Protective effects of ATP-sensitive potassium channel openes on ischemia/reperfusion injury in isolated rabbit hearts

Objective To investigate the protective effects of different ATP-sensitive potassium (K_ ATP) channel openers. Pinacidil and Diazoxide, on myocardium injury in isolated rabbit hearts caused by ischemia/reperfusion and the possible changes after application of ATP-sensitve potassium channel blocker, 5-HD. Methods Observation was made on rabbit hearts perfused with a Langendorff apparatus. Forty rabbits were randomly divided into five respective groups: 1. Pinacidil (Group P), 2. Diazoxide (Group D), 3. 5-HD+Pinacidil (Group HP), 4. 5-HD+Diazoxide (Group HD) and 5. the control (Group C). All groups were subjected to 40 minutes of occlusion, followed by 20 minutes of reperfusion as cardiac arrested by cold cardioplegia. Any one of Pinacidil, Diazoxide , Pinacidil or Diazoxide mixed with 5-HD was infused 15 minutes before cardioplegic heart rested in the experimental group. Cardiac tissue ultrastructure, hemodynamics variables, levels of adenine nucleotides and lipid peroxide of the myocardium were measured. Results (1) In Group P, Group D and Group HP, the recovery of myocardial contractility and heart rate after reperfusion was faster but MDA level and the amount of albumen released were lower than Group C. Moreover levels of myocardial adenosine triphosphate (ATP) were much higher compared with Group C. (2) In Group HP the recovery of myocardial contractility and heart rate was not as good as Group P, but its myocardium MDA level and amount of albumen released was higher than group P. Conclusion ATP-sensitive Potassium Channel openes may enhance myocardial protection against ischemia /reperfusion injury. The above effect of myocardial protection was only partially closed down by ATP-sensitive potassium channel blocker: 5-HD. The mitoK_ ATP channels on myocardium may be an important pathway of protection during ischemia/reperfusion process.