Spontaneous baroreflex control of cardiac output during dynamic exercise, muscle metaboreflex activation, and heart failure

We have previously shown that spontaneous baroreflex-induced changes in heart rate (HR) do not always translate into changes in cardiac output (CO) at rest. We have also shown that heart failure (HF) decreases this linkage between changes in HR and CO. Whether dynamic exercise and muscle metaboreflex activation (via imposed reductions in hindlimb blood flow) further alter this translation in normal and HF conditions is unknown. We examined these questions using conscious, chronically instrumented dogs before and after pacing-induced HF during mild and moderate dynamic exercise with and without muscle metaboreflex activation. We measured left ventricular systolic pressure (LVSP), CO, and HR and analyzed the spontaneous HR-LVSP and CO-LVSP relationships. In normal animals, mild exercise significantly decreased HR-LVSP (-3.08 +/- 0.5 vs. -5.14 +/- 0.6 beats.min(-1).mmHg(-1); P < 0.05) and CO-LVSP (-134.74 +/- 24.5 vs. -208.6 +/- 22.2 ml.min(-1).mmHg(-1); P < 0.05). Moderate exercise further decreased both and, in addition, significantly reduced HR-CO translation (25.9 +/- 2.8% vs. 52.3 +/- 4.2%; P < 0.05). Muscle metaboreflex activation at both workloads decreased HR-LVSP, whereas it had no significant effect on CO-LVSP and the HR-CO translation. HF significantly decreased HR-LVSP, CO-LVSP, and the HR-CO translation in all situations. We conclude that spontaneous baroreflex HR responses do not always cause changes in CO during exercise. Moreover, muscle metaboreflex activation during mild and moderate dynamic exercise reduces this coupling. In addition, in HF the HR-CO translation also significantly decreases during both workloads and decreases even further with muscle metaboreflex activation.     

Muscle metaboreflex attenuates spontaneous heart rate baroreflex sensitivity during dynamic exercise

Hypoperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex. Dynamic exercise attenuates spontaneous baroreflex sensitivity (SBRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure (BP). Our objective was to determine whether muscle metaboreflex activation (MRA) further diminishes SBRS. Conscious dogs were chronically instrumented for measurement of HR, cardiac output, mean arterial pressure, and left ventricular systolic pressure (LVSP) at rest and during mild (3.2 km/h) or moderate (6.4 km/h at 10% grade) dynamic exercise before and after MRA (via partial reduction of hindlimb blood flow). SBRS was evaluated as the slopes of the linear relations (LRs) between HR and LVSP during spontaneous sequences of at least three consecutive beats when HR changed inversely vs. pressure (expressed as beats x min(-1) x mmHg(-1)). During mild exercise, these LRs shifted upward, with a significant decrease in SBRS (-3.0 +/- 0.4 vs. -5.2 +/- 0.4, P<0.05 vs. rest). MRA shifted LRs upward and rightward and decreased SBRS (-2.1 +/- 0.1, P<0.05 vs. mild exercise). Moderate exercise shifted LRs upward and rightward and significantly decreased SBRS (-1.2 +/- 0.1, P<0.05 vs. rest). MRA elicited further upward and rightward shifts of the LRs and reductions in SBRS (-0.9 +/- 0.1, P<0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher BP and HR as exercise intensity increases. In addition, increases in exercise intensity, as well as MRA, attenuate SBRS.     

Attenuated arterial baroreflex buffering of muscle metaboreflex in heart failure

Previous studies have shown that heart failure (HF) or sinoaortic denervation (SAD) alters the strength and mechanisms of the muscle metaboreflex during dynamic exercise. However, it is still unknown to what extent SAD may modify the muscle metaboreflex in HF. Therefore, we quantified the contribution of cardiac output (CO) and peripheral vasoconstriction to metaboreflex-mediated increases in mean arterial blood pressure (MAP) in conscious, chronically instrumented dogs before and after induction of HF in both barointact and SAD conditions during mild and moderate exercise. The muscle metaboreflex was activated via partial reductions in hindlimb blood flow. After SAD, the metaboreflex pressor responses were significantly higher with respect to the barointact condition despite lower CO responses. The pressor response was significantly lower in HF after SAD but still higher than that of HF in the barointact condition. During control experiments in the barointact condition, total vascular conductance summed from all beds except the hindlimbs did not change with muscle metaboreflex activation, whereas in the SAD condition both before and after induction of HF significant vasoconstriction occurred. We conclude that SAD substantially increased the contribution of peripheral vasoconstriction to metaboreflex-induced increases in MAP, whereas in HF SAD did not markedly alter the patterns of the reflex responses, likely reflecting that in HF the ability of the arterial baroreflex to buffer metaboreflex responses is impaired.     

Cardiovascular responses to exercise and muscle metaboreflex activation during the recovery from pacing-induced heart failure.

Rapid recovery of resting hemodynamics from tachycardia- or arrhythmia-induced heart failure (HF) has been demonstrated in both humans and animals. However, little is known about cardiovascular responses to exercise in animals or about reflex control of the cardiovascular system during exercise while recovering from HF. Inasmuch as the reduced cardiac output (CO) during exercise in HF has been shown to lead to underperfusion of active skeletal muscle and tonic activation of the muscle metaboreflex, an improved CO during exercise in subjects recovering from HF may lead to higher skeletal muscle blood flows and to relief of this metabolic stimulus. We investigated cardiovascular responses to graded treadmill exercise and metaboreflex activation [evoked by imposed graded reductions in hindlimb blood flow (HLBF) during mild and moderate exercise] in chronically instrumented dogs during control, mild to moderate HF (induced by rapid ventricular pacing), and recovery from HF. Most hemodynamic responses to graded exercise returned to control within 24 h of disconnecting the pacemaker. After 2 wk of recovery, CO and HLBF at each workload were significantly higher than control. In addition, whereas the increase in CO that normally occurs with metaboreflex activation was markedly attenuated in HF, it completely returned in the recovery experiments. We conclude that cardiovascular responses to graded exercise during the recovery from pacing-induced HF return rapidly to near or above control and that the increased CO and HLBF in recovery likely relieved the metabolic stimulus and tonic metaboreflex activation that may have occurred during moderate exercise in HF.     

Arterial baroreflex alters strength and mechanisms of muscle metaboreflex during dynamic exercise

Previous studies showed that the arterial baroreflex opposes the pressor response mediated by muscle metaboreflex activation during mild dynamic exercise. However, no studies have investigated the mechanisms contributing to metaboreflex-mediated pressor responses during dynamic exercise after arterial baroreceptor denervation. Therefore, we investigated the contribution of cardiac output (CO) and peripheral vasoconstriction in mediating the pressor response to graded reductions in hindlimb perfusion in conscious, chronically instrumented dogs before and after sinoaortic denervation (SAD) during mild and moderate exercise. In control experiments, the metaboreflex pressor responses were mediated via increases in CO. After SAD, the metaboreflex pressor responses were significantly greater and significantly smaller increases in CO occurred. During control experiments, nonischemic vascular conductance (NIVC) did not change with muscle metaboreflex activation, whereas after SAD NIVC significantly decreased with metaboreflex activation; thus SAD shifted the mechanisms of the muscle metaboreflex from mainly increases in CO to combined cardiac and peripheral vasoconstrictor responses. We conclude that the major mechanism by which the arterial baroreflex buffers the muscle metaboreflex is inhibition of metaboreflex-mediated peripheral vasoconstriction.     

Modulation of spontaneous baroreflex control of heart rate and indexes of vagal tone by passive calf muscle stretch during graded metaboreflex activation in humans.

We examined whether spontaneous baroreflex modulation of heart rate and other indexes of cardiac vagal tone could be altered by passive stretch of the human calf muscle during graded concurrent activation of the muscle metaboreflex. Ten healthy subjects performed four trials: a control trial, resting for 1.5 min (0% trial); or 1.5 min of one-legged isometric plantar flexor exercise at 30, 50, and 70% maximal voluntary contraction. The incremental increases in blood pressure (BP) caused were then partially sustained by subsequent local circulatory occlusion (CO). After 3.5 min of CO alone, sustained calf stretch and CO were applied for 3 min. Spontaneous baroreflex sensitivity (SBRS) was progressively decreased with increasing exercise intensity (P < 0.05). During CO, stretch decreased SBRS and increased BP similarly in all trials (P < 0.05). Within 15 s of stretch onset, heart rate (HR) increased by 6 +/- 1, 6 +/- 1, 8 +/- 1, and 6 +/- 2 beats/min in the 0, 30, 50, and 70% trials, respectively (P < 0.05), and root mean square of successive differences was decreased from CO-alone levels (P < 0.05). During the second and third minutes of stretch, HR fell back but remained significantly above CO levels, and common coefficient of variance of R-R interval decreased progressively with increasing prior exercise intensity (P < 0.05; 70% trial). This suggests that passive stretch of the human calf muscles decreases cardiac vagal outflow irrespective of the levels of BP increase caused by muscle metaboreflex activation and implies that central modulation of baroreceptor input, mediated by the actions of stretch-activated mechanoreceptive muscle afferent fibers, continues.     

Heart failure attenuates muscle metaboreflex control of ventricular contractility during dynamic exercise

Underperfusion of active skeletal muscle elicits a reflex pressor response termed the muscle metaboreflex (MMR). In normal dogs during mild exercise, MMR activation causes large increases in cardiac output (CO) and mean arterial pressure (MAP); however, in heart failure (HF) although MAP increases, the rise in CO is virtually abolished, which may be due to an impaired ability to increase left ventricular contractility (LVC). The objective of the present study was to determine whether the increases in LVC seen with MMR activation during dynamic exercise in normal animals are abolished in HF. Conscious dogs were chronically instrumented to measure CO, MAP, and left ventricular (LV) pressure and volume. LVC was calculated from pressure-volume loop analysis [LV maximal elastance (E(max)) and preload-recruitable stroke work (PRSW)] at rest and during mild and moderate exercise under free-flow conditions and with MMR activation (via partial occlusion of hindlimb blood flow) before and after rapid ventricular pacing-induced HF. In control experiments, MMR activation at both workloads [mild exercise (3.2 km/h) and moderate exercise (6.4 km/h at 10% grade)] significantly increased CO, E(max), and PRSW. In contrast, after HF was induced, CO, E(max), and PRSW were significantly lower at rest. Although CO increased significantly from rest to exercise, E(max) and PRSW did not change. In addition, MMR activation caused no significant change in CO, E(max), or PRSW at either workload. We conclude that MMR causes large increases in LVC in normal animals but that this ability is abolished in HF.     

Spontaneous baroreflex control of heart rate versus cardiac output: altered coupling in heart failure

Dynamic cardiac baroreflex responses are frequently investigated by analyzing the spontaneous reciprocal changes in arterial pressure and heart rate (HR). However, whether the spontaneous baroreflex-induced changes in HR translate into changes in cardiac output (CO) is unknown. In addition, this linkage between changes in HR and changes in CO may be different in subjects with heart failure (HF). We examined these questions using conscious dogs before and after pacing-induced HF. Spontaneous baroreflex sensitivity in the control of HR and CO was evaluated as the slopes of the linear relationships between HR or CO and left ventricular systolic pressure (LVSP) during spontaneous sequences of greater or equal to three consecutive beats when HR or CO changed inversely versus pressure. Furthermore, the translation of baroreflex HR responses into CO responses (HR-CO translation) was examined by computing the overlap between HR and CO sequences. In normal resting conditions, 44.0 +/- 4.4% of HR sequences overlapped with CO sequences, suggesting that only around half of the baroreflex HR responses cause CO responses. In HF, HR-LVSP, CO-LVSP, and the HR-CO translation significantly decreased compared with the normal condition (-2.29 +/- 0.5 vs. -5.78 +/- 0.7 beats.min(-1).mmHg(-1); -70.95 +/- 11.8 vs. -229.89 +/- 29.6 ml.min(-1).mmHg(-1); and 19.66 +/- 4.9 vs. 44.0 +/- 4.4%, respectively). We conclude that spontaneous baroreflex HR responses do not always cause changes in CO. In addition, HF significantly decreases HR-LVSP, CO-LVSP, and HR-CO translation.     

Impaired central hemodynamic response and exaggerated vasoconstriction during muscle metaboreflex activation in heart failure patients

The muscle metaboreflex is enhanced in chronic heart failure (CHF) patients, and this fact has been associated with the early fatigue shown by these patients in response to exercise. In animal studies of CHF, it was found that the limited capacity to enhance ventricular performance is responsible for a functional shift from a cardiac output to a systemic vascular resistance (SVR) increase in the mechanism by which the cardiovascular system raises blood pressure in response to the metaboreflex. However, the existence of this functional shift is still unknown in humans. The present study was undertaken to test the hypothesis that a similar hemodynamic response was also present in humans with CHF. The hemodynamic response to metaboreflex activation obtained through postexercise ischemia was assessed in nine patients with CHF and nine healthy controls (CTL) by means of impedance cardiography. The main results were that 1) the blood pressure rise due to the metaboreflex was similar in the two groups; 2) the CTL group achieved the blood pressure response via cardiac output increase, and the CHF group, via SVR increase; and 3) stroke volume was enhanced in the CTL group and decreased in the CHF group. This study demonstrates that in CHF patients, metaboreflex recruitment causes a functional shift from flow increase to peripheral vasoconstriction in the mechanism through which blood pressure is increased. The incapacity to enhance cardiac performance and stroke volume is probably the primary cause of this cardiovascular alteration.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.     

Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 +/- 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to -80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 +/- 3 mmHg) and was further augmented during PEI-H (+26 +/- 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (-0.51 +/- 0.09, -0.48 +/- 0.13, and -0.49 +/- 0.12 beats.min(-1).mmHg(-1) for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H (P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.     

Interaction between muscle metaboreflex and mechanoreflex modulation of arterial baroreflex sensitivity in exercise.

The effect of external calf compression on baroreflex sensitivity (BRS) during electrically evoked plantar flexion and postexercise circulatory occlusion (PECO) was studied. Subjects took part in two experimental trials: control and compression. In both trials, electrically evoked isometric plantarflexion (Stim) was performed at 30% maximum voluntary contraction force for 2 min. During compression, a cuff (inflated to 250 mmHg) was applied to the active calf during exercise and PECO. Sequence analysis carried out on the systolic blood pressure responses, and R-wave-R-wave intervals revealed a rightward shift of the regression line along the pressure axis during Stim in both trials. In the control experiment, BRS was significantly (P < 0.01) increased from 10.37 +/- 1.87 ms/mmHg during Stim to 12.79 +/- 1.62 ms/mmHg during PECO. With external compression, BRS was unaltered between Stim (10.84 +/- 1.86 ms/mmHg) and PECO (11.40 +/- 1.54 ms/mmHg). Because the metabolic conditions were the same in both experiments, the results may best be explained by reactivation of muscle mechanoreceptor activity by external compression during PECO.     

Altered muscle metaboreflex control of coronary blood flow and ventricular function in heart failure

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF), coronary vascular conductance (CVC), and regional left ventricular performance in conscious, chronically instrumented dogs during treadmill exercise before and after the induction of heart failure (HF). In control experiments, muscle metaboreflex activation during mild exercise elicited significant reflex increases in mean arterial pressure, heart rate, and cardiac output. CBF increased significantly, whereas no significant change in CVC occurred. There was no significant change in the minimal rate of myocardial shortening (-dl/dt(min)) with muscle metaboreflex activation during mild exercise (15.5 +/- 1.3 to 16.8 +/- 2.4 mm/s, P > 0.05); however, the maximal rate of myocardial relaxation (+dl/dt(max)) increased (from 26.3 +/- 4.0 to 33.7 +/- 5.7 mm/s, P < 0.05). Similar hemodynamic responses were observed with metaboreflex activation during moderate exercise, except there were significant changes in both -dl/dt(min) and dl/dt(max). In contrast, during mild exercise with metaboreflex activation during HF, no significant increase in cardiac output occurred, despite a significant increase in heart rate, inasmuch as a significant decrease in stroke volume occurred as well. The increases in mean arterial pressure and CBF were attenuated, and a significant reduction in CVC was observed (0.74 +/- 0.14 vs. 0.62 +/- 0.12 ml x min(-1) x mmHg(-1); P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either -dl/dt(min) or +dl/dt(max) during mild exercise in HF. We conclude that during HF the elevated muscle metaboreflex-induced increases in sympathetic tone to the heart functionally vasoconstrict the coronary vasculature, which may limit increases in myocardial performance.     

Modulation of arterial baroreflex control of muscle sympathetic nerve activity by muscle metaboreflex in humans

We aimed to investigate the interaction [with respect to the regulation of muscle sympathetic nerve activity (MSNA) and blood pressure] between the arterial baroreflex and muscle metaboreflex in humans. In 10 healthy subjects who performed a 1-min sustained handgrip exercise at 50% maximal voluntary contraction followed by forearm occlusion, arterial baroreflex control of MSNA (burst incidence and strength and total activity) was evaluated by analyzing the relationship between beat-by-beat spontaneous variations in diastolic arterial blood pressure (DAP) and MSNA both during supine rest (control) and during postexercise muscle ischemia (PEMI). During PEMI (vs. control), 1) the linear relationship between burst incidence and DAP was shifted rightward with no alteration in sensitivity, 2) the linear relationship between burst strength and DAP was shifted rightward and upward with no change in sensitivity, and 3) the linear relationship between total activity and DAP was shifted to a higher blood pressure and its sensitivity was increased. The modification of the control of total activity that occurs in PEMI could be a consequence of alterations in the baroreflex control of both MSNA burst incidence and burst strength. These results suggest that the arterial baroreflex and muscle metaboreflex interact to control both the occurrence and strength of MSNA bursts.     

Chemoreflex and metaboreflex control during static hypoxic exercise

To investigate the effects of muscle metaboreceptor activation during hypoxic static exercise, we recorded muscle sympathetic nerve activity (MSNA), heart rate, blood pressure, ventilation, and blood lactate in 13 healthy subjects (22 +/- 2 yr) during 3 min of three randomized interventions: isocapnic hypoxia (10% O(2)) (chemoreflex activation), isometric handgrip exercise in normoxia (metaboreflex activation), and isometric handgrip exercise during isocapnic hypoxia (concomitant metaboreflex and chemoreflex activation). Each intervention was followed by a forearm circulatory arrest to allow persistent metaboreflex activation in the absence of exercise and chemoreflex activation. Handgrip increased blood pressure, MSNA, heart rate, ventilation, and lactate (all P < 0.001). Hypoxia without handgrip increased MSNA, heart rate, and ventilation (all P < 0.001), but it did not change blood pressure and lactate. Handgrip enhanced blood pressure, heart rate, MSNA, and ventilation responses to hypoxia (all P < 0.05). During circulatory arrest after handgrip in hypoxia, heart rate returned promptly to baseline values, whereas ventilation decreased but remained elevated (P < 0.05). In contrast, MSNA, blood pressure, and lactate returned to baseline values during circulatory arrest after hypoxia without exercise but remained markedly increased after handgrip in hypoxia (P < 0.05). We conclude that metaboreceptors and chemoreceptors exert differential effects on the cardiorespiratory and sympathetic responses during exercise in hypoxia.     

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity

Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation on arterial baroreceptor sensitivity, determined as the alpha index between oscillations in systolic BP (SBP) generated by respiration and oscillations present in R-R intervals (RR) and in peripheral sympathetic nerve traffic [muscle sympathetic nerve activity (MSNA)]. Tidal volume increased from 478 +/- 24 to 1,499 +/- 84 ml and raised SBP from 118 +/- 2 to 125 +/- 3 mmHg, whereas RR decreased from 947 +/- 18 to 855 +/- 11 ms (all P < 0.0001); MSNA did not change. Hyperventilation reduced arterial baroreflex sensitivity to oscillations in SBP at both cardiac (from 13 +/- 1 to 9 +/- 1 ms/mmHg, P < 0.001) and MSNA levels (by -37 +/- 5%, P < 0.0001). Thus increased BP during hyperventilation does not elicit any reduction in either heart rate or MSNA. Baroreflex modulation of RR and MSNA in response to hyperventilation-induced BP oscillations is attenuated. Blunted baroreflex gain during hyperventilation may be a mechanism that facilitates simultaneous increases in BP, heart rate, and sympathetic activity during dynamic exercise and chemoreceptor activation.     

Muscle metaboreflex control of ventricular contractility during dynamic exercise

When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, afferent nerves within muscles are activated, which elicit reflex increases in heart rate (HR), cardiac output (CO), and arterial pressure (AP), termed the muscle metaboreflex (MMR). To what extent the increases in CO are the result of increased ventricular contractility is unclear. A widely accepted index of contractility is maximal left ventricular elastance (Emax), the slope of the end-systolic pressure-volume relationship, such as during rapidly imposed reductions in preload. The objective of the present study was to determine whether MMR activation elicits increases in Emax. Experiments were performed using conscious dogs chronically instrumented to measure left ventricular pressure and volume at rest and during mild or moderate treadmill exercise with and without partial hindlimb ischemia to elicit MMR responses. At both workloads, MMR activation significantly increased CO, HR, AP, and maximum rate of change of left ventricular pressure. During both mild and moderate exercise, MMR activation increased Emax to 159.6 +/- 8.83 and 155.8 +/- 6.32% of the exercise value under free-flow conditions, respectively. We conclude that the increase of ventricular elastance associated with MMR activation indicates that a substantial increase in ventricular contractility contributes to the rise in CO during dynamic exercise.