Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode.

Abstract

We have shown previously that preconditioning myocardium with four 5-minute episodes of ischemia and reperfusion dramatically limited the size of infarcts caused by a subsequent 40-minute episode of sustained ischemia. The current study was undertaken to assess whether the same preconditioning protocol slowed the loss of high energy phosphates, limited catabolite accumulation, and/or delayed ultrastructural damage during a sustained ischemic episode. Myocardial metabolites and ultrastructure in the severely ischemic subendocardial regions were compared between control and preconditioned canine hearts. Hearts (four to 10 per group) were excised after 0, 5, 10, 20, or In an attempt to separate the effects of catabolite accumulation from those of ATP depletion, we have examined the effects of repeated coronary occlusions. We hypothesized that repeated coronary occlusions might cause partial depletion of ATP, whereas intermittent reperfusion would wash out ischemic catabolites. In a recent study,' we proposed that multiple brief ischemic episodes actually might protect the heart from a subsequent sustained ischemic insult. To test this hypothesis, dogs were "preconditioned" with four 5-minute episodes of ischemia, each separated by 5 minutes of reperfusion, and then subjected immediately to a sustained occlusion of either 40 minutes or 3 hours. Control animals received either a single 40-minute or 3-hour occlusion. In the 40-minute study, infarcts in preconditioned hearts were smaller than controls at any level of collateral flow, averaging 25% of control infarct size. In the 3-hour study, preconditioning had no effect on infarct size.by guest on May 12, 2018

Migration of Resident Cardiac Stem Cells in Myocardial Infarction

“…Instead such preconditioning protects the heart from subsequent ischemic injury (Murry et al, 1990). Recently, Gyongyosi et al (2010) have shown that HPC enhances migration and recruitment of hematopoietic stem cells (HSC) and mesenchymal stem cells (MSC) to infarcted myocardium in a porcine myocardial ischemiareperfusion model.…”

Medical and Cellular Implications of Stunning, Hibernation, and Preconditioning

“…[171][172][173][174] A signature of preconditioned myocardium in the canine model is slowed ATP depletion and lactate accumulation during the sustained episode of ischemia. 175 This characteristic of slowed energy utilization by preconditioned tissue may be related to the mechanism whereby ischemic preconditioning delays cell death. Murry et al 175 pointed out that preconditioned tissue also exhibits a high creatine phosphate concentration, more intracellular glucose, less glycogen, and a smaller adenine nucleotide pool, contains more Kϩ, and is somewhat edematous.…”

Adenosine. The signal of life?

“…Preconditioning refers to the observation that brief periods of myocardial ischemia provide protection against subsequent ischemia/reperfusion injury. 27 The effect of preconditioning can be mimicked by adenosine agonists. Preconditioning is abolished in the presence of adenosine receptor antagonists.28 Thus, the augmented adenosine release in the presence of the three antioxidants could have a conditioning effect on neighboring microvascular regions not yet ischemic.…”