Featured Article: Pharmacological postconditioning with delta opioid attenuates myocardial reperfusion injury in isolated porcine hearts

Abstract

In this study, we found that postconditioning with Deltorphin D significantly improved diastolic relaxation and decreased the incidence of ventricular arrhythmias during early reperfusion. Furthermore, these treated hearts demonstrated increased tissue perfusion after 2 h, suggesting improved microvascular function. Delta opioid agonists attenuated reperfusion injury, suggestive of a postconditioning effect. Such agents may have a potential role in minimizing reperfusion injury associated with coronary stenting, bypass surgery, myocardial infarction, cardiac transplantation, or with the utilization of heart preservation systems. AbstractIschemic preconditioning has been utilized to protect the heart from ischemia prior to ischemia onset, whereas postconditioning is employed to minimize the consequences of ischemia at the onset of reperfusion. The underlying mechanisms and pathways of ischemic pre-and postconditioning continue to be investigated as therapeutic targets. We evaluated the administration of a delta opioid agonist or cariporide on various parameters associated with myocardial reperfusion injury upon reperfusion of isolated porcine hearts. The hearts were reperfused in vitro with a Krebs buffer containing either: (1) 1 mM Deltorphin D (delta opioid specific agonist, n ¼ 6); (2) 3 mM cariporide (sodium-hydrogen exchange inhibitor, n ¼ 4); or (3) no treatment (control, n ¼ 6). Subsequently, postischemic hemodynamic performance, arrhythmia burden, relative tissue perfusion, and development of necrosis were assessed over a 2 h reperfusion period. Postconditioning with Deltorphin D significantly improved diastolic relaxation (Tau, P < 0.05 versus controls) and decreased the incidence of ventricular arrhythmias during early reperfusion. Additionally, these treated hearts demonstrated increased tissue perfusion after 2 h (P < 0.05 versus controls), suggesting improved microvascular function. Delta opioid agonists elicited the potential to attenuate reperfusion injury, suggesting a postconditioning effect of these agents. We hypothesize that the induced benefits of delta opioids, in part, are associated with decreased calcium influx on reperfusion, independent of sodium-hydrogen exchange inhibition. Such agents may have a potential role in minimizing reperfusion injury associated with coronary stenting, bypass surgery, myocardial infarction, cardiac transplantation, or with the utilization of heart preservation systems.

Ginsenoside Rb1 for Myocardial Ischemia/Reperfusion Injury: Preclinical Evidence and Possible Mechanisms

“…Abrupt restoration therapy of coronary flow can lead to reversible impairment of myocardial contractility (myocardial stunning), ventricular arrhythmias, and microvascular dysfunction. The pattern of injury that is inflicted on the myocardium has been termed as myocardial ischemia/reperfusion (I/R) injury [5], and the accumulating deleterious effects lead to myocyte necrosis and impaired cardiomyocyte healing, eventually contributing to heart failure associated with other poor outcomes [6]. Consequently, it remains a priority to seek new cardioprotective strategies to improve myocardial salvage and cardiac function.…”

Pharmacological postconditioning: a molecular aspect in ischemic injury

“…The administration of drugs that mimics the mechanism of iPoCo is referred to pPoCo. [ 53 ] Similar to iPreCo, it has been seen that iPoCo cannot be directly applied to an organ which is already exposed to a high‐grade ischaemia. [ 40 ] Other challenges associated with induction of iPoCo are accessibility of the blood vessel for inducing ischaemia and whether reperfusion is achievable or not.…”

Consideration of appropriate clinical applications for cardiac xenotransplantation

“…90 Improvements in organ preservation and intensive care practices, as well as diminishing early xenospecific inflammatory responses, have shown to be efficacious in reducing PCXD. [93][94][95][96] [93][94][95][96] …”

“…91,92 Further optimization of these concepts in perioperative management, and the use of additional cardioprotective maneuvers, such as remote ischemic preconditioning, metabolic support, and pharmacologic administration, may also be required to minimize PCXD. [93][94][95][96]…”