Biphasic changes in cardiac excitation-contraction coupling early in chronic alcohol exposure

Abstract

Although the negative inotropic effects of both acute and chronic ethanol (EtOH) exposure are well known, little is known concerning the acute-to-chronic transition of such effects. In this study, our objective was to address this question by detailing the effects that acute EtOH exposure induces on cellular excitation-contraction (EC) coupling and, subsequently, comparing whether and how such changes translate to the early chronic EtOH condition in a rat model known to develop alcohol-induced cardiomyopathy. Acute EtOH exposure, as formerly reported, indeed induced dose-dependent negative inotropic changes in cellular EC coupling, manifest as reductions in cell shortening, Ca2+ transient amplitude, Ca2+ decay rate, and sarcoplasmic reticulum Ca2+ content of isolated rat ventricular cardiac myocytes. Supplementary to this, we found Ca2+ spark character not to be significantly affected by acute EtOH exposure. In contrast, the results obtained from cardiac myocytes isolated from rats fed a diet containing approximately 9% (vol/vol) EtOH for 1 mo revealed changes in these parameters reflecting positive inotropy, whereas at 3 mo, these parameters again reflected negative inotropy similar but not identical to that induced by acute EtOH exposure. No significant changes were evident at either 1- or 3-mo chronic EtOH administration in echocardiographic parameters known to be perturbed in alcoholic cardiomyopathy (ACM), thus indicating that we were examining an asymptomatic stage in chronic EtOH administration consistent with an acute-to-chronic transition phase. Continued study of such transition-phase events should provide important insight into which molecular-cellular components of EC coupling play pivotal roles in EtOH-induced disease processes, such as ACM.

Acute Alcohol Modulates Cardiac Function as PI3K/Akt Regulates Oxidative Stress

“…Alcohol-induced changes in the EF reflected changes in the SV, which was increased by LA and decreased by HA. Aistrup and colleagues (2006) have previously reported a decline in the excitation–contraction coupling associated with acute HA. In addition, it was recently shown in dogs (Fenelon et al, 2007) that acute EtOH depresses LV function.…”

Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart

“…Acetaldehyde is formed in cardiac I/R injury and during the metabolism of ethanol in the heart. The direct effects of acute acetaldehyde on the heart after 5–10 min exposure have been reported at least eight times 84–89 . Acetaldehyde causes vasoconstriction and positive inotropic and chronotropic responses at concentrations ≤3 mmol/L.…”

“…The direct effects of acute acetaldehyde on the heart after 5-10 min exposure have been reported at least eight times. [84][85][86][87][88][89] Acetaldehyde causes vasoconstriction and positive inotropic and chronotropic responses at concentrations £3 mmol ⁄ L. Levels >3 mmol ⁄ L induce cardiac dysfunction, vasodilation and hypotension. 90,91 The negative inotropy seen with these higher levels of acetaldehyde is associated with decreased release of Ca 2+ from the sarcoplasmic reticulum 86,87 and inhibition of voltage-dependent Ca 2+ channels.…”

ALDH2 in alcoholic heart diseases: Molecular mechanism and clinical implications

“…Acetaldehyde may trigger cardiac hypertrophy or dilated cardiomyopathy associated with a significant increase in the hypertrophic marker skeletal actin and ANF (Li & Ren, 2008; Liang et al, 1999). Direct effects of acute (5 to 10 min) acetaldehyde exposure on cardiovascular function have been extensively studied (Aberle & Ren, 2003; Aistrup et al, 2006; Brown et al, 1999, 2001; Brown & Savage 1996; Ren et al, 1997; Savage et al, 1995). Acetaldehyde produces vasoconstriction and positive inotropic and chronotropic responses at concentrations of 3 mM or below.…”