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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...

Several lines of evidence indicate that pre-fibrillar assemblies of amyloid- (A)polypeptides

Background-We have demonstrated that myocardial acceleration during isovolumic contraction (IVA) is a sensitive index of left ventricular contractile function. In this study, we assessed the utility of IVA to measure right ventricular (RV) contractile function. Methods and Results-We examined 8 pigs by using tissue Doppler imaging of the RV free wall and simultaneous measurements of intraventricular pressure, volume, maximal elastance (e max ), preload recruitable stroke work, and dP/dt max by conductance catheterization. Animals were paced in the right atrium at a rate of 130 beats per minute (bpm).IVA was compared with elastance during contractility modulation by esmolol and dobutamine and during preload reduction and afterload increase by transient balloon occlusion of the inferior vena cava and pulmonary artery, respectively. Data were also obtained during incremental atrial pacing from 110 to 210 bpm. Esmolol led to a decrease in IVA and dP/dt max . During dobutamine infusion, IVA, dP/dt max , preload recruitable stroke work, and e max all increased significantly. During preload reduction and afterload increase, IVA remained constant up to a reduction of RV volume by 54% and an RV systolic pressure increase of 58%. Pacing up to a rate of 190 bpm led to a stepwise increase in IVA and dP/dt max , with a subsequent fall at a pacing rate of 210 bpm. Conclusions-IVA is a measurement of RV contractile function that is unaffected by preload and afterload changes in a physiological range and is able to measure the force-frequency relation. This novel index may be ideally suited to the assessment of acute changes of RV function in clinical studies.

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