Increased sensitivity to damaging effects of hypoxia and anoxia of isolated hearts from rats after prolonged exposure to ethanol: Apparent protection by nitrendipine

The studies described here investigate whether pathologic states that are thought to cause myocardial damage through excess calcium entry (i.e., hypoxia and anoxia) indeed cause greater damage in hearts from ethanol-exposed animals, and whether L-type voltage-operated calcium channels (L-VOCCs) are implicated. Adult male Sprague-Dawley rats were exposed to intoxicating concentrations of ethanol vapor for 6-10 days, and their isolated hearts compared with those of control animals in a Langendorff perfusion system. Hypoxia was induced by perfusion with Krebs-Henseleit buffer, which had not previously been bubbled with oxygen; anoxia was produced by perfusion with buffer bubbled with nitrogen. On reperfusion with oxygenated buffer, evidence of myocardial damage during the hypoxic/anoxic period was obtained by the release of intracellular proteins into the perfusate. After hypoxia, release of myoglobin (MYO) was significantly greater from hearts from ethanol-exposed rats than from controls; other indices of myocardial damage also were increased by hypoxia but did not differ significantly between treatment groups. After anoxic perfusion, release of lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) as well as MYO were all markedly and significantly increased from ethanol-exposed hearts compared with those from control rats. The role of L-VOCCs in this damage was assessed with the calcium channel antagonist nitrendipine (10−6M) present in the perfusing buffer immediately before and during the anoxic stimulus. This completely reversed the situation so that preparations from ethanol-exposed rats now showed a reduced release of intracellular proteins compared with hearts from controls. Comparisons with absolute values from the previous experiments suggest that nitrendipine increased release of LDH and CPK from control hearts with little effect on these indices from ethanol-exposed hearts. However, in the case of anoxia-induced MYO release, nitrendipine markedly and significantly reduced this in hearts from ethanol-treated rats but had only a very small effect on the same parameter in controls. The results strongly suggest increased pathologic effects of hypoxia/anoxia in hearts from ethanol-exposed rats. This increased sensitivity may be at least partly a consequence of increased numbers of L-VOCCs in this tissue.