The myocardium has an innate ability to protect itself from ischemic events. This protection occurs when the myocardium is exposed to a brief ischemic period prior to a more extreme ischemic event. This is termed ischemic preconditioning. Ischemic preconditioning induces a series of molecular pathways that protect the cardiac myocyte; first, for a period of 1-6 hours (early preconditioning) and, also, for a second period from 24-72 hours (delayed phase). The early preconditioning is mediated by the release of adenosine which induces a protective signal that is related to the mitochondrial KATP channel activation and activation of the δ-opioid and bradykinin receptors. The delayed phase is related to the induction of inducible nitric oxide synthase, superoxide dismutase and heat-shock proteins. Indirect evidence indicates that O2-derived free radicals are involved in the delayed phase, as noted in the early preconditioning phase. Applying ischemic preconditioning to clinical practice can be dangerous and difficult to implement in a controlled fashion. However, recent studies have shown that the use of volatile anesthetics, such as sevoflurane, isoflurane and desflurane, can mimic the early phase of ischemic preconditioning through a multi-pathway signaling of mitochondrial KATP channels. This important finding can easily be applied to clinical practice for patients undergoing surgery. It can also be significantly important for patients undergoing off-pump cardiac bypass surgery or cardiac bypass surgery where there is no cross-clamp or cardioplegia used where the probability of myocardial ischemia is greatly increased. This report will, therefore, discuss the mechanism, safety and efficacy of volatile anesthetics as inducers of cardiac preconditioning.

PurposeDodecafluoropentane emulsion (DDFPe) is a perfluorocarbon with high oxygen dissolving, transport, and delivery capacity that may offer the potential to limit ischemic injury prior to clinical reperfusion. Here we investigated the cardiac protective potential of DDFPe in a mouse model of myocardial infarction.MethodsMyocardial infarction was initiated by permanent ligation of the left anterior descending (LAD) coronary artery. Mice were administered vehicle or 5-hydroxydecanoate (5-HD) intravenously 10 min before LAD occlusion followed by a single intravenous administration of vehicle or DDFPe immediately after occlusion. Heart tissue and serum samples were collected 24 after LAD occlusion for measurement of infarct size and cardiac troponin I (cTnI) levels, respectively.ResultsDDFPe treatment reduced infarct size by approximately 72 % (36.9 ± 4.2 % for vehicle vs 10.4 ± 2.3 % for DDFPe; p < 0.01; n = 6–8) at 24 h. Serum cTnI levels were similarly reduced by DDFPe (35.0 ± 4.6 ng/ml for vehicle vs 15.8 ± 1.6 ng/ml for DDFPe; p < 0.01; n = 6–8). Pretreatment with 5-HD, a mitochondrial ATP-sensitive potassium channel (mitoKATP) inhibitor, blocked the reduction in infarct size (29.2 ± 4.4 % for 5-HD vs 35.4 ± 7.4 % for 5-HD+DDFPe; p = 0.48; n = 6–8) and serum cTnI levels (27.4 ± 5.1 ng/ml for 5-HD vs 34.6 ± 5.3 ng/ml for 5-HD+DDFPe; p = 0.86; n = 6–8) by DDFPe.ConclusionOur data indicate a cardiac protective role of DDFPe that persists beyond its retention time in the body and is dependent on mitoKATP, an important mediator of ischemic preconditioning induced cardiac protection.

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