The Reduction of Infarct Size — An Idea Whose Time (For Testing) Has Come

An Idea Whose Time (For Testing) Has Come EARLY IN THIS CENTURY, cardiovascular physiologists began to direct their attention to the study of the control of myocardial oxygen con- sumption (MVO2).Evans and Matsuoka, in Starling's laboratory in London,' and Rohde, in Heidelberg,2 called attention to the importance of intraventricular pressure as a principal determinant of M'/O2.Technical developments during subsequent decades allowed a systematic reexamination of this problem in the mid-1950s,3 resulting in more precise elucidation of the role of intraventricular tension, myocardial fiber shortening, contraction frequency, and external car- diac work in regulating the heart's oxygen needs.Later, the roles of myocardial contractility,4 the basal oxygen needs of the noncontracting heart,5 the costs of electrical depolarization of the myocardium,6 and the effect of shortening against a load7 on MVO2 were defined.8While of considerable interest to physiologists, an understanding of the determinants of MVO2 has con- siderable clinical implications as well.After all, myocardial ischemia, the principal consequence of coronary arteriosclerosis, is characterized by an im- balance between myocardial oxygen needs and availability, which results in chest discomfort, as well as in alterations in the electrical, mechanical, and metabolic properties of the heart.Persistent, severe ischemia, of course, results in myocardial necrosis.Armed with an understanding of the determinants of MVO2, it seemed like a logical step to determine whether altering the relation between myocardial energy supply and demand might actually influence the severity and extent of ischemic injury, as well as the extent of actual myocardial necrosis following cor- onary occlusion.9'Utilizing a technique for epicar- dial electrocardiography, combined with myocardial enzyme (CPK) determinations,1' histologic, histochemical, and electronmicroscopic'2 analysis of cardiac muscle, it soon became clear that following coronary occlusion, interventions which augment Mv02 increase the extent and severity of ischemic in- jury and ultimately the quantity of necrotic tissue."