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INNOVATIVE METHODOLOGY

Ischemic preconditioning of the whole heart confers protection on subsequently isolated ventricular myocytes

Department of Cardiovascular Sciences, University of Leicester, Glenfield General Hospital, Leicester, United Kingdom

Submitted 24 August 2007 ; accepted in final form 24 October 2007

Current cellular models of ischemic preconditioning (IPC) rely on inducing preconditioning in vitro and may not accurately represent complex pathways triggered by IPC in the intact heart. Here, we show that it is possible to precondition the intact heart and to subsequently isolate individual ventricular myocytes that retain the protection triggered by IPC. Myocytes isolated from Langendorff-perfused hearts preconditioned with three cycles of ischemia-reperfusion were exposed to metabolic inhibition and reenergization. Injury was assessed from induction of hypercontracture and loss of Ca²⁺ homeostasis and contractile function. IPC induced an immediate window of protection in isolated myocytes, with 64.3 ± 7.6% of IPC myocytes recovering Ca²⁺ homeostasis compared with 16.9 ± 2.4% of control myocytes (P < 0.01). Similarly, 64.1 ± 5.9% of IPC myocytes recovered contractile function compared with 15.3 ± 2.2% of control myocytes (P < 0.01). Protection was prevented by the presence of 0.5 mM 5-hydroxydecanoate during the preconditioning stimulus. This early protection disappeared after 6 h, but a second window of protection developed 24 h after preconditioning, with 54.9 ± 4.7% of preconditioned myocytes recovering Ca²⁺ homeostasis compared with 12.6 ± 2.9% of control myocytes (P < 0.01). These data show that "true" IPC of the heart confers both windows of protection in the isolated myocytes, with a similar temporal relationship to in vivo preconditioning of the whole heart. The model should allow future studies in isolated cells of the protective mechanisms induced by true ischemia.

calcium regulation; hypercontracture; metabolic inhibition

This article has been cited by other articles:

				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]