Muscle metaboreflex-induced coronary vasoconstriction limits ventricular contractility during dynamic exercise in heart failure

Coutsos, Matthew; Sala‐Mercado, Javier A.; Ichinose, Masashi; Li, Zhenhua; Dawe, Elizabeth J.; O’Leary, Donal S.

doi:10.1152/ajpheart.00879.2012

Cited by 38 publications

(80 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Inasmuch as the mechanisms mediating muscle metaboreflex-induced increases in arterial pressure are similar both during and immediately following (PEMI) submaximal dynamic exercise, these factors could contribute to the impaired maintenance of chronotropy, inotropy, and CO observed during PEMI in the present study. We previously demonstrated in normal subjects that metaboreflex-induced increases in sympathetic nerve activity vasoconstrict the coronary vasculature, thereby limiting the rise in coronary blood flow and impairing ventricular function (13) and that this coronary vasoconstriction is exaggerated in heart failure, which further exacerbates the ventricular dysfunction (14). To what extent metaboreflex activation during exercise in HTN leads to coronary vasoconstriction and impaired ventricular performance is unknown.…”

Section: Discussionmentioning

confidence: 99%

Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

Spranger

Kaur

Sala‐Mercado

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

DS. Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension. Am J Physiol Regul Integr Comp Physiol 308: R650 -R658, 2015. First published January 28, 2015 doi:10.1152/ajpregu.00464.2014.-During dynamic exercise, muscle metaboreflex activation (MMA; induced via partial hindlimb ischemia) markedly increases mean arterial pressure (MAP), and MAP is sustained when the ischemia is maintained following the cessation of exercise (postexercise muscle ischemia, PEMI). We previously reported that the sustained pressor response during PEMI in normal individuals is driven by a sustained increase in cardiac output (CO) with no peripheral vasoconstriction. However, we have recently shown that the rise in CO with MMA is significantly blunted in hypertension (HTN). The mechanisms sustaining the pressor response during PEMI in HTN are unknown. In six chronically instrumented canines, hemodynamic responses were observed during rest, mild exercise (3.2 km/h), MMA, and PEMI in the same animals before and after the induction of HTN [Goldblatt two kidney, one clip (2K1C)]. In controls, MAP, CO and HR increased with MMA (ϩ52 Ϯ 6 mmHg, ϩ2.1 Ϯ 0.3 l/min, and ϩ37 Ϯ 7 beats per minute). After induction of HTN, MAP at rest increased from 97 Ϯ 3 to 130 Ϯ 4 mmHg, and the metaboreflex responses were markedly attenuated (ϩ32 Ϯ 5 mmHg, ϩ0.6 Ϯ 0.2 l/min, and ϩ11 Ϯ 3 bpm). During PEMI in HTN, HR and CO were not sustained, and MAP fell to normal recovery levels. We conclude that the attenuated metaboreflex-induced HR, CO, and MAP responses are not sustained during PEMI in HTN.exercise pressor reflex; postexercise circulatory occlusion; peripheral resistance; hypertension THE MUSCLE METABOREFLEX IS a very powerful blood pressureraising reflex (1,3,12,22,42,48,51,65). Metabolically sensitive afferents of this reflex (group III/IV) are stimulated by metabolites (e.g., protons, lactate, potassium, and diprotonated phosphate), which accumulate within underperfused active skeletal muscle (10, 19, 30, 32, 35, 46, 47, 56 -58, 61). Muscle metaboreflex activation results in a reflex increase in sympathetic outflow (9, 28 -30, 36 -38, 62). During submaximal dynamic exercise, metaboreflex activation markedly increases heart rate (HR), cardiac output (CO) and left ventricular dP/dt max , with little effect on the peripheral vasculature (5,16,17,26,27,55,60,65). Therefore, the substantial metaboreflex-mediated pressor response observed during mild dynamic exercise is virtually solely the result of the increase in CO.In contrast, when metaboreflex activation is maintained following the cessation of submaximal dynamic exercise (postexercise muscle ischemia, PEMI) in normal subjects, the pressor response is sustained despite a decrease in HR toward resting levels with a time course similar to normal recovery from exercise (1,2,21,44,49,50,(62)(63)(64). The fall in HR during PEMI led some investigators to question the role of CO in mediating the sustained pressor response during PEMI (21,49,50,63)....

show abstract

Section: Discussionmentioning

confidence: 99%

Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

Spranger

Kaur

Sala‐Mercado

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

View full text Add to dashboard Cite

show abstract

“…In subjects with heart failure, the ability of the muscle metaboreflex to raise ventricular function is markedly diminished (18, 35). The reflex increases in cardiac output are much smaller, and despite modest increases in cardiac work (small increases in output pumped against elevated afterload), actual coronary vasoconstriction occurs (2,17). After ␣ 1 -adrenergic receptor blockade, this coronary vasoconstriction is reversed to vasodilation, the increases in coronary blood flow are much greater, and there is a partial return of ventricular function (17).…”

Section: Impaired Baroreflex Buffering Of Muscle Metaboreflex In Hearmentioning

confidence: 99%

“…The reflex increases in cardiac output are much smaller, and despite modest increases in cardiac work (small increases in output pumped against elevated afterload), actual coronary vasoconstriction occurs (2,17). After ␣ 1 -adrenergic receptor blockade, this coronary vasoconstriction is reversed to vasodilation, the increases in coronary blood flow are much greater, and there is a partial return of ventricular function (17). Thus the inability to raise cardiac output during metaboreflex activation in subjects with heart failure stems not only from the inherent ventricular dysfunction but also from accentuated coronary vasoconstriction that limits oxygen delivery to the myocardium, thereby limiting increases in cardiac function (17).…”

Section: Impaired Baroreflex Buffering Of Muscle Metaboreflex In Hearmentioning

confidence: 99%

“…However, in subjects with heart failure, the progressive increase in adrenergic drive produces a vicious cycle leading to deterioration of clinical status and eventually death. During submaximal dynamic exercise in these subjects, the muscle metaboreflex causes a reflex increase in sympathetic activity that, on its turn, causes accentuated coronary vasoconstriction, an important mechanism limiting the increased in ventricular function by reducing myocardial perfusion (17). Whether the respiratory metaboreflex is responsible for at least part of this increase in sympathetic drive causing coronary vasoconstriction is currently unknown.…”

Section: Metaboreflex Originating From Respiratory Musclesmentioning

confidence: 99%

See 1 more Smart Citation

Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex

Michelini

O’Leary

Raven

et al. 2015

American Journal of Physiology-Heart and Circulatory Physiology

Self Cite

View full text Add to dashboard Cite

Michelini LC, O'Leary DS, Raven PB, Nobrega AC. Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex*. Am J Physiol Heart Circ Physiol 309: H381-H392, 2015. First published May 29, 2015; doi:10.1152/ajpheart.00077.2015.-The last 100 years witnessed a rapid and progressive development of the body of knowledge concerning the neural control of the cardiovascular system in health and disease. The understanding of the complexity and the relevance of the neuroregulatory system continues to evolve and as a result raises new questions. The purpose of this review is to articulate results from studies involving experimental models in animals as well as in humans concerning the interaction between the neural mechanisms mediating the hemodynamic responses during exercise. The review describes the arterial baroreflex, the pivotal mechanism controlling mean arterial blood pressure and its fluctuations along with the two main activation mechanisms to exercise: central command (parallel activation of central somatomotor and autonomic descending pathways) and the muscle metaboreflex, the metabolic component of exercise pressor reflex (feedback from ergoreceptors within contracting skeletal muscles). In addition, the role of the cardiopulmonary baroreceptors in modulating the resetting of arterial baroreflex is identified, and the mechanisms in the central nervous system involved with the resetting of baroreflex function during dynamic exercise are also described. Approaching a very relevant clinical condition, the review also presents the concept that the impaired arterial baroreflex function is an integral component of the metaboreflex-mediated exaggerated sympathetic tone in subjects with heart failure. This increased sympathetic activity has a major role in causing the depressed ventricular function observed during submaximal dynamic exercise in these patients. The potential contribution of a metaboreflex arising from respiratory muscles is also considered. autonomic; baroreflex; central command; exercise; metaboreflex THIS ARTICLE is part of a collection on 1st Pan American Congress of Physiological Sciences: Physiology Without Borders. Other articles appearing in this collection, as well as a full archive of all collections, can be found online at http://ajpheart.physiology.org/.A wide range of complex but routine behaviors such as feeding, shivering, locomotion, aggressive/defensive, and sexual behaviors triggers concomitant activation of somatomotor and autonomic outflows (47). Dynamic exercise is a complex physiological challenge involving highly coordinated activity of skeletal muscles, rapid and immediate increases in respiratory function, heart rate (HR), stroke volume and cardiac output associated with changes in regional vascular resistance, and redistribution of systemic blood flow that cause a slight increase in mean blood pressure (108). The increased blood flow to active muscles provides the necessary o...

show abstract

“…In this case, heart rate (HR) would increase, but stroke volume (SV) would decrease, so CO would not increase as much during exercise. The SV decrease is related to impaired contractility and increased ventricular afterload sensitivity, whereby the ventricles become more sensitive to pressure changes [198,199]. An attenuation of the metaboreflex has also been found in hypertensive patients [200].…”

Section: Mechanism Of Action Of Tens On Hemodynamicsmentioning

confidence: 98%

Investigating Hemodynamic Responses to Electrical Neurostimulation

Youra¹

View full text Add to dashboard Cite

Investigating Hemodynamic Responses to Electrical Neurostimulation Sean YouraSince the 1900s, the number of deaths attributable to cardiovascular disease has steadily risen. With the advent of antihypertensive drugs and non-invasive surgical procedures, such as intravascular stenting, these numbers have begun to level off. Despite this trend, the number of patients diagnosed with some form of cardiovascular disease has only increased. By 2030, prevalence of coronary heart disease is expected to increase approximately by 18% in the United States. By 2050, prevalence of peripheral arterial occlusive disease is expected to increase approximately by 98% in the U.S. No single drug or surgical intervention offers a complete solution to these problems. Thus, a multifaceted regimen of lifestyle changes, medication, and device or surgical interventions is usually necessary. A potential adjunct therapy and cost-effective solution for treating cardiovascular disease that has been overlooked is neurostimulation.Recent studies show that using neurostimulation techniques, such as transcutaneous electrical nerve stimulation (TENS), can help to reduce ischemic pain, lower blood pressure, increase blood flow to the periphery, and decrease systemic vascular resistance. The mechanisms by which these hemodynamic changes occur is still under investigation. The primary aim of this thesis is to elucidate these mechanisms through a thorough synthesis of the existing literature on this subject. Neurostimulation, specifically TENS, is thought to modulate both the metaboreflex and norepinephrine release from sympathetic nerve terminals.To test the hypothesis that TENS increases local blood flow, decreases mean arterial pressure, and decreases cutaneous vascular resistance compared to placebo, in which the electrodes are attached but no electrical stimulation is applied, a protocol was developed to test the effect of neurostimulation on healthy subjects. Implementation of this protocol in a pilot study will determine if neurostimulation causes significant changes in blood flow using the most relevant perfusion measurement instrumentation. Before conducting this study, pre-pilot comparison studies of interferential current therapy (IFC) versus TENS, low frequency (4 Hz) TENS versus high frequency (100 Hz) TENS, and electrode placement on the back versus the forearm were conducted. The only statistically significant difference found was that the application of IFC on the back decreased the reperfusion time, meaning that the time required to reach the average baseline perfusion unit value after occlusion decreased. Further pre-pilot work investigating these different modalities and parameters is necessary to ensure that favorable hemodynamic changes can be detected in the pilot study.

show abstract

Muscle metaboreflex-induced coronary vasoconstriction limits ventricular contractility during dynamic exercise in heart failure

Cited by 38 publications

References 73 publications

Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

Attenuated muscle metaboreflex-induced pressor response during postexercise muscle ischemia in renovascular hypertension

Neural control of circulation and exercise: a translational approach disclosing interactions between central command, arterial baroreflex, and muscle metaboreflex

Investigating Hemodynamic Responses to Electrical Neurostimulation

Contact Info

Product

Resources

About