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

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

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00879.2012 ◽

2013 ◽

Vol 304 (7) ◽

pp. H1029-H1037 ◽

Cited By ~ 21

Author(s):

Matthew Coutsos ◽

Javier A. Sala-Mercado ◽

Masashi Ichinose ◽

ZhenHua Li ◽

Elizabeth J. Dawe ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Output ◽

Left Ventricular ◽

Dynamic Exercise ◽

Adrenergic Blockade ◽

Ventricular Contractility ◽

Cardiac Work ◽

Muscle Metaboreflex ◽

Coronary Vasoconstriction ◽

Before And After

Muscle metaboreflex activation (MMA) during dynamic exercise increases cardiac work and myocardial O2 demand via increases in heart rate, ventricular contractility, and afterload. This increase in cardiac work should lead to metabolic coronary vasodilation; however, no change in coronary vascular conductance occurs. This indicates that the MMA-induced increase in sympathetic activity to the heart, which raises heart rate, ventricular contractility, and cardiac output, also elicits coronary vasoconstriction. In heart failure, cardiac output does not increase with MMA presumably due to impaired ability to improve left ventricular contractility. In this setting actual coronary vasoconstriction is observed. We tested whether this coronary vasoconstriction could explain, in part, the reduced ability to increase cardiac performance during MMA. In conscious, chronically instrumented dogs before and after pacing-induced heart failure, MMA responses during mild exercise were observed before and after α1-adrenergic blockade (prazosin 20–50 μg/kg). During MMA, the increases in coronary vascular conductance, coronary blood flow, maximal rate of left ventricular pressure change, and cardiac output were significantly greater after α1-adrenergic blockade. We conclude that in subjects with heart failure, coronary vasoconstriction during MMA limits the ability to increase left ventricular contractility.

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Exaggerated coronary vasoconstriction limits muscle metaboreflex-induced increases in ventricular performance in hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00417.2016 ◽

2017 ◽

Vol 312 (1) ◽

pp. H68-H79 ◽

Cited By ~ 10

Author(s):

Marty D. Spranger ◽

Jasdeep Kaur ◽

Javier A. Sala-Mercado ◽

Abhinav C. Krishnan ◽

Rania Abu-Hamdah ◽

...

Keyword(s):

Blood Flow ◽

Ventricular Function ◽

Coronary Blood Flow ◽

Muscle Afferents ◽

Left Ventricular ◽

Adrenergic Blockade ◽

Ventricular Contractility ◽

Ventricular Performance ◽

Muscle Metaboreflex ◽

Coronary Vasoconstriction

Increases in myocardial oxygen consumption during exercise mainly occur via increases in coronary blood flow (CBF) as cardiac oxygen extraction is high even at rest. However, sympathetic coronary constrictor tone can limit increases in CBF. Increased sympathetic nerve activity (SNA) during exercise likely occurs via the action of and interaction among activation of skeletal muscle afferents, central command, and resetting of the arterial baroreflex. As SNA is heightened even at rest in subjects with hypertension (HTN), we tested whether HTN causes exaggerated coronary vasoconstriction in canines during mild treadmill exercise with muscle metaboreflex activation (MMA; elicited by reducing hindlimb blood flow by ~60%) thereby limiting increases in CBF and ventricular performance. Experiments were repeated after α1-adrenergic blockade (prazosin; 75 µg/kg) and in the same animals following induction of HTN (modified Goldblatt 2K1C model). HTN increased mean arterial pressure from 97.1 ± 2.6 to 132.1 ± 5.6 mmHg at rest and MMA-induced increases in CBF, left ventricular dP/d tmax, and cardiac output were markedly reduced to only 32 ± 13, 26 ± 11, and 28 ± 12% of the changes observed in control. In HTN, α1-adrenergic blockade restored the coronary vasodilation and increased in ventricular function to the levels observed when normotensive. We conclude that exaggerated MMA-induced increases in SNA functionally vasoconstrict the coronary vasculature impairing increases in CBF, which limits oxygen delivery and ventricular performance in HTN. NEW & NOTEWORTHY We found that metaboreflex-induced increases in coronary blood flow and ventricular contractility are attenuated in hypertension. α1-Adrenergic blockade restored these parameters toward normal levels. These findings indicate that the primary mechanism mediating impaired metaboreflex-induced increases in ventricular function in hypertension is accentuated coronary vasoconstriction. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/metaboreflex-induced-functional-coronary-vasoconstriction/ .

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Blood pressure reduction after gastric bypass surgery is explained by a decrease in cardiac output

Journal of Applied Physiology ◽

10.1152/japplphysiol.00362.2016 ◽

2017 ◽

Vol 122 (2) ◽

pp. 223-229 ◽

Cited By ~ 4

Author(s):

Peter M. van Brussel ◽

Bas van den Bogaard ◽

Barbara A. de Weijer ◽

Jasper Truijen ◽

C.T. Paul Krediet ◽

...

Keyword(s):

Blood Pressure ◽

Gastric Bypass ◽

Body Weight ◽

Cardiac Output ◽

Baroreflex Sensitivity ◽

Bypass Surgery ◽

Gastric Bypass Surgery ◽

Left Ventricular ◽

Ventricular Contractility ◽

Left Ventricular Contractility

Blood pressure (BP) decreases in the first weeks after Roux-and-Y gastric bypass surgery. Yet the pathophysiology of the BP-lowering effects observed after gastric bypass surgery is incompletely understood. We evaluated BP, systemic hemodynamics, and baroreflex sensitivity in 15 obese women[mean age 42 ± 7 standard deviation (SD) yr, body mass index 45 ± 6 kg/m2] 2 wk before and 6 wk following Roux-and-Y gastric bypass surgery. Six weeks after gastric bypass surgery, mean body weight decreased by 13 ± 5 kg (10%, P < 0.001). Office BP decreased from 137 ± 10/86 ± 6 to 128 ± 12/81 ± 9 mmHg ( P < 0.001, P < 0.01), while daytime ambulatory BP decreased from 128 ± 14/80 ± 9 to 114 ± 10/73 ± 6 mmHg ( P = 0.01, P = 0.05), whereas nighttime BP decreased from 111 ± 13/66 ± 7 to 102 ± 9/62 ± 7 mmHg ( P = 0.04, P < 0.01). The decrease in BP was associated with a 1.6 ± 1.2 l/min (20%, P < 0.01) decrease in cardiac output (CO), while systemic vascular resistance increased (153 ± 189 dyn·s·cm−5, 15%, P < 0.01). The maximal ascending slope in systolic blood pressure decreased (192 mmHg/s, 19%, P = 0.01), suggesting a reduction in left ventricular contractility. Baroreflex sensitivity increased from 9.0 [6.4–14.3] to 13.8 [8.5–19.0] ms/mmHg (median [interquartile range]; P < 0.01) and was inversely correlated with the reductions in heart rate ( R = −0.64, P = 0.02) and CO ( R = −0.61, P = 0.03). In contrast, changes in body weight were not correlated with changes in either BP or CO. The BP reduction following Roux-and-Y gastric bypass surgery is correlated with a decrease in CO independent of changes in body weight. The contribution of heart rate to the reduction in CO together with enhanced baroreflex sensitivity suggests a shift toward increased parasympathetic cardiovascular control. NEW & NOTEWORTHY The reason for the decrease in blood pressure (BP) in the first weeks after gastric bypass surgery remains to be elucidated. We show that the reduction in BP following surgery is caused by a decrease in cardiac output. In addition, the maximal ascending slope in systolic blood pressure decreased suggesting a reduction in left ventricular contractility and cardiac workload. These findings help to understand the physiological changes following gastric bypass surgery and are relevant in light of the increased risk of heart failure in these patients.

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Flow manipulation and the association with myocardial contractility during extracorporeal life support (FLAME)

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.030 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

SKT Ma ◽

WC Sin ◽

CW Ngai ◽

ASK Wong ◽

WM Chan ◽

...

Keyword(s):

Blood Flow ◽

Cardiogenic Shock ◽

Myocardial Contractility ◽

Life Support ◽

Extracorporeal Life Support ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

Ventricular Contractility ◽

Left Ventricular Contractility ◽

Extracorporeal Blood

Abstract Funding Acknowledgements Type of funding sources: None. Background Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is an advanced technique in extracorporeal life support (ECLS) used to support extreme circulatory failure including patients with cardiac arrest and cardiogenic shock refractory to conventional support. It is a long-standing belief that peripheral V-A ECMO poses increased afterload to the inured heart, but conventional echocardiographic measurements are often insensitive in detecting subtle changes in loading conditions. Purpose This study aimed to evaluate the effects of varying blood flow during peripheral V-A ECMO on intrinsic myocardial contractility, using detailed echocardiographic assessment including speckle tracking echocardiography (STE). Methods Adult patients with acute cardiogenic shock who were supported by peripheral V-A ECMO from April 2019 to September 2020 were recruited. Serial hemodynamic and cardiac performance parameters were measured by transthoracic echocardiogram (TTE) within 48 hours after implementation of V-A ECMO, at different levels of extracorporeal blood flow – 100%, 120% and 50% of target blood flow (TBF). Results A total of 30 patients were included. 22 (71%) were male, and the mean (SD) age was 54 (13) years. The major indications for V-A ECMO were myocardial infarction (19, 63% patients), and myocarditis (5, 17%). With a decrease in extracorporeal blood flow from 100% to 50% of TBF, mean arterial pressure (MAP) dropped from 76+/-3 to 64+/-3mmHg (p <0.001), and cardiac index (CI) increased from 0.89+/-0.13 to 1.27+/-0.18L/min/m2 (p < 0.001). All indices of left ventricular contractility improved at a lower extracorporeal blood flow: the myocardial contractility measured by global longitudinal peak systolic strain (GLPSS) improved from -3+/-0.7% to -5+/-0.8% (p < 0.001); left ventricular ejection fraction (LVEF) increased from 21.5+/-2.6% to 30.9+/-2.7% (p < 0.001) and 19.7+/-3.1% to 28.4+/-3.2% (p < 0.001) by biplane and linear methods, respectively; left ventricular index of myocardial performance (LIMP) improved from 1.51+/-0.12 to 1.03+/-0.09 (p < 0.001). Similar findings were reproduced when comparing left ventricular contractility at extracorporeal blood flows of 120% and 50% of TBF. Conclusions The ECMO blood flow rate in peripheral V-A ECMO is inversely related to myocardial contractility, and is quantifiable by myocardial strain measured by STE.

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Cardiovascular effects of the respiratory muscle metaboreflexes in dogs: rest and exercise

Journal of Applied Physiology ◽

10.1152/japplphysiol.00258.2003 ◽

2003 ◽

Vol 95 (3) ◽

pp. 1159-1169 ◽

Cited By ~ 55

Author(s):

Joshua R. Rodman ◽

Kathleen S. Henderson ◽

Curtis A. Smith ◽

Jerome A. Dempsey

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Lactic Acid ◽

Respiratory Muscle ◽

Cardiovascular Effects ◽

Cardiovascular Responses ◽

Vascular Conductance ◽

Iliac Arteries ◽

Muscle Metaboreflex ◽

Arterial Blood

In awake dogs, lactic acid was injected into the phrenic and deep circumflex iliac arteries to elicit the diaphragm and abdominal muscle metaboreflexes, respectively. At rest, injections into the phrenic or deep circumflex iliac arteries significantly increased mean arterial blood pressure 21 ± 7% and reduced cardiac output 6 ± 2% and blood flow to the hindlimbs 20 ± 9%. Simultaneously, total systemic, hindlimb, and abdominal expiratory muscle vascular conductances were reduced. These cardiovascular responses were not accompanied by significant changes in the amplitude or timing of the diaphragm electromyogram. During treadmill exercise that increased cardiac output, hindlimb blood flow, and vascular conductance 159 ± 106, 276 ± 309, and 299 ± 90% above resting values, lactic acid injected into the phrenic or deep circumflex iliac arteries also elicited pressor responses and reduced hindlimb blood flow and vascular conductance. Adrenergic receptor blockade at rest eliminated the cardiovascular effects of the respiratory muscle metaboreflex. We conclude that the cardiovascular effects of respiratory muscle metaboreflex activation are similar to those previously reported for limb muscles. When activated via metabolite production, the respiratory muscle metaboreflex may contribute to the increased sympathetic tone and redistribution of blood flow during exercise.

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Systemic and Coronary Haemodynamic Effects of the New Hypotensive Drug L 6150

Journal of International Medical Research ◽

10.1177/030006057600400605 ◽

1976 ◽

Vol 4 (6) ◽

pp. 402-409 ◽

Cited By ~ 8

Author(s):

Attilio Maseri ◽

Antonio Pesola ◽

Antonio L'Abbate ◽

Carlo Contini ◽

Glauco Magini

Keyword(s):

Blood Flow ◽

Cardiac Output ◽

Left Ventricular ◽

Haemodynamic Effects ◽

Coronary Resistance ◽

Coronary Vasodilation ◽

Hypotensive Drug ◽

Vasodilator Effect ◽

Coronary Vasodilator ◽

Oxygen Difference

The acute systemic and coronary haemodynamic effects of a new hypotensive drug L 6150 (3-hydrazino-6-[N,N-bis(2-hydroxyethyl)amino]pyridazine) have been studied in six patients with renal or essential hypertension. The drug, administered intravenously at a dose of 2-9 mg, caused a marked hypotension and increase of cardiac output in five cases. Though left ventricular work was reduced or unchanged after the drug, myocardial blood flow increased markedly, coronary resistance decreased and coronary A-V oxygen difference decreased by about 50% indicating coronary vasodilation. When compared with the available data on the effects of hydrazinophthalazine, L 6150 appeared to have qualitatively similar effects, but a somewhat greater direct coronary vasodilator effect.

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