PRECONDITIONING DOES NOT PREVENT POSTISCHEMIC DYSFUNCTION IN AGING HEART

Objectives. This study was performed to investigate the effect of sing le or multiple brief periods of ischemia and the administration of exo genous norepinephrine before a more prolonged ischemic period and afte r reperfusion in adult and senescent isolated and perfused rat hearts. Background. The mortality rate for coronary artery disease is greater in the elderly. Ischemic preconditioning has been proposed as an endo genous form of protection against ischemia-reperfusion injury. However , the role of preconditioning in aging heart is unknown. Methods. We c ompared the protective effect of preconditioning transient ischemic an d norepinephrine stimuli against 20 min of global normothermic ischemi a and 40 min of reperfusion in isolated perfused hearts of adult (6 mo nths old) and senescent (24 months old) rats. Norepinephrine release i n coronary effluent was determined by high performance liquid chromato graphy. Results. Final recovery of percent developed pressure was impr oved after single preconditioning transient ischemic and norepinephrin e stimuli in adult hearts (87.7 +/- 9% and 82.3 +/- 8.7%) versus uncon ditioned control hearts (50.6 +/- 4.8%, p < 0.01 [mean +/- SD]). The e ffect of preconditioning on developed pressure recovery was not presen t in senescent hearts after transient ischemic stimulus (39.8 +/- 4.9% vs. 41.6 +/- 5.8%, p = NS) but was present after norepinephrine stimu lus (74.3 +/- 10.5, p < 0.01), Norepinephrine release significantly in creased after preconditioning transient ischemic stimulus in adult but not in senescent hearts (p < 0.01 vs. adult), Transient ischemic- and norepinephrine-induced preconditioning was blocked by alpha-adrenergi c receptor antagonists in both adult and senescent hearts. Multiple tr ansient ischemic stimuli were able to reduce postischemic dysfunction in adult but not in senescent hearts. Conclusions. Preconditioning tra nsient ischemic stimulus significantly reduces postischemic dysfunctio n in adult but not in senescent hearts, whereas exogenous norepinephri ne is able to mimic preconditioning in both adult and senescent hearts . Ischemic preconditioning induces an increase in norepinephrine relea se in adult but not in senescent hearts. Preconditioning induced by tr ansient ischemic stimulus and norepinephrine was abolished by alpha-ad renergic receptor blockade in both adult and senescent hearts. Thus, o ur data demonstrate that preconditioning is absent in aging heart and is probably related to the reduction of norepinephrine release and alp ha-adrenergic receptor stimulation in response to ischemic preconditio ning.