Ischemic preconditioning in isolated cells.

Abstract

Ischemic preconditioning describes the increased resistance to myocardial infarction that follows short sublethal periods of ischemia. After the ischemia that triggers preconditioning, there are 2 phases of protection: an early (short-lived) phase termed early or classic preconditioning1 and a late (more prolonged) phase termed late preconditioning or the second window of protection.2 The purpose of the present minireview is to highlight the contributions being made to our current understanding of early preconditioning by models based on isolated cardiac cells. Within the preconditioning literature are disparate findings usually explained by variations in species, maturity, preconditioning trigger, anesthetic, and/or choice of end point. This lack of generality is a particular problem with cell-based models. Variability in the circumstances of the trigger, simulation of ischemia, in vitro maintenance conditions, cell type, and species of origin result in innumerable combinations and permutations (see online data supplement at http://www.circresaha.org), making findings difficult enough to compare between cell models let alone between these models and preconditioning in the whole heart. Given these drawbacks, why are an increasing number of preconditioning investigators adopting a cell-based approach? Little controversy surrounds the surface receptors able to trigger preconditioning. In the whole heart, their successful pharmacological manipulation can be verified by alterations in vascular resistance, rate and strength of contraction, and atrioventricular conduction. However, attention has now shifted to intracellular signaling pathways, and the specificity of pharmacological agents is diminished, their effects on physiology are less certain, and their costs are greatly increased. The cell-based models overcome these disadvantages through a small volume of distribution, through an ability to manipulate signaling proteins by the introduction of cDNAs, antisense RNA, recombinant protein, and interfering peptides, and through the interrogation of altered signaling cascades and their consequences within a homogeneous cell type. However, these advantages are at the expense of …