Protection of organs other than the heart by remote ischemic conditioning

Organ or tissue dysfunction due to acute ischemia–reperfusion injury (IRI) is the leading cause of death and disability worldwide. Acute IRI induces cell injury and death in a wide variety of organs and tissues in a large number of different clinical settings. One novel therapeutic noninvasive intervention, capable of conferring multiorgan protection against acute IRI, is ‘remote ischemic conditioning’ (RIC). This describes an endogenous protective response to acute IRI, which is triggered by the application of one or more brief cycles of nonlethal ischemia and reperfusion to one particular organ or tissue. Originally discovered as a therapeutic strategy for protecting the myocardium against acute IRI, it has been subsequently demonstrated that RIC may confer protection against acute IRI in a number of different noncardiac organs and tissues including the kidneys, lungs, liver, skin flaps, ovaries, intestine, stomach and pancreas. The discovery that RIC can be induced noninvasively by applying the RIC stimulus to the skeletal tissue of the upper or lower limb has facilitated its application to a number of clinical settings in which organs and tissues are at high risk of acute IRI. In this article, we review the experimental studies that have investigated RIC in organs and tissues other than the heart, and we explore the therapeutic potential of RIC in preventing organ and tissue dysfunction induced by acute IRI

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

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

Cardiac troponins and volatile anaesthetics in coronary artery bypass graft surgery: A systematic review, meta-analysis and trial sequential analysis

BACKGROUND: Reports from animal studies indicate that volatile anaesthetics protect the myocardium against the effects of acute ischaemia-reperfusion injury by reducing infarct size. This cardioprotective effect in the clinical setting of coronary artery bypass graft (CABG) surgery, where the heart is subjected to global ischaemia-reperfusion injury, remains controversial. OBJECTIVE: The objective was to demonstrate that clinical studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in CABG are no longer warranted. We also investigated the effect of volatile anaesthetics on cardiac enzymes in off-pump cardiac surgery. DESIGN: Systematic review of randomised clinical trials, meta-analyses and trial sequential analysis (TSA). DATA SOURCES: Trials between January 1985 and March 2015 were obtained from electronic databases (Medline, Excerpta Medica Database (EMBASE), Cochrane Controlled Trial Register, abstracts from major anaesthesiology and cardiology journals and reference lists of relevant randomised trials and review articles. ELIGIBILITY CRITERIA: Relevant randomised clinical trials were included. We investigated the effect of volatile anaesthetics in both off-pump and on-pump CABG surgery with respect to troponin release [peak postoperative cardiac troponin I (cTnI) and cardiac troponin T (cTnT), cTnI/cTnT] and performed two separate meta-analyses. TSA was used to overcome the weakness of a type-1 error associated with repeated meta-analyses. RESULTS: From 30 studies, 2578 patients were pooled for the meta-analysis. The outcome significantly favours the use of peroperative volatile over non-volatile anaesthetics during on-pump CABG surgery with regard to peak postoperative cTnI (0.995 mg l; standard mean difference, 95% confidence interval, -1.316 to -0.673; P < 0.001). Meta-analysis of 11 off-pump studies showed no difference in peak postoperative cTnI (0.385 mg l; standard mean difference, 95% confidence interval, -0.857 to 0.087; P = 0.11). TSA indicated that the required information size for on-pump surgery was 1072 patients, and for off-pump surgery it was 1442; this latter figure has not yet been reached. CONCLUSION: Studies investigating the cardioprotective effect of volatile anaesthetics on cardiac troponins in on-pump CABG surgery are no longer warranted. This is not yet the case for off-pump surgery

Parkinson's disease proteins: Novel mitochondrial targets for cardioprotection

Ischemic heart disease (IHD) is the leading cause of death and disability worldwide. Therefore, novel therapeutic targets for protecting the heart against acute ischemia/reperfusion injury (IRI) are required to attenuate cardiomyocyte death, preserve myocardial function, and prevent the onset of heart failure. In this regard, a specific group of mitochondrial proteins, which have been linked to familial forms of Parkinson's disease (PD), may provide novel therapeutic targets for cardioprotection. In dopaminergic neurons of the substantia nigra, these PD proteins, which include Parkin, PINK1, DJ-1, LRRK2, and α-synuclein, play essential roles in preventing cell death-through maintaining normal mitochondrial function, protecting against oxidative stress, mediating mitophagy, and preventing apoptosis. These rare familial forms of PD may therefore provide important insights into the pathophysiology underlying mitochondrial dysfunction and the development of PD. Interestingly, these PD proteins are also present in the heart, but their role in myocardial health and disease is not clear. In this article, we review the role of these PD proteins in the heart and explore their potential as novel mitochondrial targets for cardioprotection

Remote Ischemic Conditioning in Emergency Medicine—Clinical Frontiers and Research Opportunities

Time-critical acute ischemic conditions such as ST-elevation myocardial infarction and acute ischemic stroke are staples in Emergency Medicine practice. While timely reperfusion therapy is a priority, the resultant acute ischemia/reperfusion injury contributes to significant mortality and morbidity. Among therapeutics targeting ischemia/reperfusion injury (IRI), remote ischemic conditioning (RIC) has emerged as the most promising.RIC, which consists of repetitive inflation and deflation of a pneumatic cuff on a limb, was first demonstrated to have protective effect on IRI through various neural and humoral mechanisms. Its attractiveness stems from its simplicity, low-cost, safety, and efficacy, while at the same time it does not impede reperfusion treatment. There is now good evidence for RIC as an effective adjunct to reperfusion in ST-elevation myocardial infarction patients for improving clinical outcomes. For other applications such as acute ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, cardiac arrest, and spinal injury, there is varying level of evidence.This review aims to describe the RIC phenomenon, briefly recount its historical development, and appraise the experimental and clinical evidence for RIC in selected emergency conditions. Finally, it describes the practical issues with RIC clinical application and research in Emergency Medicine