Ischemic postconditioning of the isolated human myocardium: Role of the applied protocol

Abstract

BackgroundIschemic postconditioning (IPostC), has been proposed as a useful approach to reduce infarct size in all species, but its clinical utility remains unclear.ObjectiveTo investigate the role played by the protocol used on the efficacy of IPostC in protecting the diseased human myocardium.MethodsMyocardial atrial samples from patients were subjected to a 90 min ischemia/120 min reoxygenation followed by different IPostC protocols to investigate the role of the time of ischemia (30, 60, 90 and 120 s) and the number of cycles (1, 2, 3 and 4) with 60 and 120 s of total ischemic time. Muscles were also subjected to ischemic preconditioning (IPreC). The release of lactate dehydrogenase (LDH) and the measurement of tetrazolium bromide (MTT) were determined.ResultsIPostC increased the LDH and decreased the MTT values from those of control, independently of the duration of the conditioning ischemia. LDH and MTT values also worsened by augmenting the number of IPostC cycles whereas they were significantly improved by IPreC. However, analysis of individual results indicated that in approximately 1/3 of the cases IPostC exhibited some degree of protection especially in the presence of increased ischemic injury.ConclusionsThe present findings show that IPostC of the human myocardium may be influenced by the protocol used and also by the degree of the preceding ischemic injury. IPostC was beneficial in approximately 1/3 of the cases; however in the remaining cases it increased ischemic damage and, therefore, these results raise a word of caution on its broad clinical use.

Duration of the Reoxygenation Interval Applied before Ischemic Post-conditioning: Fine-Tuning the Protocol for Human Myocardium

“…Our study is the first to demonstrate that the human myocardium is better protected by an IPostC protocol with a 120 or 180 s reoxygenation interval than when an interval of 30 or 60 s is used. It also confirms our previous finding [16] that despite this only approximately one-third of the human myocardium samples obtained from patients undergoing cardiac surgery can be protected by the best IPostC protocol.…”

“…One subset of muscles was subjected to ischemia/ reperfusion (I/R) alone. The other muscles were subjected to a single cycle of IPostC in which the duration of ischemia was fixed at 120 s, a time previously shown to be the most effective IPostC protocol in our laboratory [16], and preceded by different reoxygenation intervals: 30, 60, 120, or 180 s. Samples not subjected to ischemia and perfused aerobically during the entire experimental period served as aerobic controls (AC). …”

“…One reason for these variable results may be the use of different IPostC protocols. Using an in vitro model of ischemia/reoxygenation of human myocardium, our laboratory reported that the most effective IPostC protocol was one 120 s cycle of reperfusion/ischemia after 90 min of normothermic global ischemia [16]. However, the optimal time of the interval between the termination of prolonged ischemia and the application of the short ischemia of the IPostC protocol, a time when reperfusion injury is most likely, remains unclear.…”

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study

“…Based on the above observations, the aim of the present study was to determine the "vascular conditioning" potential of RIC by investigating its effects on endothelial glycocalyx, arterial stiffness, and oxidative stress burden after primary PCI, as well as to identify the role of specific miRs , NOx and IL-6 production on vascular function early post MI. With regards to the implemented protocols, there is evidence supporting that a total ischemic period of 5 to 10 minutes may confer the optimum ischemic conditioning stimulus [3,35], while 5 minutes of ischemic inflation induce maximal shear-mediated NO release and vasodilation in FMD studies [14].…”

Postconditioning with Nitrates Protects Against Myocardial Reperfusion Injury: A New Use for an Old Pharmacological Agent

“…Ischemic preconditioning (IPC) provides the strongest endogenous protection against cell death after transient coronary occlusion and against cell injury from reperfusion [33,34]. Clinical evidence suggests that this phenomenon may be greatly protective by attenuation of lethal reperfusion injury [35,36] and reduced release of biomarker in the surgical settings [37,38].…”