The acute inotropic effects of cardiac contractility modulation (CCM) are associated with action potential duration shortening and mediated by β1-adrenoceptor signalling

Myocardial contractile dysfunction develops following trauma-hemorrhagic shock (T/HS). We have previously shown that, in a rat fixed pressure model of T/HS (mean arterial pressure of 30–35 mmHg for 90 min), mesenteric lymph duct ligation before T/HS prevented T/HS-induced myocardial contractile depression. To determine whether T/HS lymph directly alters myocardial contractility, we examined the functional effects of physiologically relevant concentrations of mesenteric lymph collected from rats undergoing trauma-sham shock (T/SS) or T/HS on both isolated cardiac myocytes and Langendorff-perfused whole hearts. Acute application of T/HS lymph (0.1–2%), but not T/SS lymph, induced dual inotropic effects on myocytes with an immediate increase in the amplitude of cell shortening (1.4 ± 0.1-fold) followed by a complete block of contraction. Similarly, T/HS lymph caused dual, positive and negative effects on cellular Ca2+ transients. These effects were associated with changes in the electrophysiological properties of cardiac myocytes; T/HS lymph initially prolonged the action potential duration (action potential duration at 90% repolarization, 3.3 ± 0.4-fold), and this was followed by a decrease in the plateau potential and membrane depolarization. Furthermore, intravenous infusion of T/HS lymph, but not T/SS lymph, caused myocardial contractile dysfunction at 24 h after injection, which mimicked actual T/HS-induced changes; left ventricular developed pressure (LVDP) and the maximal rate of LVDP rise and fall (±dP/d tmax) were decreased and inotropic response to Ca2+ was blunted. However, the contractile responsiveness to β-adrenergic receptor stimulation in the T/HS lymph-infused hearts remained unchanged. These results suggest that T/HS lymph directly causes negative inotropic effects on the myocardium and that T/HS lymph-induced changes in myocyte function are likely to contribute to the development of T/HS-induced myocardial dysfunction.

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Positive inotropic effect of acetylcholine in canine cardiac Purkinje fibers

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1985.249.4.h735 ◽

1985 ◽

Vol 249 (4) ◽

pp. H735-H740 ◽

Cited By ~ 3

Author(s):

R. F. Gilmour ◽

D. P. Zipes

Keyword(s):

Action Potential ◽

Action Potential Duration ◽

Force Transducer ◽

Resting Membrane Potential ◽

Inotropic Effects ◽

Purkinje Fibers ◽

Cardiac Purkinje Fibers ◽

High Concentrations ◽

Dose Dependent Increase

The purpose of this study was to investigate possible mechanisms to explain the positive inotropic effects of acetylcholine in canine cardiac Purkinje fibers. Action potentials and tension were recorded from Purkinje fibers in vitro using microelectrodes and a force transducer. Acetylcholine (10(-9) to 10(-4) M) produced a dose-dependent increase in tension that was blocked by atropine but not by propranolol, phentolamine, hexamethonium, or verapamil. At 10(-5) and 10(-4) M, acetylcholine increased action potential duration at 50% of repolarization (APD50) but did not affect resting membrane potential, action potential amplitude, Vmax, or action potential duration at 90% of repolarization (APD90). Isoproterenol (10(-7) M) shortened APD50 and APD90 and increased developed tension. Subsequent addition of acetylcholine (10(-5) M) prolonged APD50 and APD90 and decreased tension. Increasing extracellular Ca2+ concentration [( Ca2+]o) from 2.0 to 3.0 mM increased tension and shortened APD50. Addition of acetylcholine (10(-5) M) increased tension further and prolonged APD50. In K+-depolarized fibers high concentrations of acetylcholine (10(-4) M) restored excitability, but lower concentrations (10(-6) M) suppressed slow responses induced by isoproterenol. Thus acetylcholine alone or with elevated [Ca2+]o increased APD50 and tension and facilitated the induction of slow responses, yet in the presence of isoproterenol acetylcholine increased APD50, decreased tension, and suppressed slow responses. These effects were mediated by muscarinic receptors and were independent of catecholamine release.

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Pathophysiological role of major adipokines in Atrial Fibrillation

International Journal of Arrhythmia ◽

10.1186/s42444-021-00048-6 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Saira Rafaqat ◽

Sana Rafaqat ◽

Simon Rafaqat

Keyword(s):

Atrial Fibrillation ◽

Action Potential ◽

Action Potential Duration ◽

Cardiac Contractility ◽

Left Ventricular ◽

Review Article ◽

Atrial Remodeling ◽

Main Body ◽

Tnf Α ◽

Pathophysiological Role

Abstract Background The adipokines, secreted from adipose tissue or body fats, are also called adipocytokines which are cytokines, cell signaling proteins or cell–cell communication. However, AF is a common cardiac arrhythmia in which the heart beats so fast by abnormal beating and is a serious public health disease associated with increased heart failure, systemic thromboembolism, and death. Adipokines are cardiovascular disease (CVD) mediators or biomarkers that affect the heart as well as blood vessels, by increasing the cardiac contractility and action potential duration, which result in the extent of left ventricular and atrial remodeling. Main body Google Scholar, PubMed, and science direct were used to review the literature. Many keywords were used for searching the literature such as Adipokines, Leptin, Apelin, Adiponectin, Omentin-1, Chemerin, CTRP3, TNF-α, IL-6, IL-10, and AF. According to the literature, much more data are available for numerous adipokines, but this review article only has taken few major adipokines which played their major role in Atrial Fibrillation. The review article did not limit the time frame. Conclusion In conclusion, adipokines play a significant role in the development and progress of atrial fibrillation. Also, there are major adipokines such as adiponectin, apelin, C1q/TNF-Related Protein 3 (CTRP3), Chemerin, Omentin-1, interleukin-6, Leptin, TNF-α, resistin, and interleukin-10, which played their pathophysiological role in atrial fibrillation by causing cardiac hypertrophy, increasing the cardiac contractility and action potential duration, atrial fibrosis, electrical and structural remodeling of atrial tissue.

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Dual effects of mesenteric lymph isolated from rats with burn injury on contractile function in rat ventricular myocytes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00808.2005 ◽

2006 ◽

Vol 290 (2) ◽

pp. H778-H785 ◽

Cited By ~ 4

Author(s):

Atsuko Yatani ◽

Da-Zhong Xu ◽

Keiichi Irie ◽

Kazunori Sano ◽

Anoush Jidarian ◽

...

Keyword(s):

Action Potential ◽

Action Potential Duration ◽

Burn Injury ◽

Ventricular Myocytes ◽

Contractile Dysfunction ◽

Inotropic Effects ◽

Rat Ventricular Myocytes ◽

Mesenteric Lymph ◽

Action Potential Plateau ◽

Potential Plateau

Gut-derived factors in intestinal lymph have been shown to trigger myocardial contractile dysfunction. However, the underlying cellular mechanisms remain unclear. We examined the effects of physiologically relevant concentrations of mesenteric lymph collected from rats with 40% burn injury (burn lymph) on excitation-contraction coupling in rat ventricular myocytes. Burn lymph (0.1–5%), but not control mesenteric lymph from sham-burn animals, induced dual positive and negative inotropic effects depending on the concentrations used. At lower concentrations (<0.5%), burn lymph increased the amplitude of myocyte contraction (1.6 ± 0.3-fold; n = 12). At higher concentrations (>0.5%), burn lymph initially enhanced myocyte contraction, which was followed by a block of contraction. These effects were partially reversible on washout. The initial positive inotropic effect was associated with a prolongation of action potential duration (measured at 90% repolarization, 2.5 ± 0.6-fold; n = 10), leading to significant increases in the net Ca2+ influx (1.7 ± 0.1-fold; n = 8). There were no significant changes in the resting membrane potential. The negative inotropic effect was accompanied by a decrease in the action potential plateau (overshoot decrease by 69 ± 10%; n = 4) and membrane depolarization. Voltage-clamp experiments revealed that the positive inotropic effects of burn lymph were due to an inhibition of the transient outward K+ currents that prolong action potential duration, and the inhibitory effects were due to a concentration-dependent inhibition of Ca2+ currents that lead to a reduction of action potential plateau. These burn lymph-induced changes in cardiac myocyte Ca2+ handling can contribute to burn-induced contractile dysfunction and ultimately to heart failure.

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