A unified concept of the pathophysiology of myocardial infarction and sudden death.

he mechanism of myocardial infarction and Tunexpected sudden cardiac death remains incompletely defined. The frequent absence of complete coronary arterial obstruction in both these conditions' has challenged the concept of arterial obstruction followed by infarction or sudden death or both. Several independent observations are herein developed into a working hypothesis for the pathogenesis of myocardial infarction and sudden death. This is based upon the unique anatomic, pathologic and physiologic features of the heart during infarction and unexpected sudden death. The two major morphologic types of infarction are transmural ( 40 percent ) and subendocardial (60 percent). The former almost always occurs in the presence of arterial obstruction (90 percent); the latter usually occurs in the presence of diseased, though patent, coronary arteries.' Fresh transmural infarcts may be associated with new or old occlusions. Such occlusions are usually divided equally between fibrin thrombosis and hemorrhage into an atheromatous plaque. Furthermore, old occlusions are frequently noted (44 percent) in the hearts of individuals who have died of noncardiac causes in the absence of any pathologic evidence for myocardial necrosis.' Thus, we are challenged to explain the mechanism of new infarction or sudden death in the presence or absence of occlusion and to explain the absence of infarction in the presence of major arterial obstruction. Several remarkable and unique features of the heart must be noted. Contrary to current opinion, the heart is not an end-arterial system' lending itself readily to infarction secondary to coronary arterial obstruction. A rich system of collateral vessels pervades the subendocardium and interconnects with the penetrating large extramural coronary arterial system (Fig 1). Thus, occlusion in the extramural system would not necessarily be followed by infarction and, as has been described by Baroldi and Scomazzoni,* it often is not. It is necessary, however, to be cognizant of the frequency with which subendocardial necrosis occurs despite elaborate collateral circulation and major coronary arterial patency. Certain features of the subendocardium render it the most frequent area of the heart to undergo necrosis in pathophysiologic states that are unfavorable to balancing myocardial demand and oxygen supply. For example, by direct measurements it has the lowest tissue partial pressure of oxygen of any organ of the body and of any layer of the hearte3 Stress measurements are highest4 and myofibril length the longest5 in the subendocardium thereby making oxygen demand the greatest. The 'From the University of Nebraska Hospitals and University capillary bed is at near capacity utilization at rest of Nebraska Medical Center, Omaha. '*Director, Division of Cardiology, University of Nebraska and is entirely unperfused during sy~tole .~ Thus Hospitals; Professor of Medicine, University of Nebraska there is evidence for the inordinate predisposition of Medical Center. tChief, Cardiology Section, Veterans Administration Hosthe subendocardium to undergo necrosis as well as pita]; Assistant Professor of Medicine, University of the likelihood of its involvement in unexpected Nebraska Medical Center. Reprint requests: Dr. Eliot, Unioersity of Nebraska Medical sudden cardiac death. It should be recalled that all Center, Onlaha 68154. transmural infarcts by definition involve the suben-