Reffelmann Thorsten, Kloner Robert A
The Heart Institute, Good Samaritan Hospital, University of Southern California, 1225 Wilshire Boulevard, Los Angeles, CA 90017-2395, USA.
Cardiovasc Res. 2003 Aug 1;59(2):441-9. doi: 10.1016/s0008-6363(03)00435-8.
Adverse cardiac events in patients treated with the phosphodiesterase-5 inhibitor sildenafil for erectile dysfunction raised concerns about its safety in ischemic heart disease.
In anesthetized open-chest rabbits, receiving 1.45 mg/kg sildenafil intravenously or saline 30 min prior to ischemia (n=12, each), infarct size (IS, triphenyltetrazolium), the area of no-reflow (ANR, thioflavin S) (% of the risk area, RA, blue dye), and regional myocardial blood flow (RMBF, radioactive microspheres) were measured after 30 min of coronary occlusion and 180 min of reperfusion. Left ventricular hemodynamics and dimensions (echocardiography) were determined in a separate series of animals (n=5, each).
Sildenafil significantly lowered arterial blood pressure before occlusion (-17 to -19 mmHg over 30 min), but during ischemia and reperfusion hemodynamics were comparable to controls. IS in treated animals (51+/-4%) did not significantly differ from control animals (47+/-4%). No major arrhythmias or lengthening of QT/QTc occurred. While sildenafil slightly increased RMBF and significantly reduced specific vascular resistance in the RA during reperfusion (51+/-7 versus 73+/-10 mmHg g min/ml, P<0.05), the ANR (46+/-3%) was similar to control animals (44+/-4%). Sildenafil reduced left ventricular dP/dt(max) (P<0.05) and dP/dt(min) (P<0.01) in non-ischemic conditions, and slightly during ischemia, along with a pronounced decrease in ischemic left ventricular end-diastolic pressure (9+/-2 versus 15+/-2 mmHg after saline, P<0.05), but did not attenuate acute ischemic left ventricular dilation.
Sildenafil reduced cardiac pre- and afterload, and parameters of left ventricular contractility. Myocardial necrosis and microvascular dysfunction were neither exacerbated nor attenuated.
磷酸二酯酶5抑制剂西地那非用于治疗勃起功能障碍时，患者发生的不良心脏事件引发了对其在缺血性心脏病中安全性的担忧。
在麻醉开胸兔中，于缺血前30分钟静脉注射1.45毫克/千克西地那非或生理盐水（每组n = 12），在冠状动脉闭塞30分钟和再灌注180分钟后，测量梗死面积（IS，用三苯基四氮唑）、无复流面积（ANR，用硫黄素S）（占危险区[RA]的百分比，用蓝色染料）以及局部心肌血流量（RMBF，用放射性微球）。在另一组动物（每组n = 5）中测定左心室血流动力学和尺寸（超声心动图）。
西地那非在闭塞前显著降低动脉血压（30分钟内降低17至19毫米汞柱），但在缺血和再灌注期间血流动力学与对照组相当。治疗组动物的梗死面积（51±4%）与对照组动物（47±4%）无显著差异。未发生重大心律失常或QT/QTc延长。虽然西地那非在再灌注期间使局部心肌血流量略有增加，并显著降低了危险区的比血管阻力（51±7与73±10毫米汞柱·克·分钟/毫升，P<0.05），但无复流面积（46±3%）与对照组动物（44±4%）相似。西地那非在非缺血状态下降低左心室dP/dt（max）（P<0.05）和dP/dt（min）（P<0.01），在缺血期间略有降低，同时缺血左心室舒张末期压力显著降低（生理盐水注射后为15±2毫米汞柱，西地那非注射后为9±2毫米汞柱，P<0.05），但未减轻急性缺血性左心室扩张。
西地那非降低了心脏的前负荷和后负荷以及左心室收缩性参数。心肌坏死和微血管功能障碍既未加重也未减轻。
