Objective: To investigate the effectiveness of pinacidil, an opener of ATP-sensitive K+ channels, in protecting the myocardium of immature rabbit hearts from ischemic reperfusion injury.
Methods: Rabbit hearts underwent 30 min of global normothermic ischemia followed by 30 min of reperfusion on the modified Langendorff apparatus. Fifty-two isolated hearts of 3-4 week-old immature rabbits were divided into 4 groups randomly. During ischemia, 3 different cardioplegic solutions were administered intermittently by infusion every 15 min (20-25 ml each time in all groups). Group 1: control group (n = 13); group 2: Krebs-Henseleit (K-H) solution with potassium (16 mmol/L) (n = 13); group 3: K-H solution with potassium (16 mmol/L) and pinacidil (50 mumol/L) (n = 13); group 4: K-H solution with potassium (16 mmol/L), pinacidil (50 mumol/L) and glibenclamide (10 mumol/L) (n = 13). The pre-ischemic and post-ischemic myocardial functions were assessed by the percentage recovery of the left ventricular developed pressure (LVDP); the left ventricular end-diastolic pressure (LVEDP); both the positive peak and negative peaks of the first derivative of the left ventricular pressures (+/- dp/dtmax); coronary flow; the level of creatine kinase (CK), lactic dehydrogenase (LDH) and aspartate transcarbamoylase (AST) in coronary sinus venous effluent; and by myocardial ultrastructural changes.
Results: Before myocardial ischemia, there were no significant differences among the four groups in any of the parameters mentioned above. Post-ischemic recovery of LVDP, LVEDP, +/- dp/dtmax, coronary flow, the level of CK, LDH and AST, and myocardial ultrastructural changes were better in group 3 than those in the three other groups.
Conclusions: As a new and effective composition, pinacidil can significantly improve myocardial protection from cardioplegia for immature rabbit hearts.