The effect of new drug delivery method on ventricular function after heart transplantation from non-heart-beating donors.

新的药物输送方法对无心跳供体心脏移植后心室功能的影响。

• 批准号: 15591463
• 负责人: IGUCHI Atsushi
• 金额: $ 2.24万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591463/
• 关键词: non-heart-beating donor; heart transplantation; conductance catheter; pressure-volume relation; left ventricular function; right ventricular function; ischemia reperfusion injury; sodium; hydrogen exchange; Na(+); H(+)交換抑制剤; 右心機能; 再灌流障害; 心保存

The purpose of present study was to elucidate the side effects and optimal timing and delivery method of Na(+)/H(+) exchange inhibitor (NHEI). Effect of NHEI on myocardial functional recovery was investigated and the function of both right ventricle and left ventricle was studied. After long-term myocardial preservation using cold crystalloid cardioplegic solution, NHEI has been demonstrated to reduce reperfusion injury of the heart. However, systemic drug delivery may lead to adverse effect on central nerves system. Selective intracoronary delivery can achieve higher concentrations of the agent and a smaller total dose of agent can be lowering systemic exposure and potential non-target organ toxicity. The function of right ventricle and left ventricle was assessed by pressure-volume relationship as a reliable measure of myocardial performance. Pigs were allocated to one of four study groups. In group 1 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hea … More rts were harvested after 30 min of normothermic ischernia following cardiac arrest. Hearts were perfused with cold Celsior solution and transplanted orthotopically. Ten minutes before reperfusion, NHEI (2 mg/kg) was injected to cardiopulmonary bypass circuit. In group 2 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hearts were transplanted orthotopically. NHEI (6.7 mg/kg/min) was selectively delivered to coronary artery for 30 minutes after reperfusion. In group 3 (n=6) donor animal received NHEI (1 mg/kg) 10 minutes before exanguination, and hearts were transplanted orthotopically. NHEI (6.7 mg/kg/min) was selectively delivered to coronary artery for 10 minutes after reperfusion. In group 4 (n=6) donor animal received saline 10 minutes before exanguination, and hearts were transplanted orthotopically. Ten minutes before reperfusion, NHEI (2 mg/kg) was injected to cardiopulmonary bypass circuit. After heart transplantation, pulmonary vascular resistance was elevated and afterload was increased, but right ventricular volume remained unchanged in groups 1 and 2. In groups 3 and 4, maintenance of the cardiac output during an increased afterload was obtained by an increased end-diastolic volume (Frank-Starling mechanism). It was demonstrated that in groups 1 and 2, the right ventricle maintains its output by improving its contractile performance. Selective intracoronary delivery can achieve lower systemic exposure and improved myocardial preservation. Less

本研究旨在阐明Na(+)/H(+)交换抑制剂(NHEI)的副作用及最佳给药时机和给药方法。观察NHEI对心肌功能恢复的影响以及对左、右室功能的影响。在使用冷晶体停搏液长期保存心肌后，NHEI已被证明可以减少心脏的再灌注损伤。然而，全身给药可能会对中枢神经系统产生不良影响。选择性冠状动脉内给药可以达到较高的药物浓度，较小的总剂量可以降低全身暴露和潜在的非靶器官毒性。右室和左室的功能通过压力-容量关系进行评估，作为心肌功能的可靠指标。猪被分配到四个研究组中的一个。第1组(n=6)供体动物在失血前10分钟给予NHEI(1 mg/kg)和Hea…。在心脏骤停后常温缺血30分钟后，收获更多的RTS。心脏用冷的Celsior液灌流，原位移植。再灌注前10min，体外循环循环中注入NHEI(2 mg/kg)。第2组(n=6)供体动物在放血前10min给予NHEI(1 mg/kg)，心脏原位移植。再灌流后选择性冠状动脉注射NHEI(6.7 mg/kg/min)30min。第3组(n=6)供体动物在放血前10min给予NHEI(1 mg/kg)，心脏原位移植。再灌流后选择性冠状动脉注射NHEI(6.7 mg/kg/min)10min。第4组(n=6)供体动物在放血前10min注射生理盐水，心脏原位移植。再灌注前10min，体外循环循环中注入NHEI(2 mg/kg)。心脏移植后，组1和组2肺血管阻力增加，后负荷增加，但右室容量不变。组3和组4通过增加舒张末容量维持心输出量(Frank-Starling机制)。结果表明，在第1组和第2组中，右心室通过改善其收缩性能来维持其输出。选择性冠状动脉内给药可降低全身暴露，改善心肌保护。较少