Alternative Pharmacological Interventions that Limit Myocardial Infarction

Abstract

Despite current optimal treatment, the morbidity and mortality of coronary heart disease remain significant worldwide and open the way for the development of novel cardioprotective therapies. In the last two decades, a remarkable scientific effort has focused on the limitation of infarct size. Important input from experimental studies has led the way in this direction. However, clinical and preclinical results using various cardioprotective strategies to attenuate reperfusion injury have generally not been applicable for every day clinical practice. Protection of the ischemic myocardium is known to occur as a result of ischemic preconditioning (PC), in which repetitive brief periods of ischemia protect the heart from a subsequent prolong ischemic insult. Although PC is a powerful form of protection, it is of limited clinical application for obvious ethical and practical reasons. Another endogenous form of cardioprotection, similar to PC but applicable at the time of reperfusion, termed postconditioning (PostC), has been recently described. Short series of repetitive cycles of brief reperfusion and re-occlusion of the coronary artery applied at the onset of reperfusion, reduce the infarct size and coronary artery endothelial dysfunction. At present, pharmacological PC and PostC are possible alternative methods that may substitute pharmaceutical treatments the short ischemic insults. Adenosine, nicorandil and other agents have been already used as pharmacological mimetics of ischemic PC in multicenter trials. We summarize the recent research efforts on novel therapeutic strategies and on the design of new compounds, based on the accumulated knowledge of the ligands, receptors and intracellular signaling pathways of PC and PostC.

ATP-Sensitive Potassium Channel Activation Induces Angiogenesis In Vitro and In Vivo

“…The present results also imply that the benefit of nicorandil's use in the treatment of ischemic heart disease (Andreadou et al, 2008;Horinaka, 2011) and its effects in ischemic preconditioning in humans (Matsubara et al, 2000) may also be attributable, in addition to vasodilatation, to endothelial protective effects. Furthermore, our results present some intriguing implications regarding the use of K ATP inhibitors (sulfonylureas) in diabetes.…”

Mechanisms Involved in Cardioprotective Effects of Pravastatin Administered during Reoxygenation in Human Myocardium In Vitro

“…However, myocyte cell death is temporarily enhanced by reperfusion, a phenomenon referred to as "reperfusion injury." 1,2 Increasing research has focused on limiting reperfusion-induced injury, which could result in increased salvage of ischemic myocardium and possibly improved mortality and morbidity. 1,2 Statins have been reported to have pleiotropic effects beyond their cholesterol-lowering effects.…”

“…1,2 Increasing research has focused on limiting reperfusion-induced injury, which could result in increased salvage of ischemic myocardium and possibly improved mortality and morbidity. 1,2 Statins have been reported to have pleiotropic effects beyond their cholesterol-lowering effects. 3 Statins may be considered a global perioperative protective therapy for patients undergoing major vascular surgery 4 and have been shown to reduce the risk of perioperative myocardial ischemia.…”

Chick Embryo: A Preclinical Model for Understanding Ischemia-Reperfusion Mechanism

“…Although many notable drug development achievements have been made in the last two decades in ischemic research, a key challenge in drug candidate screening is the lack of a suitable screening model, which can translate preclinical drug candidates into clinical success ( Andreadou et al, 2008 ; Bahjat et al, 2017 ). In this study, we critically evaluated the role anti-oxidative, anti-ischemic, and anti-inflammatory drugs after 6 h of I/R.…”