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

乙醇和乙醇的作用和相互作用的基本机理 可卡因对心脏的影响，以及其代谢产物的可能作用 乙基可卡因，仍然知之甚少。关于这一点，我们知道的更少。 慢性乙醇摄入对这些作用和相互作用的影响。 这项提案的目的是调查慢性乙醇的影响 摄入乙醇和可卡因对离体心脏的急性作用 单独或组合，以及乙基可卡因。同窝大鼠 等热量配对喂养两种不同的流质饮食方案， 周将被使用：不含乙醇的对照饮食和实验性饮食。 饮食中含有乙醇。第三个同窝出生的小伙伴 固体和水自由采食。窦房准备和乳头肌 将从研究和实验动物中分离出来， 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心房肌的作用， 心室膜电位和（B）它们可能的抗心肌梗塞或 行动将使用以下方法在乳头肌中研究变力作用 力传感器。将使用特定方案研究 药物（a）对以恒定速率驱动的制剂的影响，以及 (b)力与间隔的关系具体的干预措施将是 用于探索乙醇，可卡因和 乙基可卡因在不同的正性肌力状态或药物增强下，或 抑制特定的细胞过程。收集的数据将 提供关于长期摄入乙醇的影响的重要信息 对乙醇和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.