After four hours of cold ischemia and cardioplegic protocol, the heart can still be rescued with postconditioning.
ABSTRACT There is evidence that ischemia lasting more than 4 hours affects cardiac allograft survival. Ischemia and reperfusion are associated with additional deleterious effects. Protective effects of preconditioning are already being used but protocols based on postconditioning have not been evaluated. We tested the impact of postconditioning on hearts maintained in the cold for a long period of total global ischemia and we compared the results with those obtained with pyruvate, a cardioprotective molecule.
Isolated working rat hearts were subjected to a global total ischemia (4 h/4 degrees C), followed by 45 min of reperfusion. Postconditioning consisted of brief total global ischemia applied three times during the onset of reperfusion (ischemia: 30 sec, reperfusion: 30 sec). Superoxide anion production and collagen content were evaluated on cryosections.
Our results showed that postconditioning led to improvements in cardiac functions that were comparable to those conferred by pyruvate. Postconditioning reduced myocardial damage, gave better functional recovery, and better preserved the collagen content. It reduced the duration of arrhythmias at the onset of reperfusion. In the postconditioning group, this improvement was associated with a reduction in superoxide production.
In conclusion, our study showed that postconditioning induced good cardioprotective effects in a long cold (4 hr/4 degrees C) ischemia protocol and led to lower O2 production in part mediated by the reduction in NAPDH oxidase activity. It is interesting to note that, in our experimental conditions, the beneficial effects of postconditioning were comparable to those produced by pyruvate.
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ABSTRACT: Coronary heart disease (CHD) is the leading cause of death worldwide. Coronary artery bypass graft (CABG) surgery remains the procedure of choice for coronary artery revascularisation in a large number of patients with severe CHD. However, the profile of patients undergoing CABG surgery is changing with increasingly higher-risk patients being operated upon, resulting in significant morbidity and mortality in this patient group. Myocardial injury sustained during cardiac surgery, most of which can be attributed to acute myocardial ischaemia–reperfusion injury, is associated with worse short-term and long-term clinical outcomes. Clearly, new treatment strategies are required to protect the heart during cardiac surgery in terms of reducing myocardial injury and preserving left ventricular systolic function, such that clinical outcomes can be improved. ‘Conditioning’ the heart to harness its endogenous cardioprotective capabilities using either brief ischaemia or pharmacological agents, provides a potentially novel approach to myocardial protection during cardiac surgery, and is the subject of this review article.European Journal of Cardio-Thoracic Surgery.
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ABSTRACT: Brief periods of ventricular pacing during the early reperfusion phase (pacing-induced postconditioning, PPC) have been shown to reduce infarct size as measured after 2 h of reperfusion. In this study, we investigated (1) whether PPC leads to maintained reduction in infarct size, (2) whether abnormal mechanical load due to asynchronous activation is the trigger for PPC and (3) the signaling pathways that are involved in PPC. Rabbit hearts were subjected to 30 min of coronary occlusion in vivo, followed by 6 weeks of reperfusion. PPC consisted of ten 30-s intervals of left ventricular (LV) pacing, starting at reperfusion. PPC reduced infarct size (TTC staining) normalized to area at risk, from 49.0 +/- 3.3% in control to 22.9 +/- 5.7% in PPC rabbits. In isolated ejecting rabbit hearts, replacing LV pacing by biventricular pacing abolished the protective effect of PPC, whereas ten 30-s periods of high preload provided a protective effect similar to PPC. The protective effect of PPC was neither affected by the adenosine receptor blocker 8-SPT nor by the angiotensin II receptor blocker candesartan, but was abrogated by the cytoskeletal microtubule-disrupting agent colchicine. Blockers of the mitochondrial K(ATP) channel (5HD), PKC (chelerythrine) and PI3-kinase (wortmannin) all abrogated the protection provided by PPC. In the in situ pig heart, PPC reduced infarct size from 35 +/- 4 to 16 +/- 12%, a protection which was abolished by the stretch-activated channel blocker gadolinium. No infarct size reduction was achieved if PPC application was delayed by 5 min or if only five pacing cycles were used. The present study indicates that (1) PPC permanently reduces myocardial injury, (2) abnormal mechanical loading is a more likely trigger for PPC than electrical stimulation or G-coupled receptor stimulation and (3) PPC may share downstream pathways with other modes of cardioprotection.Archiv für Kreislaufforschung 03/2010; 105(4):523-33. · 7.35 Impact Factor