Postconditioning Protects Against Endothelial Ischemia-Reperfusion Injury in the Human Forearm

Abstract

Background-Hypoxic cell death follows interruption of blood supply to tissues. Although successful restoration of blood flow is mandatory for salvage of ischemic tissues, reperfusion can paradoxically place tissues at risk of further injury. Brief periods of ischemia applied at the onset of reperfusion have been shown to reduce ischemia-reperfusion (IR) injury, a phenomenon called postconditioning. The aim of this study was to determine whether postconditioning protects against endothelial IR injury in humans, in vivo. Methods and Results-Brachial artery endothelial function was assessed by vascular ultrasound to measure flow-mediated dilation (FMD) in response to forearm reactive hyperemia. FMD was measured before and after IR (20 minutes of arm ischemia followed by 20 minutes of reperfusion) in healthy volunteers. To test the protective effects of postconditioning, 3 cycles of reperfusion followed by ischemia (each lasting 10 or 30 seconds) were applied immediately after 20 minutes of arm ischemia. To determine whether postconditioning needs to be applied at the onset of reperfusion, a 1-minute period of arm reperfusion was allowed before the application of the 10-second postconditioning stimulus. IR caused endothelial dysfunction (FMD 9.1Ϯ1.2% pre-IR, 3.6Ϯ0.7% post-IR, PϽ0.001; nϭ11), which was prevented by postconditioning applied as 10-second cycles of reperfusion/ischemia (FMD 9.9Ϯ1.7% pre-IR, 8.3Ϯ1.4% post-IR, PϭNS; nϭ11) and 30-second cycles of reperfusion/ischemia (FMD 10.8Ϯ1.7% pre-IR, 9.5Ϯ1.5% post-IR, PϭNS; nϭ10) immediately at the onset of reperfusion. No protection was observed when the application of the 10-second postconditioning stimulus was delayed for 1 minute after the onset of reperfusion (FMD 9.8Ϯ1.2% pre-IR, 4.0Ϯ0.9% post-IR, PϽ0.001; nϭ8). Key Words: endothelium Ⅲ ischemia Ⅲ reperfusion Ⅲ reperfusion injury Ⅲ postconditioning T he prerequisite for salvage of viable myocardium and limitation of infarct size after an acute ischemic event is timely reperfusion. 1,2 However, restoration of coronary blood flow carries with it the risk of further myocardial injury (reperfusion injury). 3 Events occurring during reperfusion have been shown to be responsible in part for reversible (stunning) and, more important, lethal (necrosis/apoptosis) injury in animal models. 4 -7 Although the contribution of reperfusion injury to infarct size in humans is unknown, it is possible that minimizing reperfusion injury might reduce infarct size in humans. Conclusions-This Clinical Perspective p 1019Modulating blood flow on reperfusion (through gradual or intermittent reperfusion) has been shown to reduce experimental infarct size. 8,9 In particular, Vinten-Johansen et al 10 have shown that a schedule of intermittent reperfusion (termed "postconditioning") applied at the onset of reperfusion reduces infarct size in animal models of myocardial ischemia-reperfusion (IR) injury. The protective effect of postconditioning is of a similar magnitude to that seen with ischemic preconditioning. 11 However, unlike precondi...

Ischemic pre and postconditioning in skeletal muscle injury produced by ischemia and reperfusion in rats

“…In humans, this effect is described in the heart 5 , brain 6 , kidneys 7 , liver 8 and skeletal muscle 9 . Ischemic postconditioning, which consists on producing short periods of ischemia and reperfusion just before sustained reperfusion, also produced protective effects in rats 10 , rabbits 11 , pigs 12 and humans 13 .…”

Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage

“…16 Experimental and clinical studies have indicated the protective effects of postconditioning in ischaemia/reperfusion injury. [17][18][19][20][21] This protection is not only associated with inhibition of inflammation and apoptosis, 22,23 but also with attenuation of oxidative stress. 3,24 The aim of the present study was to use a rat model of ischaemia/ reperfusion injury to evaluate the effects of ischaemic postconditioning on mitochondrial ROS production, in order to determine whether its inhibitory effects on oxidative stress are mediated via the mitochondrial pathway, since the golgi apparatus is also a source of ROS.…”

Ischemic postconditioning does not improve peripheral endothelial function in ST-segment elevation myocardial infarction patients

“…Several studies have explored the influence of IPC on endothelial function in human models of forearm ischemia-reperfusion (IR) injury with mixed results. [16][17][18] In 11 healthy volunteers brachial FMD was measured before and after IR (20 minutes of arm ischemia followed by 20 minutes of reperfusion). 16 IR caused endothelial dysfunction (FMD 9.1 ± 1.2% pre-IR, 3.6 ± 0.7% post-IR, p < 0.001), which was prevented by three 10-second cycles (FMD 9.9 ± 1.7% pre-IR, 8.3 ± 1.4% post-IR, p = NS) or three 30-second cycles of postconditioning (FMD 10.8 ± 1.7% pre-IR, 9.5 ± 1.5% post-IR, p = NS).…”