缺血-再灌注不同时间点给予尼可地尔对犬心肌梗死范围的影响

目的　证实尼可地尔是通过激活心肌细胞 KATP通道而起到使梗死心肌范围明显缩小的作用 ;进一步了解在冠状动脉 (冠脉 )闭塞心肌缺血前后和再灌注时给予尼可地尔产生的心肌保护作用是否相同 ,为临床上应用 KATP通道开放剂防治急性心肌缺血性疾病提供依据。方法　 35条犬随机分为 5组 ,每组 7只。缺血再灌注组 (IR组 ) :冠脉左前降支 (L AD)闭塞 90 min,再灌注 12 0 min。缺血前给予尼可地尔组 (PNIC组 ) :L AD闭塞前 10 min经静脉给予尼可地尔 10 0μg/ kg,随后给予 10μg· kg- 1 · min- 1 持续静脉滴注至再灌注结束。缺血后 15 m in给予尼可地尔组 (INIC组 ) :L AD闭塞后 15 m in经静脉给尼可地尔 10 0μg/ kg,随后给予10 μg· kg- 1· min- 1持续至再灌注结束。再灌注开始时给予尼可地尔组 (RNIC组 ) :L AD闭塞 90 min,再灌注开始时立即静脉给尼可地尔 10 0 μg/ kg,随后给予 10 μg· kg- 1· m in- 1持续至再灌注结束。KATP通道阻滞剂组(GL IB+INIC组 ) :在 L AD闭塞前 10 min经静脉给予优降糖 0 .3m g/ kg 10 min,随后步骤同 INIC组。各组均在冠脉闭塞前、冠脉闭塞后 1h、再灌注 2 h测定血流动力学指标 ;再灌注 2 h后用图像分析仪测量氯化三苯四唑 (TTC)染色的梗死心肌范围 (IA)和危险心肌范围 (

Cardioprotective effects of KATP channel opener nicorandil during ischemia/reperfusion in dogs

OBJECTIVE: To further comfirm the effect of nicorandil in reducing the area of myocardial infarct is through the mediation of activation of the KATP channel but not by its nitrate-like properties, and to determine whether the protective effect is the same or not when the drug is either given immediate after infarction or after reperfusion. METHODS: Thirty-five dogs were randomly divided into five groups as follows. Ischemia/reperfusion (IR) group: the dogs were subjected to 90 minutes of left anterior descending coronary artery(LAD) occlusion followed by 120 minutes reperfusion. Pre-nicorandil (PNIC) group: nicorandil(NIC) 100 microg/kg was administrated by intravenous injection 10 minutes before occlusion, followed by infusion of 10 microg x kg(-1) x min (-1) of the drug till the end of reperfusion. Ischemia nicorandil(INIC) group: NIC 100 microg/kg was administered by intravenous injection 15 minutes after occlusion and 10 microg x kg(-1) x min (-1) of drug intravenously till the end of reperfusion. In the Onset reperfusion treated with nicorandil(RNIC) group: NIC 100 microg/kg was administered intravenously at the onset of reperfusion followed by 10 microg x kg(-1) x min (-1)of drug intravenously up to the end of reperfusion. Glibenclamide(GLIB)+INIC group: before NIC was administered, dogs were pretreated with GLIB 0.3 mg/kg for 10 minutes, and other treatment was the same as INIC group. Hemodynamics data were determined as baseline, 60 minutes post-occlusion, and 120 minutes post-reperfusion. By using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining, the infarct areas were analyzed with image analyzer. RESULTS: The results showed that at 60 minutes post-occlusion, cardiac output (CO) was reduced in every group compared with baseline (all P<0.01), CO value recovered at 120 minutes after reperfusion in both PNIC and INIC group (P>0.05). There were no significant differences in heart rate (HR), mean artery pressure(MAP), mean pulmonary artery pressure(MPAP), pulmonary capillary wedge pressure(PCWP) values among all the groups. A marked reduction in the infarct area was found in PNIC group and INIC group (P<0.01) compared with IR group. Administration of GLIB before INIC shows to have no protective effect (P>0.05). CONCLUSION: Our study shows that nicorandil which is a K ATP channel activator, could mimic the effect of ischemic pre-conditioning of the myocardium, by reducing the area of myocardial infarct.