EFFECTS OF CHRONIC ETHANOL INGESTION ON CARDIAC ACTIONS OF ETHANOL AND COCAINE

乙醇与乙醇作用及相互作用的基本机制 可卡因对心脏的影响及其代谢物的可能作用 乙基可卡因，人们仍然知之甚少。更不知道的是 慢性酒精摄入对这些行为和相互作用的影响。 这项提议的目标是调查慢性酒精的影响。 乙醇和可卡因对心脏急性作用的摄取 单独或组合使用乙基可卡因。产仔的老鼠 等热量成对喂养两种不同的流质饮食方案30 将使用几周：不含乙醇的对照饮食，以及试验性饮食 含有乙醇的饮食。第三只小猫将被允许食用 固体和水是随意的。窦房准备与乳头肌 将从研究和实验动物中分离出来进行表演 平行实验。细胞内微电极将用于研究： (A)药物对窦房结自律性和房性的作用 和(B)其可能的抗心律失常或 行为。将研究乳头肌的变力作用。 力传感器。将利用特定的协议来研究 药物(A)对以恒定速度驱动的制剂的影响，以及 (B)关于力-间隔关系。具体的干预措施将是 用来探索乙醇、可卡因和 乙基可卡因处于不同变力状态或药物增强或 对特定细胞过程的抑制。收集到的数据将 提供有关慢性酒精摄取的影响的重要信息 乙醇、可卡因及其代谢物的急性作用 乙基可卡因。

The basic mechanisms of the actions and interactions of ethanol and cocaine on the heart, and the possible role of their metabolite ethylcocaine, are still poorly understood. Even less is known about the influence of chronic ethanol ingestion on these actions and interactions. The goal of this proposal is to investigate the effects of chronic ethanol ingestion on the acute in vitro cardiac actions on ethanol and cocaine alone, or in combination, and of ethylcocaine. Rat litter-mates isocalorically pair-fed two different regimens of a liquid diet for 30 weeks will be used: a control diet without ethanol, and an experimental diet containing ethanol. A third litter mate will be allowed to consume solid and water ad libitum. Sinoatrial preparations and papillary muscles will be isolated from the study and the experimental animals to perform parallel experiments. Intracellular microelectrodes will be used to study: (a) the actions of the drugs on sinus node automaticity and atrial and ventricular membrane potentials and (b) their possible anti-arrhythmic or actions. The inotropic actions will be studied in papillary muscles using a force transducer. Specific protocols will be utilized to study the effects of the drugs (a) on preparations driven at a constant rate, and (b) on the force-interval relationship. Specific interventions will be employed to probe the mechanisms of the actions of ethanol, cocaine, and ethylcocaine under different inotropic states or drug enhancement or inhibition of particular cellular processes. The data collected will provide important information on the effects of chronic ethanol ingestion on the acute actions of ethanol and cocaine, and their metabolite ethylcocaine.