 20-kg anesthetized pigs (n = 5). During electrically evoked contractions (1/s), hindlimb muscles were made to perfuse themselves by diverting the venous blood propelled out of the muscles into the shunt tubing, which had been prefilled with fresh arterial blood. This caused arterial blood to be pushed into the distal aorta and then through the muscles (shunt open, proximal aorta and vena cava clamped). In essence, the muscles perfused themselves for brief periods by driving blood around a "short-circuit" that isolates muscle from the remainder of the circulation, analogous to isolated heart-lung preparations. Because the large, short shunt offers a negligible resistance to flow, the arterial-venous pressure difference across the limbs was continuously zero, and thus the energy to drive flow through muscle could come only from the muscle pump. The increase in blood flow during normal heart-perfused contractions (with only the shunt tubing clamped) was compared with shunt-perfused contractions in which the large veins were preloaded with extra blood volume. Muscle blood flow increased by 87 +/- 11 and 110 +/- 21 (SE) ml/min in the first few seconds after the onset of shunt-perfused and heart-perfused contractions, respectively (P > 0.4). We conclude that the mechanical forces produced by muscle contraction and relaxation act on the muscle vasculature in a manner sufficient to generate a significant flow of blood.

Vascular endothelial growth factor/vascular permeability factor produces nitric oxide-dependent hypotension. Evidence for a maintenance role in quiescent adult endothelium.

In vitro studies suggest that vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) may stimulate release of nitric oxide (NO) from endothelial cells. To investigate the hemodynamic consequences of recombinant VEGF/VPF administered in vivo, recombinant human VEGF/VPF was administered as a bolus dose of 500 micrograms to anesthetized (n = 6) or conscious (n = 5) New Zealand White rabbits, as well as anesthetized rabbits with diet-induced hypercholesterolemia (HC; n = 7). Anesthetized Yorkshire farm pigs (no specific dietary pretreatment) were studied before and after receiving 500 micrograms intravenous (IV; n = 5) or intracoronary (IC; n = 5) VEGF/VPF. In anesthetized, normal rabbits, mean arterial pressure (MAP) fell by 20.5 +/- 1.4% (P < .05 versus baseline) within 3 minutes after IV VEGF/VPF. Pretreatment with N omega-nitro-L-arginine caused a significant inhibition of VEGF/VPF-induced hypotension. In conscious, normal rabbits, VEGF/VPF produced a consistent though lesser reduction in MAP. The fall in MAP induced by VEGF/VPF in anesthetized, HC rabbits (21.5 +/- 2.5% from baseline) was no different from that observed in normal anesthetized rabbits. In pigs, both IV and IC administration of VEGF/VPF produced a prompt reduction in MAP. Heart rate increased, while cardiac output, stroke volume, left atrial pressure, and total peripheral resistance all declined to a similar, statistically significant degree in both IV and IC groups. Epicardial echocardiography disclosed neither global nor segmental wall motion abnormalities in response to VEGF/VPF. We conclude that (1) VEGF/VPF-stimulated release of NO, previously suggested in vitro, occurs in vivo; (2) this finding suggests that functional VEGF/VPF receptors are present on quiescent adult endothelium, consistent with a maintenance function for VEGF/VPF, which may include regulation of NO; and (3) the preserved response of HC rabbits suggests that endothelial cell receptors for VEGF/VPF are spared in the setting of hypercholesterolemia.

Latency of muscle chemoreflex to vascular occlusion of active muscle during dynamic exercise.

When oxygen delivery to active muscle is too low for the ongoing rate of metabolism, metabolites accumulate and activate a muscle chemoreflex that raises arterial pressure. During static muscular contractions, the latency of the onset of increments in sympathetic activity attributed to the muscle chemoreflex is long (1-2 min). This long latency might be caused by slow accumulation of metabolites attributable to low rates of metabolism. Because shortening contractions at a given force per unit time have a much higher energy cost than do static contractions, the muscle chemoreflex should have a much shorter latency during dynamic exercise than during static contractions, and the latency should shorten further with rising exercise intensity. To test these ideas, the latency to the onset of the rise in arterial pressure induced by the muscle chemoreflex following vascular occlusion of active muscle was measured in four dogs exercising on a treadmill. During steady-state exercise of mild to moderate intensity, pressor responses to muscle ischemia were elicited by rapid, complete occlusion of the terminal aorta; this procedure mimics the blockage of muscle blood flow that occurs normally during static contractions. There was a statistically significant effect of exercise intensity on latency (P < 0.001). The latency was 23.5 +/- 4.5, 16.4 +/- 5.6, and 10.1 +/- 2.3 s (means +/- SE) at 3.2 km/h 0% grade, 6.5 km/h 0% grade, and 6.5 km/h 10% grade, respectively. Also, the rate of rise of arterial pressure during chemoreflex activation increased progressively with rising exercise intensity from 0.8 +/- 0.2 mmHg/s during exercise at 3.2 km/h 0% grade to 2.0 +/- 0.5 mmHg/s during exercise at 6.5 km/h 10% grade. Thus the latency of the muscle chemoreflex in response to vascular occlusion during mild dynamic exercise is shorter than has been reported during static contractions of moderate intensity.

Capacitive function of the heart: influence of acute changes in heart volume on mean right atrial pressure.

Net transfer of blood volume into or out of the cardiac chambers should have the same effect on central venous pressure as does transfer of an equal volume of blood to or from peripheral organs (e.g., spleen, or liver). We studied five pentobarbital sodium-anesthetized open-chest pigs (20-23 kg) to determine whether a reduction in the time-averaged volume of blood contained in the heart, induced by rapid atrial pacing, can raise right atrial pressure. A central premise of our study is that the mean value of right atrial pressure is acutely governed by the volume of blood that distends the central veins, and that atrial contractions primarily determine how atrial pressure varies about its mean value. To prevent changes in cardiac output from altering central blood volume and pressure, cardiac output during rapid pacing (2.36 +/- 0.18 l/min) was made to equal the resting output (2.35 +/- 0.16 l/min). This was achieved by selecting a rate of pacing at which the tendency for more frequent cardiac contractions to raise cardiac output was counterbalanced by the decrease in stroke volume induced by rapid pacing. Autonomic reflex mechanisms were attenuated by pharmacological blockade. Mean arterial pressure was minimally affected in the transition from a normal sinus rhythm (89 +/- 6 beats/min) to rapid atrial pacing (165 +/- 7 beats/min) in four pigs. Mean right atrial pressure rose abruptly from 2.8 +/- 0.5 mmHg during normal sinus rhythm to 3.5 +/- 0.5 mmHg (P = 0.015) at the onset of rapid pacing in these four pigs, presumably owing to decreased cardiac blood volume and a reciprocal expansion of central venous volume. In the fifth pig, a reduction in cardiac output induced by tachycardia led to a larger rise in mean right atrial pressure than did a reduction in cardiac output induced by bradycardia, presumably because tachycardia reduces cardiac blood volume whereas bradycardia raises cardiac volume. We conclude that the heart may play an important role in maintaining or raising its own filling pressure when heart rate rises.

VEGF improves myocardial blood flow but produces EDRF-mediated hypotension in porcine hearts.

Several recent studies have demonstrated the potential for improving myocardial perfusion by the continuous administration of angiogenic growth factors. Studies in our laboratory have shown that a single intraarterial or intravenous bolus of the endothelial cell specific mitogen vascular endothelial growth factor (VEGF) can significantly improve perfusion in a rabbit ischemic limb model. To test the efficacy of this therapeutic approach in chronic myocardial ischemia, 18 Yorkshire pigs underwent a left thoracotomy followed by placement of an ameroid constrictor around the proximal circumflex coronary artery. Gradual occlusion of the artery (26 +/- 4 days) was accompanied by identifiable hypokinesis of the posterolateral wall of the left ventricle (2D echo). Thirty days postoperatively, rhVEGF(165) (2 mg; n = 8) or saline (n = 10) was administered directly into the left coronary ostium. Postadenosine myocardial perfusion studies using colored microspheres 30 days later demonstrated superior blood flow in the ischemic zone of the VEGF-treated hearts (ischemic/normal ratio 1.09 vs 0.97, P < 0.05) compared with those receiving saline injection. Four of eight VEGF-treated animals succumbed, however, to severe hypotension following VEGF administration. Therefore 500 micrograms of VEGF were administered intracoronary to five normal pigs. A significant drop in mean arterial pressure (-44.4 +/- 3.2%, P < 0.05 vs baseline) and peripheral resistance (-13.2 +/- 4.5%, P < 0.05 vs baseline) was accompanied by increased heart rate. IV administration of N(omega)-nitro-L-arginine (L-NNA), an EDRF inhibitor, restored blood pressure to baseline. We conclude that a single intracoronary bolus of VEGF is capable of significantly augmenting flow to collateral-dependent ischemic myocardium. The associated hypotension appears to be EDRF-mediated. Further studies are needed to define the best dose and route of administration of VEGF for the treatment of coronary insufficiency.

Is the muscle metaboreflex important in control of blood flow to ischemic active skeletal muscle in dogs?

Ischemia of active skeletal muscle induces a reflex increase in sympathetic activity, heart rate, cardiac output, and arterial pressure, termed the muscle metaboreflex. Whether this pressor response contributes importantly in the regulation of blood flow to the ischemic active skeletal muscle is not well understood. If the pressor response is achieved without substantial vasoconstriction in the ischemic muscle, this increase in arterial pressure would act to improve muscle blood flow. Dogs performed treadmill exercise at mild (3.2 km/h, 0% grade) and moderate (6.4 km/h, 10% grade) workloads. During each workload, resistance to blood flow in the hindlimbs (Rh) was increased via graded partial inflation of a vascular occluder implanted on the terminal aorta. The closed-loop gain of the muscle metaboreflex (Gcl) was calculated, based on the steady-state changes in terminal aortic blood flow (TAQ). If no pressor response occurred, then TAQ should decrease in proportion to the increase in total Rh (the sum of resistance due to partial vascular occlusion and hindlimb vascular resistance); i.e., no reflex restoration of hindlimb blood flow would occur. However, with a reflex increase in systemic arterial pressure, TAQ could rise above the level predicted on the basis of the increase in Rh. We observed that with the initial increase in Rh during mild exercise, Gcl was not significantly different from zero (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of cardiac output distribution on cardiac filling pressure during rest and dynamic exercise in dogs.

The distribution of cardiac output (CO) between compliant and noncompliant organs is an important determinant of the slope of the relationship predicted between CO and right atrial pressure (RAP). However, curves relating CO to RAP at rest are shifted rightward (higher CO) and upward (higher RAP) by exercise with no change in slope, despite a large rise in the fraction of CO directed to noncompliant muscle vasculature, which is predicted to decrease the slope. We sought to test whether reductions in CO imposed during rest and exercise are accompanied by changes in its distribution that would favor constant slopes. Six dogs had atrioventricular block produced surgically and had blood flow transducers implanted on the ascending aorta and the terminal aorta. Total muscle blood flow (MBF) was estimated from terminal aortic flow by assuming that all of the increase in CO in mild dynamic exercise is directed to muscle. CO was reduced by lowering ventricular pacing rate at rest and during graded treadmill exercise (2 and 4 miles/h at 0% grade). Exercise increased the fraction of CO directed to muscle (MBF/CO) (P < 0.001). The effect of changes in CO on MBF/CO depended on exercise intensity (P < 0.01). At rest, MBF/CO fell from 0.53 to 0.45 when CO was reduced; this is expected to reduce the slope of the measured relationship between CO and RAP. During exercise at 2 miles/h, MBF/CO changed little when CO was reduced.(ABSTRACT TRUNCATED AT 250 WORDS)

Is rapid rise in vascular conductance at onset of dynamic exercise due to muscle pump?

We tested the hypothesis that rapid increases in muscle blood flow and vascular conductance (C) at onset of dynamic exercise are caused by the muscle pump. We measured arterial (AP) and central venous pressure (CVP) in nine awake dogs, eight with atrioventricular block, pacemakers, and ascending aortic flow probes for control of cardiac output (CO) (2 also had terminal aortic flow probes). One dog had only an iliac artery probe. At exercise onset (0 and 10% grade, 4 mph) C and CVP rose to early plateaus, and AP reached a nadir, all in 2-5 s. At 20% grade and 4 mph, C increased continuously after its initial sudden rise. Timing and magnitude of initial change in conductance (delta C) were independent of CO, AP, work rate (change in grade at constant speed), or autonomic function (blocked by hexamethonium). Speed of initial delta C and its independence from work rate and blood flow ruled out metabolic vasodilation as its cause; insensitivity to AP and autonomic blockade ruled out myogenic relaxation and sympathetic vasodilation as causes of sudden delta C. Sensitivity to contraction frequency (not work per se) implicates the muscle pump. When reflexes were blocked, a large secondary rise in C, presumably caused by metabolic vasodilation, began after 10 s of mild exercise. When reflexes were intact in mild exercise, C was lowered below its initial plateau by sympathetic vasoconstriction, which partially raised AP from its nadir toward its preexercise level. Our conclusion is that dynamic exercise has a large rapid effect on C that is not explained by known neural, metabolic, myogenic, or hydrostatic influences.(ABSTRACT TRUNCATED AT 250 WORDS)

Dependence of cardiac filling pressure on cardiac output during rest and dynamic exercise in dogs.

At rest, central venous pressure (CVP) falls when cardiac output (CO) rises. This can be attributed to flow-dependent redistribution of blood volume from central to peripheral blood vessels. In contrast, CVP rises during dynamic exercise despite a rise in CO. Therefore peripheral circulatory changes during exercise must counteract the factors that lower CVP when CO rises during rest. Our objectives were to determine the importance of blood flow, the muscle pump, and reflexes on changes in ventricular filling pressure during dynamic exercise. In seven dogs with a surgically produced atrioventricular (AV) block, normal relationships between CO and CVP were established by AV-linked pacing (normal heart rates) during rest and exercise. Cardiac output was altered during rest and treadmill exercise (4 miles/h at 0, 10, or 20% grade) by changing ventricular pacing rate to establish curves relating delta CVP to delta CO. These curves were displaced rightward (higher CO) and upward (higher CVP) by exercise because of the muscle pump. Changing CO by pacing during rest and exercise revealed a constant slope for delta CVP/delta CO of -2.7 mmHg.l-1.min-1. Blockade of reflex vasoconstriction and venoconstriction with hexamethonium at rest and during mild exercise (to isolate effects of the muscle pump) did not alter these slopes or the displacement of the curves by exercise, although CVP was 4.3 mmHg lower at a given CO after blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Basal metabolism adds a significant offset to unloaded myocardial oxygen consumption per minute.

Myocardial oxygen consumption (MVO2) includes components for 1) mechanical energy generation, 2) activation, and 3) basal metabolism. Whereas the first two components are expected to increase in proportion with heart rate, a significant basal level of metabolism would consume oxygen even if the heart rate were zero. Contrary to this expectation, however, a previous study reported that, during unloaded beats, MVO2 per beat (which includes basal metabolism) was independent of heart rate. Accordingly, unloaded MVO2 per minute would extrapolate to zero at zero heart rate; this result is unexpected considering basal metabolism. To resolve this inconsistency, we varied heart rate over a wide range after inducing atrioventricular block in eight isolated cross-circulated canine hearts that contracted isovolumically. We examined whether a term representing rate-independent basal metabolism was needed to describe MVO2 per minute. Mechanical energy generated by the left ventricle was evaluated from the pressure-volume area, which was altered by changing isovolumic ventricular volume over at least five levels at each heart rate. Contractility, evaluated by the slope of the end-systolic pressure-volume relation, did not vary significantly with heart rate in this study. In contrast to the previous report, unloaded MVO2 per beat (i.e., MVO2 extrapolated to a pressure-volume area of zero) was not constant but fell monotonically with increases in heart rate in every heart. We considered that this trend was caused by a significant rate-independent basal level of MVO2 per minute. Multiple linear regression analysis confirmed that this rate-independent basal term differed significantly from zero in seven of the eight hearts studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Baroreflex attenuates pressor response to graded muscle ischemia in exercising dogs.

Graded reductions in hindlimb perfusion in dogs exercising at 2 miles/h (0% grade) elicited reflex pressor responses by what is referred to as the "muscle chemoreflex." To determine the extent to which arterial baroreceptor reflexes oppose the muscle chemoreflex, we elicited pressor responses to muscle ischemia before and after chronic surgical denervation of the arterial baroreceptors. The muscle chemoreflex showed a threshold beyond which systemic pressure rose approximately 3 mmHg for each 1-mmHg decrease in hindlimb perfusion pressure when the arterial baroreceptors were intact. Arterial baroreceptor denervation approximately doubled the pressor responses, i.e., systemic pressure rose by approximately 6 mmHg for each 1-mmHg fall in hindlimb perfusion pressure, without alteration in threshold. We conclude that during mild dynamic exercise, the arterial baroreflexes oppose the pressor response to graded reductions in hindlimb perfusion, reducing it by approximately 50%. When unopposed by the arterial baroreflexes the muscle chemoreflex exhibits a gain (ratio of change in systemic pressure to change in hindlimb perfusion pressure) of approximately -6; thus this reflex can correct by 85% the decrease in muscle perfusion pressure caused by partial vascular occlusion.