Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a K_ATP-dependent mechanism: first demonstration of remote ischemic perconditioning

Abstract

RK. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a K ATP-dependent mechanism: first demonstration of remote ischemic perconditioning. Am J Physiol Heart Circ Physiol 292: H1883-H1890, 2007. First published December 15, 2006; doi:10.1152/ajpheart.00617.2006.-Remote ischemic preconditioning reduces myocardial infarction (MI) in animal models. We tested the hypothesis that the systemic protection thus induced is effective when ischemic preconditioning is administered during ischemia (PerC) and before reperfusion and examined the role of the K ϩ -dependent ATP (K ATP) channel. Twenty 20-kg pigs were randomized (10 in each group) to 40 min of left anterior descending coronary artery occlusion with 120 min of reperfusion. PerC consisted of four 5-min cycles of lower limb ischemia by tourniquet during left anterior descending coronary artery occlusion. Left ventricular (LV) function was assessed by a conductance catheter and extent of infarction by tetrazolium staining. The extent of MI was significantly reduced by PerC (60.4 Ϯ 14.3 vs. 38.3 Ϯ 15.4%, P ϭ 0.004) and associated with improved functional indexes. The increase in the time constant of diastolic relaxation was significantly attenuated by PerC compared with control in ischemia and reperfusion (P ϭ 0.01 and 0.04, respectively). At 120 min of reperfusion, preload-recruitable stroke work declined 38 Ϯ 6% and 3 Ϯ 5% in control and PerC, respectively (P ϭ 0.001). The force-frequency relation was significantly depressed at 120 min of reperfusion in both groups, but optimal heart rate was significantly lower in the control group (P ϭ 0.04). There were fewer malignant arrhythmias with PerC during reperfusion (P ϭ 0.02). These protective effects of PerC were abolished by glibenclamide. Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K ATP channeldependent mechanism. Understanding this process may have important therapeutic implications for a range of ischemia-reperfusion syndromes. remote preconditioning; cardioprotection REPERFUSION STRATEGIES are well established for the treatment of evolving clinical ischemia-reperfusion (I/R) syndromes. Recent approaches to further improve outcomes after myocardial infarction (MI) have focused on strategies to protect the myocardium during the ischemic and reperfusion phases, such as sodium-hydrogen pump inhibitors, glucose/insulin infusions, and anti-complement therapy, although these have shown no major additional benefits (15,16,26).One successful approach in the experimental setting is ischemic preconditioning, whereby prior sublethal I/R induces a state of protection against a subsequent prolonged ischemic episode (18). However, ischemic preconditioning has not translated into the clinical setting, not only because it is impossible to predict clinical acute coronary syndromes, but also, even in the setting of predictable I/R injury ...

Efeito protetor do per-condicionamento isquêmico remoto nas lesões da síndrome de isquemia e reperfusão renal em ratos

“…Schmidt et al reported the per-ischemic remote technique (rPerC) 9 , which consists in applying remote ischemia through a tourniquet applied to the hind limb of pigs during the main duration of ischemia, which was actually effective in preventing reperfusion injury in ischemia myocardial. This protective effect was corroborated by further studies involving myocardial ischemia, and the procedure was expanded to cerebral ischemia 10,11 .…”

Perconditioning combined with postconditioning on kidney ischemia and reperfusion

“…Perconditioning is the newest technique described to mitigate IR injury in many tissues 15,18,20 . Our study is the first evaluate of the potential protective effect of PER alone or combined with POS on kidney IR-induced injury, that only be test before in myocardium 15,20 , brain 17,26 , and liver 18 .…”

“…Based on fact that perconditioning is performed in a distant tissue, is a non-invasive procedure and do not increase the surgical time, thus does not require direct access to the artery and could be easily applied during the surgery or endovascular surgery [15][16][17][18][19] ; this ischemic conditioning must be test in human IR syndromes 20,31 . However, new studies aim to understanding the mechanism are need 32 .…”

“…Schmidt et al 15 demonstrated the concept of remote ischemic perconditioning (PER). They applied a tourniquet to a porcine limb to produce alternating periods of occlusion and reperfusion while the myocardium was under ischemia.…”

“…Mechanisms underlying the remote ischemic conditioning are barely understood. It is known that its protective effects are mediated through potassium channels 15 , and through the cellular activation of reperfusion injury salvage kinase pathway and of the survivor activating factor enhancement 23 . The connection between the tissue where the intermittent ischemia is performed and the tissue that is under permanent ischemia appears to occur through a neurogenic pathway, mediated by the parasympathetic system 24 .…”