Coronary thrombolysis and the new biology

Abstract

Remarkable progress in the treatment of heart disease is chronicled by the remarks of the distinguished plenary session speakers who have addressed the College during the past 10 years (Table 1). Recently, fibrinolysis has proved to be a particularly powerful means of treating patients with acute myocardial infarction. Accordingly, in this year’s address, it is a privilege to discuss some of the novel and significant contributions of molecular biology to the progress in coronary thrombolysis. Results from Washington University that will be presented reflect vigorous efforts by many colleagues. In addition, we have had extensive help from numerous talented and gracious collaborators from centers throughout the world, such as Desire Cohen at the University of Leuven. To paraphrase John Zinman, a director of the Wills Physics Laboratory of the University of Bristol, they have made our activities in the molecular biology and biochemistry of coronary thrombolysis a joyful experience in the tradition of research he described as “a romance of discovery-a creative enterprise in which the only enemy is ignorance” (I). Coronary thrombolysis is a long-standing concept. Liquefaction of the blood has been recognized for more than a century. The fibrinolytic properties of streptokinase were identified more than 50 years ago. Thus, we must ask, why has enthusiasm been delayed until relatively recently? Several paradigm shifts have punctuated the change. Working with Eugene Braunwald and colleagues at the University of California at San Diego, who demonstrated that infarct size could be reduced by diminution of myocardial oxygen requirements and that infarction was a dynamic process, we and others (2) showed that the extent of infarction was an important determinant of prognosis. In elucidating the phenomenon of coronary spasm, Attilio Maseri and coworkers showed that coronary angiography was safe, even in patients with an acute coronary syndrome. Soon after, Rentrop and colleagues documented recanalization after streptokinase in