Myocardial mechanical, biochemical, and structural alterations induced by chronic ethanol ingestion in rats.

Abstract

To determine the effects of moderate ethanol consumption on the mechanical, biochemical, and structural characteristics of the heart, myocardial mechanical performance, contractile protein enzyme activity, and the number and size of myocytes were measured in male Fischer 344 rats after the ingestion of 30%o oral ethanol. Papillary muscles removed from the left ventricle were greater in length, weight, and crosssectional area than the corresponding muscles from the right side. However, no differences were found between control and ethanol-treated myocardium when either the left or right side was compared separately. Chronic ethanol ingestion resulted in an increase in resting tension in left ventricular muscles, with no alteration in peak developed tension. Moreover, time to peak tension was significantly prolonged, whereas a depression was observed in the peak rate of isometric tension development. Isotonically, left muscles from ethanol-treated rats revealed a prolongation of time to peak shortening and a marked depression in the velocity of shortening at physiological loads. No changes were noted in muscles from the right ventricle. Contractile protein enzyme activity revealed no differences in myofibrillar Mg2`-ATPase activity in right and left ventricular myocardium between control and ethanol-treated rats in the presence of EGTA. However, at physiological activating levels of calcium, an upward shift of the myofibrillar Mg2`-ATPase activity-calcium curve occurred in left myocardium, whereas a depression in this relation was seen in the right ventricle. As a result of chronic ethanol intake, a decrease was noted in the volume percent of myocardium occupied by myocytes, and that myocyte cell volume per nucleus was found to remain essentially constant throughout the various layers of the ventricular wall. Importantly, a 14% significant decrease in the total number of myocyte nuclei was demonstrated in the left ventricular myocardium of rats on chronic ethanol consumption. Thus, chronic but moderate alcohol ingestion resulted in depressed contractile performance, alterations in myofibrillar Mg2`-ATPase activity, and myocyte loss. These events may serve to function as preliminary indicators of the onset of heart failure of alcoholic origin in this animal model. (Circulation Research 1992;71:346-356

Physio-pathological effects of alcohol on the cardiovascular system: its role in hypertension and cardiovascular disease

“…36 Structural changes in cardiac muscle were also observed in heavy drinkers 37 as well as in ethanol-fed rats. 38 These changes may be involved in alcohol-induced cardiomyopathy, heart failure and arrhythmia.…”

Implantation of Immature Neonatal Cardiac Cells Into the Wall of the Aorta in Rats

“…force exerted by diastolic blood pressure (blood pressure in rats is Ϸ19Ϯ2.8/14Ϯ1.6 mN/mm 2 ). The size of the cuff of the cell grafts around the aorta in the present study was approximately the same as a rat papillary muscle, Ϸ8 mm in length with a cross-sectional area of Ϸ1 mm 2 and muscle weight of Ϸ10 mg, 18 which is the equivalent of Ϸ200 000 cardiomyocytes (there are Ϸ20 million cardiomyocytes in 1 g of heart tissue; therefore, 200 000 in 10 mg). The force produced by papillary muscles of rats (more than 20 mN/mm 2 ) 19,20 is considerably greater than that needed to overcome diastolic pressure.…”

“…The tension developed by right ventricular myocytes from rats is 39Ϯ2 mN/mm 2 measured in single skinned myocytes, 21 and in one study, developed tension of rat papillary muscles was as high as 60 mN/mm 2 . 18 Therefore, in theory, grafted aortic cardiac cells, once fully matured and connected, should be able to sustain enough force to contract the aorta in diastole. At least 200 000 surviving and functioning cardiomyocytes would be needed around the aorta to contract the aorta in diastole.…”

Restoration of YAP activation rescues HL-1 cardiomyocytes from apoptotic death by ethanol

“…In addition to its established deteriorating effect on the contractile ability of the heart and cardiomyocytes (Thomas et al, 1994), ethanol causes the death of cardiomyocytes: it has been reported that moderate but chronic (8 months) ethanol consumption results in the loss of ~14% myocytes in the hearts of rats (Capasso et al, 1992). Coincident with these observations, there are many reports showing that the direct exposure of cardiomyocytes to ethanol results in acute apoptotic cell death (Chen et al, 2000;Wang et al, 2015;Noritake et al, 2015).…”