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

本研究的目的是阐明Na（+）/H（+）交换抑制剂（NHEI）的副作用和最佳给药时间及给药方法。观察NHEI对心肌功能恢复的影响，并对左、右心室功能进行了观察。在使用冷晶体心脏停搏液进行长期心肌保存后，NHEI已被证明可以减少心脏的再灌注损伤。然而，全身给药可能会导致对中枢神经系统的不良影响。选择性冠状动脉内递送可以实现更高浓度的药剂，并且更小的药剂总剂量可以降低全身暴露和潜在的非靶器官毒性。以压力-容积关系评价左、右心室功能，作为评价心肌功能的可靠指标。将猪分配至四个研究组之一。第1组（n=6）供体动物在放血前10分钟给予NHEI（1 mg/kg）， ...更多信息 在心脏骤停后常温缺血30分钟后收集RTS。用冷Celsior溶液灌注心脏并原位移植。再灌注前10 min，体外循环回路中注入NHEI（2 mg/kg）。第2组（n=6）供体动物在放血前10分钟接受NHEI（1 mg/kg），并原位移植心脏。再灌注后选择性地将NHEI（6.7mg/kg/min）递送至冠状动脉30 min。第3组（n=6）供体动物在放血前10分钟接受NHEI（1 mg/kg），并原位移植心脏。再灌注后选择性地向冠状动脉输送NHEI（6.7mg/kg/min）10 min。第4组（n=6）供体动物在放血前10分钟接受生理盐水，心脏原位移植。再灌注前10 min，体外循环回路中注入NHEI（2 mg/kg）。心脏移植后，肺血管阻力升高，后负荷增加，但右心室容积在组1和2中保持不变。在第3组和第4组中，通过增加舒张末期容积（Frank-Starling机制）来维持后负荷增加期间的心输出量。结果表明，在组1和组2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并改善心肌保护。少

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