Perioperative Cardioprotection: General Mechanisms and Pharmacological Approaches

Abstract

Cardioprotection encompasses a variety of strategies protecting the heart against myocardial injury that occurs during and after inadequate blood supply to the heart during myocardial infarction. While restoring reperfusion is crucial for salvaging myocardium from further damage, paradoxically, it itself accounts for additional cell death—a phenomenon named ischemia/reperfusion injury. Therefore, therapeutic strategies are necessary to render the heart protected against myocardial infarction. Ischemic pre- and postconditioning, by short periods of sublethal cardiac ischemia and reperfusion, are still the strongest mechanisms to achieve cardioprotection. However, it is highly impractical and far too invasive for clinical use. Fortunately, it can be mimicked pharmacologically, for example, by volatile anesthetics, noble gases, opioids, propofol, dexmedetomidine, and phosphodiesterase inhibitors. These substances are all routinely used in the clinical setting and seem promising candidates for successful translation of cardioprotection from experimental protocols to clinical trials. This review presents the fundamental mechanisms of conditioning strategies and provides an overview of the most recent and relevant findings on different concepts achieving cardioprotection in the experimental setting, specifically emphasizing pharmacological approaches in the perioperative context.

Ischemic preconditioning protects the heart against ischemia-reperfusion injury in chronic kidney disease in both males and females

“…Preinfarction angina, warm-up phenomenon, and transluminal coronary angioplasty are considered clinical equivalents of IPRE [ 14 ]. Although IPRE confers remarkable cardioprotection in a variety of species [ 15 , 16 ], including humans [ 17 – 19 ], we and others have shown in pre-clinical and clinical studies that its effectiveness is attenuated by age [ 14 ] and some co-morbidities, such as hypercholesterolemia [ 18 , 20 , 21 ] and diabetes mellitus [ 22 – 24 ]. However, some pre-clinical studies on CKD using male animals suggest that despite the complex systemic metabolic changes in CKD, cardioprotection by IPRE is still preserved.…”

Influence of Hyperglycemia and Diabetes on Cardioprotection by Humoral Factors Released after Remote Ischemic Preconditioning (RIPC)

“…Coronary revascularization after myocardial infarction, along with resupply of oxygen to the myocardium, is crucial for patient survival. Paradoxically, during reperfusion, a cascade of complex cellular processes is triggered by restored blood supply, including electrolyte shift, as well as release of intracellular enzymes and proapoptotic factors, resulting in cardiomyocyte damage and death [8]. This phenomenon of myocardial damage due to restored coronary perfusion is called ischemia/reperfusion (I/R) injury and accounts for up to 50% of the final infarct size [9].…”

Perioperative Kardioprotektion – „From bench to bedside“

“…2; [6,7]). An dieser Stelle sind insbesondere der Reperfusion-injury-salvagekinase(RISK)und Survivor-activatingfactor-enhancement(SAFE)-Signalweg hervorzuheben, welche untereinander interagieren und das Mitochondrium als Endeffektor beeinflussen [5,8,9].…”

“…2 8 Vereinfachte schematische Darstellung der zugrunde liegenden kardioprotektiven Signalwege, mit Fokus auf "reperfusion injury salvage kinase" (RISK) und "survivor activating factor enhancement" (SAFE). (Modifiziert nach Heusch [10] und Torregroza et al [5])…”