BLOOD SUPPLY TO THE HEART 



1^6 



3»3 



cardial contractility and oxygen consumption may be 

 dissociated. Such drugs may be available but more 

 experimental proof is necessary. 



CORONARY ARTERY DISEASE 



The basic pathological lesion in coronary artery 

 disease is the atheroma which eventually leads to 

 narrowing or occlusion of the coronary artery lumen 

 by progressive intimal thickening, intimal ulceration, 

 hemorrhage or superimposed thrombosis. Thrombosis 

 on an arteriosclerotic basis (43%), arteriosclerosis 

 with and without infarction (41%), and intramural 

 hemorrhage (8'c), also presumably on an arterio- 

 sclerotic basis, account for about go per cent of 

 coronary artery lesions (379). Coronary artery 

 narrowing or occlusions are limited to the three 

 main coronary arteries (50 '"< ) and their primary 

 branches (50%), and are almost entirely epicardial 

 (100). The lesions are localized, segmental, and 

 multiple (avg. 2.5/heart), and 70 per cent occur 

 within 3 to 4 cm of the coronary ostia (39, 184). 

 As a result of this occlusive process, the myocardial 

 circulation is reduced to a variable degree, depending 

 upon the nature and extent of the lesion and the 

 extent to which intercoronary artery collateral 

 development takes place. Serious consequences occur 

 when the extent of the former is large or the latter 

 mechanism fails to compensate for the ischemic 

 changes produced by the atherosclerotic process. 

 The following, singly or together, may then take 

 place: angina pectoris, myocardial infarction, 

 mechanical failure, or sudden death. 



Since Heberden's classic description in 1 768 of the 

 syndrome of angina pectoris, much effort by medical 

 investigators has been directed toward this problem. 

 While there are some dissenting voices (297), general 

 consideration indicates that the production of pain 

 arises from stimulation of sensory cardiac nerve 

 endings which, in turn, arises from imbalance in the 

 heart between supply and demand of oxygen. Sensory 

 nerve endings of the heart (and aorta) are present in 

 the myocardium, endocardium, and epicardium, 

 and in the adventitia of the coronary arteries. Their 

 associated neurones converge in the periarterial 

 plexus of the coronary arteries, continue through the 

 superficial and deep cardiac plexuses and course in 

 the middle and inferior cardiac nerves to join the 

 corresponding cervical ganglia of the sympathetic 

 chain. These centrally bound fibers then descend to 

 the upper thoracic ganglia and reach their cells in the 



spinal ganglia by passing through the white rami 

 communicantes into the first thoracic and upper 4 or 

 5 intercostal nerves. They cross to the opposite spino- 

 thalamic tract and course through the brain stem to 

 the thalamus (397, 401). 



From the preceding, it is obvious that pain could 

 be relieved in different ways: by raising the cerebral 

 level or threshold for pain perception, by attenuation 

 of factors in the environment that lead to stimulation 

 of the cardiac pain end organs, by the induction of 

 proper coronary vasodilatation. However, the physio- 

 logical evaluation of angina pectoris, and of the 

 effects of medical and surgical therapy on it, is 

 limited to study of the relief of the angina of effort in 

 cases where attempts are made to delete the sub- 

 jective element of pain, and to the measurement in 

 equivocal cases of the coronary flow response to 

 vasodilator drugs such as nitroglycerin to determine 

 the ability of the coronary bed to dilate on demand. 

 The latter is predicated upon the experimental 

 finding in advanced coronary artery disease of 

 fixation of the coronary flow when challenged by 

 nitroglycerin (44). Whether the ability of a drug to 

 diminish anginal episodes or to improve the electro- 

 cardiographic response in exercise is an objective 

 measure of positive benefit to a stressed myocardium 

 is still debatable. This is so because it is not known 

 to what extent the influence of the physiology of 

 sensation on angina has been removed, and the 

 assumption must necessarily be made that the electro- 

 cardiographic response correctly indicates myocardial 

 hypoxia or ischemia. 



As yet, experimental studies directly attacking the 

 problem of coronary atherosclerosis have not been 

 productive in elucidating the mechanism of or 

 prevention of the lesion. However, the functional 

 consequences and compensatory physiological re- 

 sponses to controlled experimental coronary con- 

 striction and occlusion, or to the loss of functional 

 myocardial areas in acute and chronic animals, have 

 been extensively investigated. 



No standardizable preparation with coronary 

 artery constriction or occlusion similar to that of the 

 human has been worked out for the experimental 

 animal. Naturally occurring or experimentally 

 induced coronary lesions (dog and rabbit) are similar 

 in many respects to the human lesions, but the 

 endothelium remains intact and ulceration and 

 thrombus formation do not occur. For acute or 

 chronic experiments, an artery may be tied off 

 abruptly and completely or partially, by inserting a 

 probe between the artery and suture (98), or acute 



