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1Department of Pharmacology and 2Division of Geriatric Medicine, Dalhousie University, Halifax, Nova Scotia, Canada
Submitted 16 January 2008 ; accepted in final form 3 March 2008
This study examined the impact of age on contractile function, Ca2+ 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°C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca2+ 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. Ca2+ 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 Ca2+ 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 Ca2+ 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.
calcium transients; cell shortening; senescence
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J. D. O'Brien and S. E. Howlett Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H768 - H777. [Abstract] [Full Text] [PDF] |
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