The Protective Effect Of Mechanical And Pharmacological Postconditioning On Ischemia-reperfusion Injury And The Exploration For Its Mechanisms

Objective: The aims of this study were 1. To examine the cardioprotective effect of pharmacological postconditioning produced by a Na+/H +exchange inhibitor cariporide , and glutathione(GSH), a kind of antioxidant on ischemia reperfusion injury(IRI) .2. To find a best time window and a best effective pathway to perform the pharmacological postconditioning during the period of reperfusion using a new pathway of administration: left ventricular—aorta—coronary arteries. 3. To confirm the hypothesis that postconditioning has effect on ischemia reperfusion injury not at the first minute but the first half an hour during the period of reperfusion, and explores their different mechanisms. Methods: In anesthetized open-chest rats, the left anterior descending artery (LAD) was occluded for 30min and reperfused for 3h. The drugs for pharmacological postconditioning were a Na+/H +exchange inhibitor cariporide, and glutathione(GSH). The pathway of left ventricular—aorta—coronary arteries is in one minute administrating of GSH(120mg/kg) through the cannula of monitoring pressure. Results: 1.the protective effect of Cariporide and GSH on ischemia-reperfusion injury: Infarct size was less in the cariporide (37±5%)and GSH (39±2%) groups compared with control (52±1%). confirmed by plasma creatine kinase (CK) and malondialdehyde( MDA) activity after reperfusion(50±3U/ml ,3.4±2μmol/l;53±1U/ml ,3.6±0.4μmol/l vs.63 ±3U/ml,5.3±1.2μmol/l). 2.One part: Administering of GSH(120mg/kg) via left carotid artery—left ventricular—aorta—coronary arteries :in comparison with via the routine vein . Administering of GSH(120mg/kg) via left carotid artery—left ventricular—aorta—coronary arteries, plasma drug concentration of aorta (810±100μmol/l) was much more than via vein(351±50μmol/l). The other part: the protective effect on IRI via the new administering pathway. Infarct size was less via the left ventricular—aorta intervene group (23±4%)compared with via the vein group(39±2%). Plasma creatine kinase(CK) and malondialdehyde (MDA) activity was less after reperfusion in the group of administering of GSH(120mg/kg) via left carotid artery—left ventricular—aorta—coronary arteries(47±3 U/ml,3.2±1μmol/l) than via vein(53±1U/ml ,3.6±0.4μmol/l) . 3.Explore the mechanism of postconditioning at the onset of reperfusion. The kind of postconditioning model attenuated infarct size compared to control(34±4% vs. 52±1% in control),the protective effect was unaltered by 8-SPT(35±3%). Conclusion: 1.It is feasible by administering cariporide or GSH at the onset of reperfusion to protective myocardial IRI, which is pharmacological postconditioning .2. An available administration pathway via left ventricular—aorta—coronary arteries may increase plasma drug concentration of coronary artery.3. The cardioprotective effect produced by GSH via the administration pathway of left ventricular—aorta—coronary arteries is better remarkably than that via the routine venous pathway during the first 1 min of reperfusion. 4. postconditioning has effect on ischemia reperfusion injury not at the first minute but the first half an hour during reperfusion.