Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts.
The impact of ischemic preconditioning (IPC) on contraction, Ca(2+) homeostasis, and cell survival was compared in isolated ventricular myocytes from young adult ( approximately 3 mo) and aged ( approximately 24 mo) male Fischer-344 rats. Myocytes were field stimulated at 4 Hz (37 degrees C). Contraction (edge detector) and intracellular Ca(2+) (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(2+) transient amplitudes in reperfusion in young adult and aged cells. IPC did not affect the modest rise in diastolic Ca(2+) in ischemia in young adult myocytes. However, IPC abolished the marked rise in diastolic Ca(2+) 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(2+) transient amplitudes in ventricular myocytes from young adult and aged rats. IPC reduced diastolic Ca(2+) 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.
Dept. of Pharmacology, Dalhousie Univ., 5850 College St., Sir Charles Tupper Medical Bldg., Halifax, NS, Canada B3H 1X5.
J Darcy
JD
O'Brien
Susan E
SE
Howlett
D000367:Age Factors; D000818:Animals; D020013:Calcium Signaling; D048429:Cell Size; D002470:Cell Survival; D004558:Electric Stimulation; D006352:Heart Ventricles / Q000378:metabolism; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D023421:Models, Animal; D009119:Muscle Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors