Effects of ischemia and reperfusion on isolated ventricular myocytes from young adult and aged Fischer 344 rat hearts

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.

Efficacy of selective NCX inhibition by ORM-10103 during simulated ischemia/reperfusion

“…The latter also facilitates Ca 2 þ influx, considerably increasing the amount of [Ca 2 þ ] i to be extruded (Bers, 2008;Lee and Allen, 1992 (O'Brien et al, 2008). In contrast, RT 50 was shortened.…”

Chronic Tempol treatment restores pharmacological preconditioning in the senescent rat heart

“…Ventricular myocytes were obtained by enzymatic dissociation as previously described (43,61). Briefly, rats were injected intraperitoneally with heparin (3,000 U/kg) to inhibit blood coagulation.…”

Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts

“…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). These findings indicate that aging hearts are more sensitive to ischemia and reperfusion injury than younger hearts and suggest that alterations at the level of the cardiac myocyte may increase the susceptibility to ischemia and reperfusion injury with age.…”

“…The present study used a cellular model of simulated ischemia and reperfusion developed in this laboratory and recently adapted for use in rat myocytes (43). Here, we evaluated and compared differences in contractile function, intracellular Ca 2ϩ homeostasis, and cell viability throughout ischemia and reperfusion in ventricular myocytes isolated from the hearts of young adult (ϳ3 mo) and aged (ϳ24 mo) male Fischer-344 rats in the absence and presence of IPC.…”