Pathophysiology of Coronary Circulation'

Br Heart J: first published as 10.1136/hrt.33.2.173 on 1 March 1971. Downloaded from British Heart Journal, I971, 33, I73-I84. Pathophysiology of coronary circulation' Richard S. Ross2 From The Johns Hopkins University, School of Medicine, *Baltimore, Maryland, U.S.A. I consider it a great honour to have been asked like to quote briefly from the introduction to to give the Sir Thomas Lewis Lecture, and I the first Herter Lecture as follows: have chosen for my subject the pathophysi- ,,ology of the coronary circulation - a topic 'Laboratory methods as applied to the which was of great interest to Sir Thomas. study of clinical medicine have come to stay; reason this is instruments and methods of precision are Another for selecting topic that gradually relieving medicine of its past so much of the good, recent work in this field stigma; they are lifting it to the plane of its * has been done in Britain and many of the sister sciences, its true and proper status. investigators who have made significant con- We have been too content in the past with tfributions are members of this distinguished opinion. In the future we shall rest our case society. This may possibly be a disadvantage upon fact.' (Lewis, I9I5.) m that I will have difficulty saying anything W which is not well known to a large segment of I would like to turn to the subject of my the audience. A third reason for this selection lecture by examining the history of clinical is that ischaemic heart disease is of interest to investigation of ischaemic heart disease. The me and has been the subject of much of the modem era begins with Sir Thomas who in -research with which I have been associated his Billings Lecture in Chicago in I93I sum- during the past nine years. Indeed, the Pro- marized the descriptive observations which Tessorship which I hold at The Johns had gone before and pointed the way for http://heart.bmj.com/ ,,Hopkins University School of Medicine is future studies (Lewis, I932). The first major supported by the Clayton Fund established investigative study on this subject came from _by the late Mr. William L. Clayton and his his department, the Department of Clinical wife to further research in arteriosclerosis, Research at the University College Hospital. especially of the coronary arteries. I refer to the work of Wayne and Laplace Sir Thomas Lewis has been known to me published in Clinical Science in I933. This -through his work throughout my professional represents an important milestone along the life and I have had contact with many of his road to the understanding of the patho- on September 29, 2021 by guest. Protected copyright. ^upils. During the course of preparing this physiology of angina pectoris. This is a lecture I learned that Sir Thomas had come to classic of clinical investigation, and I point to Baltimore in October of 1914 and delivered it as an example of what can be accomplished .1he Herter Lectures at The Johns Hopkins by simple well-designed experiments and Hospital and I was delighted by what I found thoughtful interpretation. This was budget- -irw his introductory remarks (Lewis, I915). less research. Pulse and blood pressure were His words of 55 years ago bear repeating in measured during 400 attacks of chest pain -that they outline the philosophy upon which induced by exercise. Observations of great clinical investigation has moved forward. interest abound in this paper. Of special These remarks indicate to me that Sir interest is the observation of the effect of Thomas would have approved of much of the atropine on exercise tolerance and the onset active investigation of coronary artery disease of pain as depicted in Fig. i. and myocardial infarction, which is currently The investigators measured blood pressure in progress. With your permission I would systolic and diastolic, pulse rate, and the onset The Sir Thomas Lewis Lecture ofthe British Cardiac and cessation of pain. The number of efforts Society I969. Delivered before the annual meeting of ascents over a step are recorded as the ,Qf the British Cardiac Society held at the Royal College height of the vertical bar. The panel at the ofPhysicians, London, 14 November I969. left displays the results of the control experi- m&Susan and William Clayton Professor of Cardio- iscular Disease. The work was supported in part by ment and the comparable observations after USPHS Grants and Contracts, and by Heart Asso- atropine are seen in the right-hand panel. It is ciation of Maryland. readily apparent that the control pulse rate is Br Heart J: first published as 10.1136/hrt.33.2.173 on 1 March 1971. Downloaded from x74 Richard S. Ross higher and the post exercise tachycardia of longer duration after atropine. The patient was able to do only approximately halfas much work after atropine and the pain persisted for a longer time. It is of interest that the blood pressure after atropine was lower than in the control state. These experiments provide a clear demonstration of the importance of pulse rate in the precipitation of angina. This effect has been demonstrated many times since I933 but never with more clarity. The design was simple, the results clear, and hence interpretation was easy. Wayne concluded from the atropine experiments that, 'The diminution in the number of 0 efforts (trips up the steps) and the increase in Minutes the duration of the pain under atropine . .. F I G. I The effect of atropine-induced can be attributed . to the more rapid action tachycardia on exercise tolerance. Observations of the heart, which increases its energy after atropine are shown in the right-hand expenditure without a concomitant increase panel and compared to control observation on in coronary flow......' These atropine experi- the left. The number in the clear vertical ments can be considered to be anticipatory of bar is the number of ascents over a step and the studies with pacing-induced tachycardia the length of the horizontal hatched bar which have occupied many of us in the past represents the duration ofpain. Reproduced few years. from Wayne and Laplace (1933) by permission It is also of note that in this same paper of Clinical Science. Wayne and Laplace reported observations on the effect of mechanical stimulation of the carotid sinus on angina pectoris. Thus, current decade and list coronary arteriography another area of interest in the seventh decade as one of the important developments, but of the century was pioneered in Sir Thomas may well consider it to be important because http://heart.bmj.com/ Lewis' laboratory in the fourth decade. it brought many patients with ischaemic heart disease into the haemodynamic laboratory for study. Before I960, few patients with Haemodynamics of myocardial ischae- coronary heart disease were subjected to haemodynamic evaluation, as such a study In the late I950's the technique of right heart would have been purely investigational and catheterization was applied to the study of without any potential for therapeutic benefit. ii- in angina by Muller and R0rvik (I958) The active investigation of the past five on September 29, 2021 by guest. Protected copyright. Norway and by Johnson, Fairley, and Carter years has contributed to the current concept (i959) in the United States. Both groups of the pathophysiology of myocardial ischae- emphasized the many similarities between mia depicted in Fig. 2 in the form made angina and dyspnoea as manifestations of popular by the systems analyst. The central congestive failure. Both groups recorded in- point of this diagram is the equality between creased pulmonary artery and pulmonary oxygen supply and demand at the cellular capillary wedge pressures in association with level. On the left are the mechanical factors anginal pain. After these two significant that influence demand, heart rate, wall tension, papers, the slow pace of clinical investigation and myocardial contractility. On the right are of ischaemic heart disease continued until the the several factors that influence supply, all of latter half ofthe current decade. Between I965 which are related to blood flow. At the bottom and the present time, many significant papers are listed the manifestations of ischaemia have been published on this subject; this which are the consequences of an imbalance current world-wide epidemic of publication between supply and demand. being attributed to the introduction of three This diagram could be rendered more new techniques. The first is the development comprehensive and hence more complicated of coronary arteriography, the second is re- by the addition of all the feedback relation- vascularization surgery, and the third is the ships which can be postulated. For example, development of techniques whereby the vasoactive substances may reduce coronary heart rate can be artificially controlled. vascular resistance and hence tend to correct Medical historians may well look back on this the situation that produced the ischaemia. On Br Heart J: first published as 10.1136/hrt.33.2.173 on 1 March 1971. Downloaded from Pathophysiology of coronary circulation 175 Aortic LV ~~~~~~~~~~~Coronary LVe Ventricular Vascular Pesr Volume IResistance %. |ISCHAEMIA in | AbnormalityECG AbnormalityMetabolic DysfunctionLV VasoactiveSubstances FIG. 2 Systems diagram of the patho- experiences on exertion. In Fig. 3 the left -physiology of myocardial ischaemia. Repro- ventricular end-diastolic pressure is seen to duced by permission of Excerpta Medica rise before the onset of chest pain. The Foundation. pressure rise is associated with the appearance of a large 'a' wave. The chest pain dis- the other hand, deterioration of left ventricu- appeared after the administration of nitro- lar function results in an increase in ventricu- glycerin and the left ventricular pressure lar volume and wall tension, which leads to returned to normal.

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