Cardioprotection 'Outside the Box' - The evolving paradigm of remote preconditioning
ABSTRACT Conventional ischemic preconditioning is the phenomenon whereby brief episodes of myocardial ischemia render the ischemic territory resistant to a subsequent, sustained ischemic insult. A growing body of evidence further indicates that brief ischemia applied in distant organs and tissues can also protect naïve, virgin myocardium from ischemic injury. In this review, we describe the initial observations that provided the impetus for the study of 'remote preconditioning', and summarize our current knowledge of the three facets of 'preconditioning at a distance' --intra-cardiac, inter-organ and transferred inter-cardiac preconditioning.
- SourceAvailable from: Sebastiaan T Roos
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- "The first evidence that repetitive induction of ischemia and reperfusion in a remote region can provide cardioprotection was delivered in 1993 by Przyklenk et al. . A conditioning protocol in the circumflex coronary artery reduced infarct size in a myocardial infarction induced by LAD occlusion. "
ABSTRACT: Reperfusion by means of percutaneous coronary intervention or thrombolytic therapy is the most effective treatment for acute myocardial infarction, markedly reducing mortality and morbidity. Reperfusion however induces necrotic and apoptotic damages to cardiomyocytes, that were viable prior to reperfusion, a process called lethal reperfusion injury. This process, consisting of many single processes, may be responsible of up to half of the final infarct size. A myriad of therapies as an adjunct to reperfusion have been studied with the purpose to attenuate reperfusion injury. The majority of these studies have been disappointing or contradicting, but recent proof-of-concept trials show that reperfusion injury still is a legitimate target. This overview will discuss these trials, the progression in attenuating myocardial reperfusion injury, promising therapies, and future perspectives.International journal of cardiology 11/2013; 170(3). DOI:10.1016/j.ijcard.2013.11.007 · 6.18 Impact Factor
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- "Nevertheless, remote preconditioning has different protective mechanisms from conventional preconditioning. For example, conventional preconditioning adapts the ischemic organ locally to a subsequent severe ischemia, but remote preconditioning conducted in a non-vital organ affects the heart through humoral factors or via nervous connections (Przyklenk et al., 2003). Similarly, remote preconditioning may protect against brain ischemia through different mechanisms compared with conventional preconditioning; thus, they may have different therapeutic time windows. "
ABSTRACT: Remote ischemic preconditioning is an emerging concept for stroke treatment, but its protection against focal stroke has not been established. We tested whether remote preconditioning, performed in the ipsilateral hind limb, protects against focal stroke and explored its protective parameters. Stroke was generated by a permanent occlusion of the left distal middle cerebral artery (MCA) combined with a 30 min occlusion of the bilateral common carotid arteries (CCA) in male rats. Limb preconditioning was generated by 5 or 15 min occlusion followed with the same period of reperfusion of the left hind femoral artery, and repeated for two or three cycles. Infarct was measured 2 days later. The results showed that rapid preconditioning with three cycles of 15 min performed immediately before stroke reduced infarct size from 47.7+/-7.6% of control ischemia to 9.8+/-8.6%; at two cycles of 15 min, infarct was reduced to 24.7+/-7.3%; at two cycles of 5 min, infarct was not reduced. Delayed preconditioning with three cycles of 15 min conducted 2 days before stroke also reduced infarct to 23.0+/-10.9%, but with two cycles of 15 min it offered no protection. The protective effects at these two therapeutic time windows of remote preconditioning are consistent with those of conventional preconditioning, in which the preconditioning ischemia is induced in the brain itself. Unexpectedly, intermediate preconditioning with three cycles of 15 min performed 12 h before stroke also reduced infarct to 24.7+/-4.7%, which contradicts the current dogma for therapeutic time windows for the conventional preconditioning that has no protection at this time point. In conclusion, remote preconditioning performed in one limb protected against ischemic damage after focal cerebral ischemia.Neuroscience 03/2008; 151(4):1099-103. DOI:10.1016/j.neuroscience.2007.11.056 · 3.33 Impact Factor
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ABSTRACT: ABSTRACT We have shown that intermittent interruption of immediate re-flow at reperfusion (i.e., postconditioning) reduces ,infarct size in in vivo models after ischemia. Cardioprotection of postconditioning has been associated with attenuation of neutrophil-related events. However, it is unknown,whether postconditioning before,reoxygenation after hypoxia in cultured cardiomyocytes in the absence ,of neutrophils ,confers protection. This study tested the hypothesis that prevention of cardiomyocyte damage by ,hypoxic ,postconditioning (Post-con) is associated ,with a reduction ,in generation of reactive ,oxygen ,species (ROS) and intracellular Ca, overload. Primary cultured neonatal rat cardiomyocytes were ,exposed ,to 3 h ,hypoxia ,followed ,by 6 ,h of ,reoxygenation. Cardiomyocytes were ,postconditioned after the 3 h ,index hypoxia ,by three ,cycles of 5 min of