Mitochondrial permeability transition pore (mPTP) opening is a crucial event in cardiomyocyte death after I/R. We questioned whether preconditioning (PC) may inhibit
mPTP opening during
ischemia and/or during reperfusion and whether this effect would persist as reperfusion evolves. Anesthetized New Zealand white rabbits underwent a test
ischemia followed by reperfusion.
Ischemia lasted either 10 or 30 min, whereas reperfusion duration varied from 5 to 20, 60 and up to 240 min. For each duration of
ischemia and reperfusion, animals were randomized as either control or PC. Preconditioning was induced by 5 min of
ischemia followed by 5 min of reperfusion. Mitochondria were isolated from myocardium at risk for assessment of the
calcium retention capacity (CRC) (potentiometric technique) used here as an index of sensitivity of the
mPTP to Ca2+ loading. In controls, the CRC was moderately reduced after
ischemia alone, but reperfusion severely and time-dependently accelerated further CRC reduction. Preconditioning failed to modify
mPTP opening during
ischemia alone, but significantly improved CRC during reperfusion. This protective effect persisted as reperfusion evolved. These data suggest that (a) reperfusion strikingly increases the susceptibility to Ca2+-induced
mPTP opening, and that (b) PC inhibits
mPTP opening at reflow and throughout the first hours of reperfusion.