Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury

Ischemic preconditioning (IP) reduces infarct size in young animals; howeve r, its impact on aging is underinvestigated. The effect of variations in IP stimuli was studied in young, middle-aged, and aged rat hearts. Isolated h earts underwent 35 min of regional ischemia and 120 min of reperfusion. Hea rts with IP were subjected to either one ischemia-reperfusion cycle (5 min of ischemia and 5 min of reperfusion per cycle) or three successive cycles before 35 min of regional ischemia. Additional studies investigated the eff ects of pharmacological preconditioning in aged hearts using the adenosine A, receptor agonist 2-chloro-N-6-cyclopentyladenosine, the protein kinase C analog 1,2-dioctanoyl-sn-glycerol, and the mitochondrial ATP-sensitive pot assium (K-ATP)-channel opener diazoxide. Infarct sizes indicated that the a ged rat heart could not be preconditioned via ischemic or pharmacological m eans. The middle-aged rat heart had a blunted IP response compared with the young adult (only an increased IP stimulus caused a significant reduction in infarct size). These results suggest that there are defects within the I P signaling cascade of the aged heart. Clinical relevance is important if w e are to use any IP-like mimetics to the benefit of an aging population.