Abstract 1287: Implication of Mitochondrial ATP-Sensitive Potassium Channel During Ischemic Postconditioning in Pigs
Objective: To test whether ischemic postconditioning (postcon) is cardioprotective in pigs and involves mitochondrial ATP-sensitive potassium channel (mito-KATP).
Methods: In barbital-anesthetized open-chest pigs, left anterior descending coronary artery (LAD) was occluded for 30 min and reperfused for 3 hours. 6 groups were studied (N = 7 in each). In the control group, there was no additional intervention. Preconditioning (Precon) was elicited by 2 cycles of 5 min ischemia followed by 5 min reperfusion. Postcon was achieved by 3 cycles of 1 min reperfusion and 1 min reocclusion before the 3 h reperfusion. Involvement of mito-KATP was assessed by injection of 10 mg/kg of 5 hydroxydecanoate (5-HD) in the left atrium 7 min before postcon and reperfusion (Postcon + 5-HD), before reperfusion without postcon (IR + 5-HD) or by injection of 2 mg/kg Diazoxide in the left atrium before reperfusion without postcon (IR+Dia). Mitochondrial function was studied at the end of the protocols on permeabilized skinned fibers prepared from tissue harvested in the area at risk (AAR) and the control non ischemic zone. Infarct size (IS) was measured after TTC staining.
Results: IS/AAR ratio was significantly decreased in the Precon (10 ± 2%) and Postcon (4 ± 3%) compared to control (40 ± 5%, p < 0.05). Postcon completely prevented the occurrence of reperfusion arrhythmias. 5-HD abolished the protective effect of postconditioning (IS/AAR = 34 ± 4%, p < 0.05 vs Control) and was associated with occurrence of reperfusion arrhythmias. Diazoxide injected before reperfusion without postcon did not afford any protective effect and injection of 5-HD before reperfusion with out postcon gave similar infarct size as in the IR group. Analysis of mitochondrial function showed similar significant decrease in maximal respiration rates and in the affinity of mitochondrial respiration for ADP in the AAR of control and postcon + 5-HD groups but not after pre or postconditioning.
Conclusion: Ischemic postconditioning reduces infarct size in pigs to a similar extent as preconditioning, abolishes reperfusion arrhythmias. Opening of mito-KATP is required but not sufficient to obtain the cardioprotection.