Aim: 

Postconditioning was shown to protect human heart against acute reperfusion injury. We showed previously that opening of mitochondrial permeability transition pore (MPTP) is involved in reperfusion-induced hypercontracture and necrosis of cardiac myocytes. The aim of present study was to study whether MPTP opening is involved in postconditioning-protection and whether this is due to a delay in cellular pH recovery.

Methods: 

Isolated rat's cardiac myocytes were subjected to simulated ischemia and reperfusion. Postconditioning, i.e., 3 repetitive cycles of anoxic and 3 of normoxic perfusion, was applied during the first minutes of reperfusion. MPTP opening was monitored by measuring the mitochondrial membrane potential (Dy) with JC-1; cellular pH (pHi) with BCECF; and necrosis with propidium iodide.

Results: 

Simulated ischemia led to mitochondrial depolarization and to a decrease in pHi. During the first two minutes of reperfusion Dy recovered, but collapsed after 5 min of reperfusion indicating MPTP Opening. At this time point, pHi recovered to 35% of initial value and the reperfused cells developed contracture and necrosis. In postconditioned cells, collapse in Dy, contracture, and necrotic cells death were significantly prevented (p<0.05 vs. control). pHi recovery was significantly delayed but reached higher values in postconditioned cells.

Conclusions: 

Postconditioning prevents reperfusion injury by limiting the opening of MPTP during reperfusion due to a delay in cellular pH recovery.