Postconditioning: a mechanical maneuver that triggers biological and molecular cardioprotective responses to reperfusion

Abstract

Infarct size is determined not only by the duration and severity of ischemia, but also by pathological processes initiated at reperfusion (reperfusion injury). Numerous pharmacological strategies have been reported which administer drugs at or just before the onset of reperfusion, with subsequent salubrious effects, notably a reduction in infarct size. However, few if any of these strategies have become standard of care in the catheterization laboratory setting. Postconditioning, defined as repeated brief cycles of reperfusion interrupted by ischemia (or hypoxia) applied at the onset of reperfusion, was recently introduced as a mechanical strategy to attenuate reperfusion injury. Postconditioning intervenes only during the first few minutes of reperfusion. However, it reduces endothelial activation and dysfunction, the inflammatory response to reperfusion, necrosis, and apoptosis both acutely and long-term. Cardioprotection has been demonstrated by multiple independent laboratories and in multiple species. Postconditioning stimulates G-protein coupled receptors by their cognate endogenously released ligands and surprisingly activates survival kinases that may converge on mitochondrial K(ATP) channels and the permeability transition pore. Postconditioning has been shown in two clinical studies to reduce infarct size in patients undergoing percutaneous coronary intervention in the catheterization laboratory, and at least five other studies are in some phase of implementation. This significant reduction in infarct size has implications for reduction in heart failure as a consequence of myocardial infarction, but this link has yet to be demonstrated. The salubrious effects of postconditioning are an indirect validation of the experimental and clinical importance of reperfusion injury in the setting of coronary artery occlusion.

Cardioprotection Techniques: Preconditioning, Postconditioning and Remote Con-ditioning (Basic Science)

“…Once the cardioprotective signal has been conveyed from the remotely preconditioned organ to the heart, intracellular signal transduction mechanisms are recruited within cardiomyocytes which are similar to those that participate in IPC and IPost [191]. These include the ligand binding to G-protein cell surface coupled receptors such as adenosine [170], bradykinin [171], opioids [172], angiotensin [192], and endocannabinoids [174].…”

Postconditioning against ischaemia-reperfusion injury: ready for wide application in patients?

“…Similar to IPC, the IPOC stimulus also appears to result in the activation of specifically G protein-coupled receptors (GPCRs) by endogenous ligands, such as adenosine, opioids, and bradykinin, providing the initial trigger for recruitment of survival signalling pathways. 8 The adenosine receptor was the first GPCR to be linked with IPOC. Thus, the reduction in myocardial infarct size elicited by IPOC was abolished in the presence of 8-p-(sulphophenyl) theophylline, a non-specific adenosine receptor blocker.…”

Targeting the Endothelium

“…The outcomes from postconditioning strategies depend upon the intervention used. (35)(36)(37)(38)(39)(40)(41) Following the successful outcome of CPR, delayed postconditioning has the potential for clinical application. (27,28) The Endothelium during Cardiac Arrest and Resuscitation Evidence that the endothelium plays an important role during and after cardiac arrest comes from both animal models and clinical studies.…”