Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway

Weinbrenner, Christof; Nelles, Manfred; Herzog, Nicole; Sárváry, László; Strasser, Ruth H.

doi:10.1016/s0008-6363(02)00446-7

Cited by 128 publications

(109 citation statements)

References 30 publications

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“…Although it was first described in the 1990s and was shown in multiple species to be a universal phenomenon with systematic protective effects affecting multiple organs, no exact mechanisms have been defined [11,12]. In many ways, it resembles local ischaemic preconditioning with the same kinases [13] and changes in mitochondrial function [14] being involved; however, the exact nature of signal transduction from remote tissue to target organ remains to be fully elucidated. Both humoral and neuronal pathways have been proposed [15].…”

Section: Discussionmentioning

confidence: 99%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

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A b s t r a c tBackground: Remote preconditioning has been shown to be a potent protective phenomenon in many animals. Several studies aimed to demonstrate it was feasible in humans by trying to show its protective effect during cardiac surgery. Of these, some small studies and one larger trial were positive while two other bigger studies showed no effectiveness of remote preconditioning as assessed by levels of postoperatively released cardiac markers. Recently, two large clinical trials also failed to prove the benefit of remote preconditioning in cardiac surgery. No study showed that remote preconditioning actually increases resistance of human myocardium to standardised ischaemic and reperfusion stimulus in experimental settings. In animal studies, remote preconditioning was shown to improve mitochondrial function and structure, but such data on human myocardium are scarce. Aim:The aim of the study is to determine whether remote preconditioning protects human myocardium against ischaemia-reperfusion injury in both in vivo and in vitro conditions. Methods:The trial is designed as a single-centre, double-blinded, sham-controlled trial of 120 patients. We randomise (1:1) patients referred for coronary artery bypass grafting for stable coronary artery disease to remote preconditioning or "sham" intervention. The remote preconditioning is obtained by three cycles of 5 min inflation and 5 min deflation of a blood pressure cuff on the right arm. Postoperative course including myocardial enzymes profile will be analysed. Moreover, in the in-vitro arm the clinically preconditioned myocardium will be assessed for function, mitochondria structure, and mitochondria-dependent apoptosis. The informed consent of all patients is obtained before enrolment into the study by the investigator. The study conforms to the spirit and the letter of the declaration of Helsinki. Results and conclusions:In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the effect can be confirmed in a controlled experimental setting. The study might therefore indicate future directions in trials of clinical implementation of remote preconditioning. INTRODUCTIONNo experimental study showed that human myocardium can be remotely preconditioned against standardised ischaemic/hypoxic insult. We aim to remove this major knowledge gap by applying remote preconditioning to the patient and studying ex-vivo the myocardium obtained thereafter. We assume that we will be able to show that remote preconditioning by brief periods of ischaemia of the arm protects segments of human right atrial appendage myocardium subjected to simulated hypoxia and reoxygenation in-vitro.This proof of principle is crucial. In case the effect of remote preconditioning is not measurable in ex-vivo assessment, any future attempt at implementing this phenomenon in clinical practice may be futile and should not be continued until the e...

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Section: Discussionmentioning

confidence: 99%

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

et al. 2018

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“…Эффект дис-танционного прекондиционирования вследствие ишемии кишки устраняется экзогенными ганглио-блокаторами, капсаицином [54]. Защитный эффект, вызванный ишемией-реперфузией брюшной аорты, не устраняется ганглиоблокаторами [115], однако нельзя исключать нейрогенного влияния. Для орга-нов с богатой сенсорной активацией большое зна-чение имеет активация висцеральных афферентов.…”

Section: Aadsorasunclassified

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

Zarubina

Викторовна²,

Shabanov

et al. 2016

Rev Clin Pharm Drug Ther

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The phenomenon of ischemic preconditioning based on the S.P. Botkin’s idea about defense effect of disturbing factors acting in small intensities is observed in the review. The modern literature data about main types of preconditioning exposure, triggers and mechanisms of ischemic preconditioning are reviewed. This phenomenon was supported in many experiments in vivo and in vitro on animals of different spices as well as in humans in clinical conditions. Ischemic preconditioning is qualified as transient positive changes in the organs and tissues produced by activation of rapid endogenous adoptive processes in them during the short period of subletal ischemia and reperfusion and which defend them from subsequent ischemic episodes. There are early and late ischemic preconditioning (the second window of defense). The first type of ischemic preconditioning belongs to classic type of preconditioning and is produced by the short ischemic episodes (3-5 min) and similar intervals of reperfusion. Ischemic preconditioning observed in a day or more after preconditioning stimuli is named as late preconditioning with genes expression, synthesis of heat shock proteins (HSP 72 in particular) and NO synthase as the basis mechanisms underlying of it. Administration of triggers like adenosine, forbol ether, bradykinine or glycerol derivatives into the blood or ischemic tissues produces defense action similar to ischemic preconditioning and qualified as pharmacological preconditioning. Preconditioning induced by pharmacological agents are more preference than short ischemic episodes. Antihypoxic effects of benzimidazol derivatives in both an acute hypoxia and hypoxic preconditioning are described in the article. Other perspectives of pharmacological preconditioning in practical use are also discussed.

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“…These include the ligand binding to G-protein cell surface coupled receptors such as adenosine [170], bradykinin [171], opioids [172], angiotensin [192], and endocannabinoids [174]. The binding to these cell surface receptors appears to then activate intracellular kinases such as PKC- [184] and other signalling components such as reactive oxygen species [193], nitric oxide and the mitochondrial KATP channel [170]. Whether RIPC also activates pro-survival kinases of the Reperfusion Injury Salvage Kinase (RISK) pathway and results in the inhibition of the mitochondrial permeability transition pore (mPTP), as in IPC and IPost, remains to be determined [164].…”

Section: Myocardial Mechanisms Of Cardioprotection In Ricmentioning

confidence: 99%

Cardioprotection Techniques: Preconditioning, Postconditioning and Remote Con-ditioning (Basic Science)

Hausenloy¹

2013

CPD

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Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. The major pathological consequences of IHD arise from the detrimental effects of acute ischemia-reperfusion injury (IRI) on the myocardium. Therefore, in order to improve clinical outcomes in patients with IHD, novel therapeutic strategies are required to protect the myocardium from acute IRI and preserve cardiac function (cardioprotection). In this regard, endogenous cardioprotective strategies such as ischemic preconditioning (IPC), ischemic postconditioning (IPost) and remote ischemic conditioning (RIC) may provide novel approaches for protecting the heart in clinical settings in which the patient experiences acute myocardial IRI. In this review article, we provide an overview of these endogenous cardioprotective strategies with respect to the pre-clinical experimental literature, exploring their major characteristics and underlying signaling mechanisms. The application of these therapeutic strategies in the clinical setting for potential patient benefit is reviewed in another article in this special issue.

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Remote preconditioning by infrarenal occlusion of the aorta protects the heart from infarction: a newly identified non-neuronal but PKC-dependent pathway

Cited by 128 publications

References 30 publications

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

Remote Ischaemic PrEconditioning of Human Myocardium (RIPE): study protocol for a double-blinded randomised controlled trial

From the S.P. Botkin’s idea of “preexposure” to preconditioning phenomenon. Perspectives for use of phenomena of ischemic and pharmacological preconditioning

Cardioprotection Techniques: Preconditioning, Postconditioning and Remote Con-ditioning (Basic Science)

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