Laudi S, Weimann J, Haschke M, Trump S, Schmitz V, Christians U, Kaisers U, Steudel W
Department of Anesthesiology, Perioperative Care and Pain Medicine, University of Colorado, Health Sciences Center, Denver, Colorado, USA.
J Physiol Pharmacol. 2007 Mar;58(1):19-32.
Pretreatment with cyclosporine (CsA) decreases infarct size 24h after myocardial ischemia/reperfusion (I/R). The goal of this study was to determine effects of CsA pretreatment on long-term cardiac function after I/R-injury. Rats were randomly assigned to group-1: vehicle-only, group-2: CsA-5mg/kg/day, and group-3: CsA-12.5mg/kg/day given orally for three days prior to I/R-injury (30 min of left anterior descending coronary artery occlusion). Post-I/R survival and cardiac function were evaluated 14 days after I/R-injury by echocardiography and invasive hemodynamic measurements. Rats with I/R-injury showed increased left ventricular pressure (LVEDP) compared to rats without I/R-injury (p<0.005). Although CsA initially decreased infarct size, no differences of LVEDP were seen 14 days after I/R-injury (vehicle: 21.2+/-8.9 mmHg, CsA-5mg/kg/day: 21.5+/-0.7 mmHg, CsA-12.5mg/kg/day: 20.5+/-9.4 mmHg). Ejection fraction and fractional shortening were decreased compared to baseline, but showed no differences between groups. On day 14, a dose-dependent increase in left ventricular end diastolic diameter was seen (p<0.001). CsA pretreatment was associated with a dose-dependent decrease in post-I/R-survival (vehicle: 56%, CsA-5mg/kg/day: 32%, CsA-12.5mg/kg/day: 16%; p=0.017). CsA pretreatment did not improve long-term cardiac function despite decreased infarct size 24h after I/R-injury, but increased post-I/R mortality significantly. Poor cardiac function after CsA pretreatment might be caused by left ventricular dilation.
用环孢素（CsA）预处理可减小心肌缺血/再灌注（I/R）24小时后的梗死面积。本研究的目的是确定CsA预处理对I/R损伤后长期心脏功能的影响。将大鼠随机分为1组：仅给予赋形剂；2组：给予5mg/kg/天的CsA；3组：给予12.5mg/kg/天的CsA，在I/R损伤（左冠状动脉前降支闭塞30分钟）前连续三天口服给药。在I/R损伤14天后，通过超声心动图和有创血流动力学测量评估I/R后的生存率和心脏功能。与未发生I/R损伤的大鼠相比，发生I/R损伤的大鼠左心室压力（LVEDP）升高（p<0.005）。尽管CsA最初减小了梗死面积，但在I/R损伤14天后未观察到LVEDP的差异（赋形剂组：21.2±8.9 mmHg，CsA 5mg/kg/天组：21.5±0.7 mmHg，CsA 12.5mg/kg/天组：20.5±9.4 mmHg）。与基线相比，射血分数和缩短分数降低，但各组之间无差异。在第14天，观察到左心室舒张末期直径呈剂量依赖性增加（p<0.001）。CsA预处理与I/R后生存率的剂量依赖性降低相关（赋形剂组：56%，CsA 5mg/kg/天组：32%，CsA 12.5mg/kg/天组：16%；p=0.017）。尽管CsA预处理在I/R损伤24小时后减小了梗死面积，但并未改善长期心脏功能，反而显著增加了I/R后的死亡率。CsA预处理后心脏功能不佳可能是由左心室扩张引起的。
