From pump to molecules.

Abstract

In response to Eduardo Marban’s invitation to prepare a brief reminiscence on the occasion of the 50th anniversary of Circulation Research , I recount here a few of the ideas and events that have marked my 47 years in research. My research career began when, fresh from a surgical internship at the Johns Hopkins Hospital, I arrived at the then National Heart Institute in 1956. There, having watched Andrew Morrow perform transbronchial left heart catheterization, I thought there must be a better way. I soon became immersed in developing a method for transseptal left heart catheterization, first in dogs, then in human cadavers, and finally in patients; thus, my first research experience proved to be “translational.” It was satisfying to later see this approach used for balloon mitral valvuloplasty and in cardiac electrophysiology. In the early 1960s, there was considerable ferment in the Cardiology Branch of the National Heart Institute in Bethesda within a group of investigators brought together by Eugene Braunwald, one important aspect of which concerned cardiac function. We discussed the current state of cardiac physiology, comparing the approach of Robert Rushmer in intact animals with that of Stanley Sarnoff in the tightly regulated isolated supported heart. Playfully, we formulated two laws of the heart: Rushmer’s Law “When nothing is held constant everything changes” and Sarnoff’s Law “When everything is held constant nothing changes.” Stimulated primarily by the work of Ed Sonnenblick (then at the NIH), I pondered how we might begin to apply the principles of isolated muscle mechanics to the intact heart using an approach in which only one component of an otherwise intact system is perturbed. Assisted by Jim Covell, a method was devised for assessing cardiac function that involved sudden changes in aortic pressure during a single diastolic interval so that the subsequent heartbeat …