title: Is further improvement of the treatment of acute coronary syndromes still possible?
abstract: Successful treatment of myocardial infarction related to early reperfusion therapy has caused growing interest in not only ischemic but also myocardial reperfusion injury. Most experimentally confirmed preservation myocardial reperfusion injury methods have failed in clinical practice. Probably one reason for their ineffectiveness was the very narrow "time window" necessitating application of protective methods before obtaining reperfusion. Reducing the myocardial necrosis and preservation of the left ventricular function are the main goals of the therapy. Experimental data suggest that up to 50% of the infarct size may be related to reperfusion injury. Function of the mitochondrial permeability transition pore (mPTP) in the inner mitochondrial membrane, being closed during myocardial ischemia and opening at the beginning of reperfusion, is the common element linking protective methods. Their opening gives rise to metabolic alterations and may lead to cardiomyocyte death (lethal reperfusion injury). That is why successful intervention, very difficult to achieve, has to take precedence over coronary blood flow restoration. Cyclosporin A, an mPTP blocker, was effective in the first small clinical trial in preservation of myocardial reperfusion injury in acute coronary syndrome intervention. Second mitochondrial injury action is related to generation of reactive oxygen species (ROS) including superoxide anions. Reactive oxygen species accumulation results in mitochondrial pH increase leading to mPTP opening. Discovery of a small molecule cationic peptide, readily penetrating cell membranes and concentrating in mitochondria, may give new therapy perspectives. Combining therapy may be possible as well.
authors.affiliation: Cardiology Clinic, Physiotherapy Division, 2 Faculty of Medicine, Bielanski Hospital, Medical University of Warsaw, Poland.
authors.forename: Marek Jerzy
authors.initials: MJ
authors.lastname: Dąbrowski
keywords: Bendavia; cyclosporin A; myocardial infarction; reactive oxygen species; reperfusion