Severe exercise alters the strength and mechanisms of the muscle metaboreflex

2001 ◽  
Vol 280 (4) ◽  
pp. H1645-H1652 ◽  
Author(s):  
Robert A. Augustyniak ◽  
Heidi L. Collins ◽  
Eric J. Ansorge ◽  
Noreen F. Rossi ◽  
Donal S. O'Leary
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Treadmill Exercise ◽  
Pressor Response ◽  
Increase Blood Flow ◽  
Moderate Exercise ◽  
Muscle Metaboreflex ◽  
Severe Exercise

Previous studies have shown that in dogs performing mild to moderate treadmill exercise, partial graded reductions in hindlimb blood flow cause active skeletal muscle to become ischemic and metabolites to accumulate thus evoking the muscle metaboreflex. This leads to a substantial reflex increase in mean arterial pressure (MAP) mediated almost solely via a rise in cardiac output (CO). However, during severe exercise CO is likely near maximal and thus metaboreflex-mediated increases in MAP may be attenuated. We therefore evoked the metaboreflex via partial graded reductions in hindlimb blood flow in seven dogs during mild, moderate, and severe treadmill exercise. During mild and moderate exercise there was a large rise in CO (1.5 ± 0.2 and 2.2 ± 0.3 l/min, respectively), whereas during severe exercise no significant increase in CO occurred. The rise in CO caused a marked pressor response that was significantly attenuated during severe exercise (26.3 ± 7.0, 33.2 ± 5.6, and 12.2 ± 4.8 mmHg, respectively). We conclude that during severe exercise the metaboreflex pressor response mechanisms are altered such that the ability of this reflex to increase CO is abolished, and reduced pressor response occurs only via peripheral vasoconstriction. This shift in mechanisms likely limits the effectiveness of the metaboreflex to increase blood flow to ischemic active skeletal muscle. Furthermore, because the metaboreflex is a flow-raising reflex and not a pressure-raising reflex, it may be most appropriate to describe the metaboreflex magnitude based on its ability to evoke a rise in CO and not a rise in MAP.

Chronic Ablation of TRPV1 Sensitive Skeletal Muscle Afferents Attenuates the Muscle Metaboreflex

2021 ◽  
Author(s):  
Joseph Mannozzi ◽  
Mohamed-Hussein Al-Hassan ◽  
Beruk Lessanework ◽  
Alberto Alvarez ◽  
Danielle Senador ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Skeletal Muscle ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Intrathecal Administration ◽  
Exercise Intolerance ◽  
Stroke Work ◽  
Muscle Metaboreflex

Exercise intolerance is a hallmark symptom of cardiovascular disease and likely occurs via enhanced activation of muscle metaboreflex- induced vasoconstriction of the heart and active skeletal muscle which, thereby limits cardiac output and peripheral blood flow. Muscle metaboreflex vasoconstrictor responses occur via activation of metabolite-sensitive afferent fibers located in ischemic active skeletal muscle, some of which express Transient Receptor Potential Vanilloid 1 (TRPV1) cation channels. Local cardiac and intrathecal administration of an ultra-potent noncompetitive, dominant negative agonist resiniferatoxin (RTX) can ablate these TRPV1 sensitive afferents. This technique has been used to attenuate cardiac sympathetic afferents and nociceptive pain. We investigated whether intrathecal administration (L4-L6) of RTX (2 μg/kg) could chronically attenuate subsequent muscle metaboreflex responses elicited by reductions in hindlimb blood flow during mild exercise (3.2 km/h) in chronically instrumented conscious canines. RTX significantly attenuated metaboreflex induced increases in mean arterial pressure (27 ± 5.0 mmHg vs. 6 ± 8.2 mmHg), cardiac output (1.40 ± 0.2 L/min vs. 0.28 ± 0.1 L/min) and stroke work (2.27 ± 0.2 L*mmHg vs. 1.01 ± 0.2 L*mmHg). Effects were maintained until 78 ± 14 days post RTX at which point the efficacy of RTX injection was tested by intra-arterial administration of capsaicin (20 μg/kg). A significant reduction in the mean arterial pressure response (+45.7 ± 6.5 mmHg pre RTX vs +19.7 ± 3.1mmHg post RTX) was observed. We conclude that intrathecal administration of RTX can chronically attenuate the muscle metaboreflex and could potentially alleviate enhanced sympatho-activation observed in cardiovascular disease states.

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

2005 ◽  
Vol 288 (3) ◽  
pp. H1381-H1388 ◽  
Author(s):  
Eric J. Ansorge ◽  
Robert A. Augustyniak ◽  
Mariana L. Perinot ◽  
Robert L. Hammond ◽  
Jong-Kyung Kim ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Blood Flow ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Coronary Blood Flow ◽  
Moderate Exercise ◽  
Muscle Metaboreflex ◽  
Significant Change

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 (−d l/d tmin) 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 (+d l/d tmax) 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 −d l/d tmin and d l/d tmax. 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·min−1·mmHg−1; P < 0.05). Similar results were observed during moderate exercise in HF. Muscle metaboreflex activation did not elicit significant changes in either −d l/d tmin or +d l/d tmax 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.

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

1995 ◽  
Vol 268 (3) ◽  
pp. H980-H986 ◽  
Author(s):  
D. S. O'Leary ◽  
D. D. Sheriff
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Muscle Blood Flow ◽  
Vascular Occlusion ◽  
Systemic Arterial Pressure ◽  
Initial Increase ◽  
Aortic Blood Flow ◽  
Muscle Metaboreflex

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)

Muscle metaboreflex control of coronary blood flow

2002 ◽  
Vol 283 (2) ◽  
pp. H526-H532 ◽  
Author(s):  
Eric J. Ansorge ◽  
Sachin H. Shah ◽  
Robert A. Augustyniak ◽  
Noreen F. Rossi ◽  
Heidi L. Collins ◽  
...  
Keyword(s):  
Blood Flow ◽  
Coronary Blood Flow ◽  
Adrenergic Receptor ◽  
Sympathetic Nerve Activity ◽  
Treadmill Exercise ◽  
Cardiac Work ◽  
Nerve Activity ◽  
Muscle Metaboreflex ◽  
Severe Exercise ◽  
Chronically Instrumented Dogs

We investigated the effect of muscle metaboreflex activation on left circumflex coronary blood flow (CBF) and vascular conductance (CVC) in conscious, chronically instrumented dogs during treadmill exercise ranging from mild to severe workloads. Metaboreflex responses were also observed during mild exercise with constant heart rate (HR) of 225 beats/min and β1-adrenergic receptor blockade to attenuate the substantial reflex increases in cardiac work. The muscle metaboreflex was activated via graded partial occlusion of hindlimb blood flow. During mild exercise, with muscle metaboreflex activation, hindlimb ischemia elicited significant reflex increases in mean arterial pressure (MAP), HR, and cardiac output (CO) (+39.0 ± 5.2 mmHg, +29.9 ± 7.7 beats/min, and +2.0 ± 0.4 l/min, respectively; all changes, P < 0.05). CBF increased from 51.9 ± 4.3 to 88.5 ± 6.6 ml/min, ( P < 0.05), whereas no significant change in CVC occurred (0.56 ± 0.06 vs. 0.59 ± 0.05 ml · min−1 · mmHg−1; P > 0.05). Similar responses were observed during moderate exercise. In contrast, with metaboreflex activation during severe exercise, no further increases in CO or HR occurred, the increases in MAP and CBF were attenuated, and a significant reduction in CVC was observed (1.00 ± 0.12 vs. 0.90 ± 0.13 ml · min−1 · mmHg−1; P < 0.05). Similarly, when the metaboreflex was activated during mild exercise with the rise in cardiac work lessened (via constant HR and β1-blockade), no increase in CO occurred, the MAP and CBF responses were attenuated (+15.6 ± 4.5 mmHg, +8.3 ± 2 ml/min), and CVC significantly decreased from 0.63 ± 0.11 to 0.53 ± 0.10 ml · min−1 · mmHg−1. We conclude that the muscle metaboreflex induced increases in sympathetic nerve activity to the heart functionally vasoconstricts the coronary vasculature.

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

2006 ◽  
Vol 101 (1) ◽  
pp. 14-22 ◽  
Author(s):  
Robert A. Augustyniak ◽  
Eric J. Ansorge ◽  
Jong-Kyung Kim ◽  
Javier A. Sala-Mercado ◽  
Robert L. Hammond ◽  
...  
Keyword(s):  
Heart Failure ◽  
Skeletal Muscle ◽  
Treadmill Exercise ◽  
Cardiovascular Responses ◽  
Moderate Exercise ◽  
Muscle Metaboreflex ◽  
Blood Flows ◽  
Graded Exercise ◽  
Rapid Ventricular Pacing ◽  
Chronically Instrumented Dogs

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.

scholarly journals Muscle metaboreflex improves O2delivery to ischemic active skeletal muscle

1999 ◽  
Vol 276 (4) ◽  
pp. H1399-H1403 ◽  
Author(s):  
Donal S. O’Leary ◽  
Robert A. Augustyniak ◽  
Eric J. Ansorge ◽  
Heidi L. Collins
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Pressor Response ◽  
Systemic Arterial Pressure ◽  
Integrative Approach ◽  
Muscle Metaboreflex ◽  
Arterial Blood ◽  
Per Se ◽  
Hb Concentration ◽  
Ischemic Muscle

Ischemia of active skeletal muscle elicits a powerful pressor response, termed the muscle metaboreflex. We recently reported that the muscle metaboreflex pressor response acts to partially restore blood flow to the ischemic active skeletal muscle. However, because this reflex is activated by reductions in O2 delivery rather than blood flow per se, gain of the muscle metaboreflex as analyzed on the basis of blood flow alone may underestimate its true strength if this reflex also acts to increase arterial O2content. In conscious dogs chronically instrumented to measure systemic arterial pressure, cardiac output, and hindlimb blood flow, we activated the muscle metaboreflex via graded, partial reductions in hindlimb blood flow during mild (3.2 km/h) and moderate (6.4 km/h, 10% grade) workloads. At rest, during free-flow exercise, and with metaboreflex activation, we analyzed arterial blood samples for Hb concentration and O2 content and compared muscle metaboreflex gain calculations based on the ability to partially restore flow with those based on the ability to partially restore O2 delivery (blood flow × arterial O2 content). During both mild and moderate exercise, metaboreflex activation caused significant increases in arterial Hb concentration and O2 content. Metaboreflex gain quantified on the ability to partially restore O2 delivery was significantly greater than that based on restoration of blood flow during both mild and moderate workloads (0.52 ± 0.10 vs. 0.39 ± 0.08, P < 0.05, and 0.61 ± 0.05 vs. 0.46 ± 0.04, P < 0.05, respectively). We conclude that the muscle metaboreflex acts to increase both arterial O2 content and blood flow to ischemic muscle such that when combined, O2 delivery is substantially increased and metaboreflex gain is greater when analyzed with a more integrative approach.

scholarly journals Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow

2016 ◽  
Vol 311 (5) ◽  
pp. H1268-H1276 ◽  
Author(s):  
Jasdeep Kaur ◽  
Alberto Alvarez ◽  
Hanna W. Hanna ◽  
Abhinav C. Krishnan ◽  
Danielle Senador ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Arterial Pressure ◽  
Pressor Response ◽  
Muscle Blood Flow ◽  
Arterial Baroreflex ◽  
Muscle Metaboreflex ◽  
Peripheral Vasoconstriction ◽  
Bilateral Carotid ◽  
Ischemic Muscle

The muscle metaboreflex and arterial baroreflex regulate arterial pressure through distinct mechanisms. During submaximal exercise muscle metaboreflex activation (MMA) elicits a pressor response virtually solely by increasing cardiac output (CO) while baroreceptor unloading increases mean arterial pressure (MAP) primarily through peripheral vasoconstriction. The interaction between the two reflexes when activated simultaneously has not been well established. We activated the muscle metaboreflex in chronically instrumented canines during dynamic exercise (via graded reductions in hindlimb blood flow; HLBF) followed by simultaneous baroreceptor unloading (via bilateral carotid occlusion; BCO). We hypothesized that simultaneous activation of both reflexes would result in an exacerbated pressor response owing to both an increase in CO and vasoconstriction. We observed that coactivation of muscle metaboreflex and arterial baroreflex resulted in additive interaction although the mechanisms for the pressor response were different. MMA increased MAP via increases in CO, heart rate (HR), and ventricular contractility whereas baroreflex unloading during MMA caused further increases in MAP via a large decrease in nonischemic vascular conductance (NIVC; conductance of all vascular beds except the hindlimb vasculature), indicating substantial peripheral vasoconstriction. Moreover, there was significant vasoconstriction within the ischemic muscle itself during coactivation of the two reflexes but the remaining vasculature vasoconstricted to a greater extent, thereby redirecting blood flow to the ischemic muscle. We conclude that baroreceptor unloading during MMA induces preferential peripheral vasoconstriction to improve blood flow to the ischemic active skeletal muscle.

Regulation of the Circulation During Exercise

1956 ◽  
Vol 184 (3) ◽  
pp. 613-623 ◽  
Author(s):  
A. C. Barger ◽  
V. Richards ◽  
J. Metcalfe ◽  
B. Günther
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Oxygen Consumption ◽  
Steady State ◽  
Rest Period ◽  
Moderate Exercise ◽  
Work Intensity ◽  
Short Bout ◽  
Graded Exercise ◽  
Oxygen Difference

Oxygen consumption and cardiac output (direct Fick) have been measured in normal dogs at rest and during graded exercise on the treadmill up to a work intensity of 5 mph and 10°. Systemic and pulmonary artery pressures have also been recorded. The changes in cardiac output produced ‘at rest’ by excitement were frequently as large as those induced by moderate exercise. A short bout of exercise followed by a rest period was far more efficacious in producing lower and more uniform results during rest and subsequent exercise than a prolonged rest period alone. Under such conditions the ‘steady state’ was reached in 3 minutes or less of exercise. The linear relation between oxygen consumption and cardiac output during exercise in the dog is similar to that observed in man, and in the horse. The possible significance of this similarity is discussed and it is suggested that the data are consistent with the hypothesis that the increase in blood flow during exercise is largely the increase in muscle flow with a constant arteriovenous oxygen difference of approximately 14 vol. %.

Ventricular volume overload alters cardiac output distribution in rats during exercise

1980 ◽  
Vol 49 (3) ◽  
pp. 482-490 ◽  
Author(s):  
S. F. Flaim ◽  
W. J. Minteer
Keyword(s):  
Skeletal Muscle ◽  
Cardiac Output ◽  
Left Ventricular Volume ◽  
Treadmill Exercise ◽  
Volume Overload ◽  
Ventricular Volume ◽  
Major Effect ◽  
Left Ventricular ◽  
Radioactive Microsphere ◽  
Radioactive Microsphere Technique

A rat model for chronic left ventricular volume overload (a-v fistula, 2 mo) was used to test the effects of acute exhaustive treadmill exercise (EX) (5 min, 70 ft/min, 0 degrees grade) on cardiocirculatory hemodynamics and cardiac output (CO) distribution during heart failure (HF). Control (C) and HF rats were studied at rest (R) and during the last minute of EX. Heart rate (HR), mean arterial pressure (MAP), and left ventricular end-diastolic (LVEDP) pressure were recorded and CO, blood flow (BF) to various regions, and total CO distribution were determined by the radioactive microsphere technique. In HF, biventricular hypertrophy and elevated LVEDP at R were correlated with an average shunt size equaling 37% of total CO. In both groups, CO and HR rose during EX with no change in MAP. Systemic CO in HF was reduced compared to C during both R and EX. BF to splanchnic, renal, cutaneous, and testicular circulations was compromised at R in HF, whereas only skeletal muscle BF was compromised in HF during EX. Data for CO distribution suggest that the major effect of HF during R was increased delivery to the coronary and the skeletal muscle beds at the expense of the cutaneous and renal beds, whereas %CO to the cerebral, hepatic, and gastrointestinal beds was spared. During EX, %CO to skeletal muscle beds in HF was attenuated compared to C, whereas that to the coronary bed was increased with no change in other regions.

scholarly journals Muscle metaboreflex-induced coronary vasoconstriction functionally limits increases in ventricular contractility

2010 ◽  
Vol 109 (2) ◽  
pp. 271-278 ◽  
Author(s):  
Matthew Coutsos ◽  
Javier A. Sala-Mercado ◽  
Masashi Ichinose ◽  
ZhenHua Li ◽  
Elizabeth J. Dawe ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Output ◽  
Left Ventricular ◽  
Ventricular Contractility ◽  
Left Ventricular Contractility ◽  
Coronary Vasodilation ◽  
Cardiac Work ◽  
Vascular Conductance ◽  
Muscle Metaboreflex ◽  
Coronary Vasoconstriction

Muscle metaboreflex activation during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility, and afterload. This increase in cardiac work should cause coronary metabolic vasodilation. However, little if any coronary vasodilation is observed due to concomitant sympathetically induced coronary vasoconstriction. The purpose of the present study is to determine whether the restraint of coronary vasodilation functionally limits increases in left ventricular contractility. Using chronically instrumented, conscious dogs ( n = 9), we measured mean arterial pressure, cardiac output, and circumflex blood flow and calculated coronary vascular conductance, maximal derivative of ventricular pressure (dp/d tmax), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2 mph) before and during activation of the muscle metaboreflex. Experiments were repeated after systemic α1-adrenergic blockade (∼50 μg/kg prazosin). During prazosin administration, we observed significantly greater increases in coronary vascular conductance (0.64 ± 0.06 vs. 0.46 ± 0.03 ml·min−1·mmHg−1; P < 0.05), circumflex blood flow (77.9 ± 6.6 vs. 63.0 ± 4.5 ml/min; P < 0.05), cardiac output (7.38 ± 0.52 vs. 6.02 ± 0.42 l/min; P < 0.05), dP/d tmax (5,449 ± 339 vs. 3,888 ± 243 mmHg/s; P < 0.05), and PRSW (160.1 ± 10.3 vs. 183.8 ± 9.2 erg·103/ml; P < 0.05) with metaboreflex activation vs. those seen in control experiments. We conclude that the sympathetic restraint of coronary vasodilation functionally limits further reflex increases in left ventricular contractility.

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