The Effects of Carbon Monoxide Releasing Molecules (CO-RMS) in Myocardial Inotropy and Protection Against Ischaemia-Reperfusion Injury

Myocardial ischaemia reperfusion injury is common in clinical prac.tice. Myocardial infarction is a good example, in which prolonged coronary artery occlusion by a thrombus may be followed by reperfusion either spontaneously or by medical intervention with thrombolytic drugs or acute angioplasty. The heart may also undergo ischaemia-reperfusion during operations that require temporary interruption of myocardial blood supply s~ch as, coronary artery bypass grafting and heart transplantation. Carbon monoxide, one of the products of haem degradation by the enzyme haem oxygenase, has been shown to protect the myocardium against reperfusion injury and confer other desirable effects despite the bad historical reputation it always had (the silent killer and waste product). Special molecules (COtRMs) capable of carrying carbon monoxide and releasing it in physiological solution have been developed to facilitate further investigation of the role of this gas in biosystems under physiological and pathological conditions and to provide the basis for potential therapeutic agent in the future. The aims of this study are to examine: 1) the effects of CO-RMs on hearts perfused under normal physiologic conditions; 2) the mechanism of the positive inotropic effect induced by some CORMs; 3) to test CO positive inotropic action in failing rat hearts; 4) to study the ability of CO-RMs these molecules to protect against ischaemia-reperfusion injury in models resembling myocardial infarction and heart cold preservation. Results demonstrated for the first time that CO-RM possess positive inotropic effects, and that protection was afforded by the drug against myocardial IIR.EThOS - Electronic Theses Online ServiceGBUnited Kingdo