Suematsu Yoshihiro, Anttila Vesa, Takamoto Shinichi, del Nido Pedro
Department of Cardiac Surgery, Children's Hospital-Boston, Harvard Medical School, Boston, MA 02115, USA.
Scand Cardiovasc J. 2004 Oct;38(5):293-9. doi: 10.1080/14017430410021507.
The efficacy of ischemic preconditioning of the heart has remained controversial. We investigated whether chronic treatment with beta-blockers affects the ischemic preconditioning in the isolated rat heart model.
Wistar rats were treated with propranolol (50 mg/kg/day, p.o.) (PRL), with nipradilol (10 mg/kg/day, p.o.) (NPL), or with vehicle, for 4 weeks. Isolated rat hearts were divided into global ischemia hearts (GI, PRL and NPL, each n=6) and ischemic preconditioned hearts (IP, PRL+IP and NPL+IP, each n=6).
Significant differences in left ventricular pressure were observed between the PRL and PRL+IP, and between the NPL and NPL+IP groups. In the NPL group, significant amelioration and preservation of left ventricular peak pressure, coronary flow, reduction of infarct size, and NOx preservation were observed. Lipid peroxidation in the NPL group was significantly reduced before and after global ischemia compared to the GI group.
The effect of ischemic preconditioning was abolished in the hearts of rats following oral treatment of propranolol or nipradilol. However, the administration of nipradilol protected the ischemic and reperfused myocardium, partly due to the prevention of lipid peroxide formation.
心脏缺血预处理的疗效一直存在争议。我们研究了β受体阻滞剂的长期治疗是否会影响离体大鼠心脏模型中的缺血预处理。
将Wistar大鼠用普萘洛尔(50毫克/千克/天,口服)(PRL)、尼群地平(10毫克/千克/天,口服)(NPL)或赋形剂治疗4周。将离体大鼠心脏分为全心缺血心脏(GI,PRL组和NPL组,每组n = 6)和缺血预处理心脏(IP,PRL + IP组和NPL + IP组,每组n = 6)。
在PRL组与PRL + IP组之间以及NPL组与NPL + IP组之间观察到左心室压力存在显著差异。在NPL组中,观察到左心室峰值压力、冠状动脉血流量显著改善和保留,梗死面积减小,以及NOx保留。与GI组相比,NPL组在全心缺血前后脂质过氧化显著降低。
口服普萘洛尔或尼群地平后,大鼠心脏中缺血预处理的作用被消除。然而,尼群地平的给药保护了缺血再灌注心肌,部分原因是预防了脂质过氧化物的形成。