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

The studies described here investigate whether pathologic states that are t hought to cause myocardial damage through excess calcium entry (i.e., hypox ia and anoxia) indeed cause greater damage in hearts from ethanol-exposed a nimals, and whether L-type voltage-operated calcium channels (L-VOCCs) are implicated. Adult male Sprague-Dawley rats were exposed to intoxicating con centrations of ethanol vapor for 6-10 days, and their isolated hearts compa red with those of control animals in a Langendorff perfusion system. Hypoxi a was induced by perfusion with Krebs-Henseleit buffer, which had not previ ously been bubbled with oxygen; anoxia was produced by perfusion with buffe r bubbled with nitrogen. On reperfusion with oxygenated buffer, evidence of myocardial damage during the hypoxic/anoxic period was obtained by the rel ease of intracellular proteins into the perfusate. After hypoxia, release o f myoglobin (MYO) was significantly greater from hearts from ethanol-expose d rats than from controls; other indices of myocardial damage also were inc reased by hypoxia but did not differ significantly between treatment groups . After anoxic perfusion, release of lactate dehydrogenase (LDH) and creati ne phosphokinase (CPK) as well as MYO were all markedly and significantly i ncreased from ethanol-exposed hearts compared with those from control rats. The role of L-VOCCs in this damage was assessed with the calcium channel a ntagonist nitrendipine (10(-6) M) present in the perfusing buffer immediate ly before and during the anoxic stimulus. This completely reversed the situ ation so that preparations from ethanol-exposed rats now showed a reduced r elease of intracellular proteins compared with hearts from controls. Compar isons with absolute values from the previous experiments suggest that nitre ndipine increased release of LDH and CPK from control hearts with little ef fect 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 p athologic effects of hypoxia/anoxia in hearts from ethanol-exposed rats. Th is increased sensitivity may be at least partly a consequence of increased numbers of L-VOCCs in this tissue.