Background-Ischemic preconditioning reduces local tissue injury caused by subsequent ischemia-reperfusion (IR), but may also have a salutary effect on IR injury of tissues remote from those undergoing preconditioning. We tested the hypothesis that limb ischemia induces remote preconditioning, reduces endothelial IR injury in humans, and reduces experimental myocardial infarct size. Methods and Results-Endothelial IR injury of the human forearm was induced by 20 minutes of upper limb ischemia (inflation of a blood pressure cuff to 200 mm Hg) followed by reperfusion. Remote preconditioning was induced by three 5-minute cycles of ischemia of the contralateral limb. Venous occlusion plethysmography was used to assess forearm blood flow in response to acetylcholine at baseline and 15 minutes after reperfusion. Experimental myocardial infarction was achieved by 40 minutes of balloon occlusion of the left anterior descending artery in 15-kg pigs. Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Triphenyltetrazolium staining was used to assess the extent of myocardial infarction. In the human study, the response to acetylcholine was significantly attenuated in the control group after 15 minutes' reperfusion, but remote preconditioning prevented this reduction. Limb ischemia caused a significant reduction in the extent of myocardial infarction relative to the area at risk compared with control (26Ϯ9% versus 53Ϯ8%, PϽ0.05). Key Words: endothelium Ⅲ ischemia Ⅲ reperfusion Ⅲ ischemic preconditioning, remote I schemia-reperfusion (IR) complicates myocardial infarction and stroke and contributes to the associated tissue injury and mortality; reducing IR injury may improve the outcome of reperfusion therapy for these conditions. 1 One successful approach in the experimental setting is ischemic preconditioning (IPC), whereby prior sublethal ischemia induces a state of protection against subsequent prolonged IR. 2 Although animal studies have shown that protection occurs locally in the tissue being preconditioned, systemic effects of localized IPC have been observed. 3 This raises the possibility that regional ischemia of accessible nonvital tissues might protect remote vital organs undergoing IR, and some data support this in humans. 4 In the present study we tested the hypothesis that short periods of limb ischemia induce remote preconditioning and reduce IR injury in vivo. We used a human model of endothelial IR injury to test whether remote limb ischemia induces systemic preconditioning in humans. Furthermore, we studied an experimental model of myocardial infarction to characterize whether limb ischemia reduced myocardial IR injury.
Conclusion-Remote
Methods Study 1: Remote Preconditioning of Human Endothelium by Contralateral Limb Ischemia
Subjects and Study DesignFourteen healthy volunteers, with a mean age of 33 (range, 26 to 52) years, gave informed signed consent and were randomized to remote preconditioning and control groups. Studies were approved by the local Research Ethics Committ...
We previously described a method for regional myocardial cooling that reaches the target temperature within 4 min. The present study evaluated whether this method for regional myocardial cooling during reperfusion reduces myocardial infarct size (IS) in 75-kg pigs. Myocardial infarction was induced by inflation of an angioplasty balloon in the left anterior descendent artery for 45 min followed by 3 h reperfusion. First, 15 pigs were randomized to regional myocardial cooling during reperfusion (n = 8) or control (n = 7). As further control experiments, systemic hypothermia was induced prior to ischemia (n = 3) and during reperfusion (n = 3). IS and area at risk (AAR) were evaluated in vivo by single photon emission cardiac tomography (SPECT) and by standard histochemical staining. Regional cooling during reperfusion did not reduce IS/AAR as assessed by histochemistry (cooling: 0.71 +/- 0.8; control: 0.68 +/- 0.10; p = ns) and SPECT (cooling: 0.90 +/- 0.20; control: 0.88 +/- 0.32; p = ns). Systemic hypothermia during ischemia reduced IS/AAR (histochemistry: 0.09 +/- 0.11; SPECT: 0.25 +/- 0.22; p < 0.001 and p = 0.01 vs control, respectively). Induction of systemic hypothermia during reperfusion had no significant effect on IS/AAR (histochemistry: 0.63 +/- 0.07; SPECT: 0.74 +/- 0.09; p = ns vs control for both comparisons). In conclusion, hypothermia during ischemia is strongly myocardioprotective while hypothermia during reperfusion does not reduce myocardial infarct size in human-sized pigs.
Background: Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with Liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model.
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