ROLE OF CELLULAR ENERGETICS IN ISCHEMIA-REPERFUSION AND ISCHEMIC PRECONDITIONING OF MYOCARDIUM

A short period of ischemia followed by reperfusion produces a state of affairs in which the cells' potential for surviving longer ischemia i s enhanced. This is called ischemic preconditioning. The effects of pr econditioning are also related to the reperfusion damage which ensues upon tissue oxygenation. The role of the cellular energy state in repe rfusion damage remains an enigma, although ischemic preconditioning is known to trigger mechanisms which contribute to the prevention of unn ecessary ATP waste. In some species up to 80% of ATP hydrolysis in isc hemia can be attributed to mitochondrial F-1-F-O-ATPase (ATP synthase) , and a role for its inhibitor protein (IF1) in ATP preservation has b een proposed. Although originally regarded as limited to large animals with a slow heart beat, inhibition by IF1 is probably a universal phe nomenon. Coincidentally with ATPase inhibition, the decline in cellula r ATP slows down, but even so the difference in ATP concentration betw een preconditioned and non-conditioned hearts is still small at the fi nal stages of a long ischemia, when the beneficial effect of precondit ioning is observable, although the energy state during reperfusion rem ains low in hearts which do not recover.