No abstract

This study examined the impact of age on contractile function, Ca(2+) homeostasis, and cell viability in isolated myocytes exposed to simulated ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field-stimulated at 4 Hz (37 degrees C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca(2+) were measured simultaneously with an edge detector and fura-2. Cell viability was assessed by Trypan blue exclusion. Ischemia (20-45 min) depressed amplitudes of contraction equally in isolated myocytes from young adult and aged animals. The degree of postischemic contractile depression (stunning) was comparable in both groups. Ca(2+) transient amplitudes were depressed in early reperfusion in young adult and aged cells and then recovered to preischemic levels in both groups. Cell viability also declined equally in reperfusion in both groups. In short, some cellular responses to simulated ischemia and reperfusion were similar in both groups. Even so, aged myocytes exhibited a much greater and more prolonged accumulation of diastolic Ca(2+) in ischemia and in early reperfusion compared with myocytes from younger animals. In addition, the degree of mechanical alternans in ischemia increased significantly with age. The observation that there is an age-related increase in accumulation of diastolic Ca(2+) in ischemia and early reperfusion may account for the increased sensitivity to ischemia and reperfusion injury in the aging heart. The occurrence of mechanical alternans in ischemia may contribute to contractile dysfunction in ischemia in the aging heart.

O'Brien JD, Howlett SE. Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts. Am J Physiol Heart Circ Physiol 295: H768 -H777, 2008; doi:10.1152/ajpheart.00432.2008.-The impact of ischemic preconditioning (IPC) on contraction, Ca 2ϩ homeostasis, and cell survival was compared in isolated ventricular myocytes from young adult (ϳ3 mo) and aged (ϳ24 mo) male Fischer-344 rats. Myocytes were field stimulated at 4 Hz (37°C). Contraction (edge detector) and intracellular Ca 2ϩ (fura-2) were measured simultaneously. Viability was assessed with trypan blue. All cells were exposed to 30 min of simulated ischemia followed by reperfusion. Some cells were preconditioned by exposure to 5 min of simulated ischemia before prolonged ischemia. Pretreatment with IPC abolished postischemic contractile depression, inhibited diastolic contracture, and increased Ca 2ϩ transient amplitudes in reperfusion in young adult and aged cells. IPC did not affect the modest rise in diastolic Ca 2ϩ in ischemia in young adult myocytes. However, IPC abolished the marked rise in diastolic Ca 2ϩ observed in ischemia and early reperfusion in aged myocytes. IPC also suppressed mechanical alternans in ischemia in aged cells, but younger myocytes showed little evidence of mechanical alternans whether or not cells were preconditioned. IPC markedly improved cell viability in reperfusion in young adult but not aged cells. These results suggest that IPC augments the recovery of contractile function in reperfusion by increasing Ca 2ϩ transient amplitudes in ventricular myocytes from young adult and aged rats. IPC reduced diastolic Ca 2ϩ accumulation in ischemia in aged myocytes, which may diminish the severity of mechanical alternans in aged cells. Nonetheless, the efficacy of IPC is compromised in aging, as IPC did not improve survival of aged myocytes exposed to ischemia and reperfusion. cardioprotection; reperfusion; mechanical alternans; senescence IT IS WELL ESTABLISHED that aged hearts are more sensitive to ischemia and reperfusion injury than younger adult hearts (14,22,27). Studies in humans have shown that morbidity and mortality rates after acute myocardial infarction are much higher in older adults than in younger patients (37,50,54). Also, the risk of death following procedures that cause reperfusion increases with age (9, 53). Similar results have been reported in animal models of aging. Studies of ischemia and reperfusion injury in Langendorff-perfused hearts have shown that infarct size is greater in hearts from aged animals than in younger hearts, while recovery of contractile function in reperfusion declines with age (3,16,19,31,39,48,55). Many of these detrimental effects of myocardial ischemia and reperfusion are thought to be linked to a rise in intracellular free Ca 2ϩ levels in cardiac myocytes (30,40). Indeed, individual ventricular myocytes isolated from aged rats accumulate more diastolic Ca 2ϩ in ischemia and early reperfusion than cells from younger hearts (43)....

No abstract