ADRENERGIC AGENTS FOR CARDIOPULMONARY RESUSCITATION

描述（改编自申请人摘要）：申请人声明 直到最近，心肺复苏术（CPR）的研究 主要集中在心脏复苏的初始阶段（第1阶段） 和治疗选择，通过这些治疗选择， 都恢复了 然而，申请人指出，临床和 实验观察表明心脏工作的实质性损害 心脏骤停复苏后的能力（第2阶段）;这可能 至少部分地解释了超过一半的死亡结果。 在心肺复苏术最初成功后的几小时和几天内， 本申请用于支持联合治疗的临床前研究。 肾上腺素能药物和缓冲剂对复苏后的影响 心肌功能和72小时存活率。 目标是定义 药理学支持的基本原理和优化， 立即复苏以及复苏后心室功能， 存活率和神经学结果得到改善。 肾上腺素能药物 使用的是肾上腺素后，其β 1-肾上腺素能作用已被阻断， 艾司洛尔。 缓冲剂将包括产生CO2的缓冲剂 （碳酸氢钠）和消耗CO2的有机缓冲剂（氨丁三醇）。 这些药物中的每一种分别对 复苏后心肌功能和存活率。 的 申请人建议扩展研究，以揭示 肾上腺素能和缓冲剂。 一种已建立的标准化啮齿动物 模型将被使用。 将诱导室颤， 在一段时间后尝试用电除颤复苏， 12或15分钟未经治疗的心脏骤停和额外的12分钟 “传统”CPR 复苏后心肌功能，神经系统 将比较恢复和存活时间。 复苏后 将根据心输出量的测量结果比较心肌功能 计算左心室每搏功、主动脉和右心房 左心室压力，计算冠状动脉灌注压 收缩压和舒张压、dP/dt 40、负dP/dt和负 dP/dt 50。

DESCRIPTION (adapted from the applicant's abstract): The applicant states that until recently, cardiopulmonary resuscitation (CPR) research has focused primarily on the initial stage of cardiac resuscitation (Stage 1) and therapeutic options by which a viable rhythm and spontaneous circulation are restored. However, the applicant indicates that both clinical and experimental observations indicate substantial impairment of cardiac work capability after resuscitation from cardiac arrest (Stage 2); this may explain, at least in part, the fatal outcome of more than one-half of patients in the early hours and days following the initial success of CPR. This application is for support of pre-clinical studies on the combined effects of adrenergic drugs and buffer agents on post-resuscitation myocardial function and 72 hour survival. The goal is to define the rationale for and optimization of pharmacological support such that not only immediate resuscitation but also post-resuscitation ventricular function, survival, and neurological outcome are improved. The adrenergic agent to be used is epinephrine after its beta1-adrenergic actions have been blocked by esmolol. The buffer agents will include a CO2 generating buffer agent (sodium bicarbonate) and a CO2 consuming organic buffer (tromethamine). Controlled experiments on the effects of each of these agents separately on post-resuscitation myocardial function and survival are proposed. The applicant proposes to extend studies such as to expose the combined effects of adrenergic and buffer agents. An established and standardized rodent model will be utilized. Ventricular fibrillation will be induced and resuscitation attempted with electrical defibrillation after an interval of either 12 or 15 minutes of untreated cardiac arrest and an additional 12 min of "conventional" CPR. Post-resuscitation myocardial function, neurological recovery and duration of survival will be compared. Post-resuscitation myocardial function will be compared based on measurements of cardiac output with computation of left ventricular stroke work, aortic and right atrial pressure with computation of coronary perfusion pressure, left ventricular systolic and diastolic pressures, dP/dt40, negative dP/dt, and negative dP/dt50.