Studies On The Delayed Protection Of Buprenorphine And Nitroglycerin Used In Combination Against Myocardial Ischemia

The second window of preconditioning has a longer span of time and stronger cardioprotection than the acute ischemic preconditioning. Many drugs can initiate the mechanism of preconditioning, imitate ischemic preconditioning (IPC), namely pharmacological preconditioning (PPC). Our laboratory has demonstrated that nitroglycerol (NG) and buprenorphine (BU) could produce acute cardioprotection (the first window of protection) based on PPC. We further explored whether the two drugs can produce delayed protection (the second window of protection), and study the cardioprotection of intestinal short ischemia.52 healthy male Wistar rats were divided randomly into 5 groups and subjected to different treatments. After isolation of the anterior mesenteric artery, NS group:NS was administered iv in the same volume of agents; MIPC group: ligation of anterior mesenteric artery for lOmin; BU group: BU (l.Omg/kg) was administered iv; NG group:NG (0.3mg/kg) was administered iv; B+N group: BU and NG were given in the same doses as above. After 24h ,all rats were undergone 30min ischemia and followed by 2h reperfusion. Heart rate (HR), blood pressure (BP), ST- segment and arrhythmias were monitored continuously before and after medication, during the periods of ischemia and reperfusion. Plasma LDH and CK concentrations were measured before surgery, 15min after surgery, after 30min ischemia and after 2h reperfusion. HE and TTC stains were performed to determine the quality and quantity of myocardial necrosis after 2h reperfusion.The results were as follows: (1) Compared with NS group, MIPC group reduced ST- segment during ischemia (/><0.01), delayed the onset of ventricular premature contraction (VPC), shortened the duration of VPC (P<0.05), decreased the incidences of bigeminy, lowered the plasma LDHconcentration during ischemia (P<0.05), reduced the size of infarction (P<0.05), but could not reduce the incidences of ventricular tachycardia (VT) and ventricular fibrillation (VF). The improvement degree of the above indice was less than that of NG, BU and B+N group; (2) Compared with NS group, BU group reduced ST- segment during ischemia (P<0.01), delayed the onset of VPC, shortened the duration of VPC (P<0.05), decreased the incidences of bigeminy and VF (P<0.05), reduced the size of infarction, lowered the plasma LDH concentration during ischemia, reduced the necrosis of myocardium, but could not decrease the incidence of VT; (3) Compared with NS group, NG group reduced ST- segment during ischemia significantly (P<0.01), shortened the duration of VPC (<0.01), reduced the incidences of bigenimy, VT, VF (P<0.01), reduced the size of infarction significantly (P<0.01), reduced the necrosis of myocardium, but could not delay the onset of VPC; (4) B+N group reduced the ST- segment significantly (P<0.01, compared with NS group), decreased the incidences of bigenimy, VT, VF, reduced the size of infarction (P<0.001, compared with NS group), lowered the level of LDH in plasma (P<0.001, compared with NS group). All groups could not reduce the level of CK in plasma.It is concluded that BU and NG used alone or in combination can produce the second window of protection in rats and the combination is superior to the alone. The study provides experimental support for the combined use of BU and NG against ischemia-reperfusion injury. Anterior mesenteric artery ischemia for lOmin has less strong cardioprotection, which is probably related to short ischemia.