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HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



(and at times chronic) preparations can be made by 

 the intracoronary artery injection of lvcopodium 

 spores (392) or plastic microspheres (2, 34). More 

 gradual constriction of the lumen, however, may 

 reduce the incidence of ventricular fibrillation, 

 minimize infarction, and augment collateral develop- 

 ment. The introduction of intracoronary clots, the 

 induction of coronary thrombosis by electrical means 

 (194, 327), the application to the artery of adjustable 

 Goldblatt clamps, irritant rings or bands of cellophane 

 or bakelite, osmotic clamps, or swelling casein rings, 

 can all ultimately lead to complete coronary artery 

 occlusion (123, 362, 375). Unfortunately, by none of 

 these methods can the time of complete occlusion be 

 known in vivo, nor could the per cent reduction in 

 flow be predicted even if the extent of local reduction 

 in vessel lumen were known. As in other vessels, the 

 effectiveness of a given localized constriction in 

 reducing flow may be large or small and will vary in 

 inverse relation to the peripheral resistance of the 

 vascular bed and lumen of the constricted segment, 

 and in direct relation to the flow velocity, blood 

 viscosity, and axial length of the constricted area 



(153)- 



The hearts of persons afflicted with the clinical 

 signs and symptoms of coronary artery disease, or of 

 animals in which coronary insufficiency has been 

 experimentally induced, generally present a dual 

 problem. The area of the heart with a normally 

 functioning coronary arterial system carries much, 

 if not most, of the burden of metabolism and work of 

 the poorly nourished myocardium, in addition to its 

 own. If the handicapped area of myocardium is 

 large, then the normal portion of the myocardium is 

 heavily loaded and stressed in its efforts to carry the 

 total performance of the heart. In the remaining area 

 of the myocardium, i.e., that handicapped by 

 sclerosed vessels, or vessels not carrying a normal 

 supply of oxygen to the myocardium, the supply of 

 blood and oxygen is too small. 



Natural Responses oj the Normal but Overstressed 

 Portion of the Myocardium 



If the ligation or constriction of a coronary artery 

 is severe enough, useful function is lost within 1 min 

 in the myocardium fed by it, since the muscle mass 

 which was shortening during systole now bulges and 

 lengthens (359). The fact that the area lengthens 

 rather than shortens during systole does not mean 

 that the area is not viable, but rather that although 

 attempting to shorten, the force it exerts is so weak as 



to be overbalanced by the intraventricular pressure 

 which distends it. Since, as will be discussed later, 

 the collateral flow does not increase for some hours, 

 any early natural cardiac compensation must occur, 

 not by improvement of the circulation in the affected 

 area, but through enhanced action of the normal 

 myocardium which is not involved. Loss of contract- 

 ing blocks of muscle following coronary artery 

 occlusion not only reduces the total myocardial force 

 available for raising intraventricular tension, but 

 some of this pressure is spent in stretching the ischemia 

 area and thus is lost for expelling blood into the aorta. 

 The immediate consequences of this, producing a 

 hypodynamic ventricle, are a reduction in left 

 ventricular systolic pressure, aortic pulse pressure, 

 systolic and diastolic pressures, duration of systole, 

 and, especially, stroke volume and stroke work. In 

 this situation, left coronary inflow decreases con- 

 siderably (120, 385). However, within a few minutes, 

 the normal portion of the heart may put into opera- 

 tion compensatory mechanisms by means of which 

 dynamic conditions are largely restored to normal, 

 provided the normal myocardium is in a good 

 responsive condition. In this situation of increased 

 cardiac work per unit of functioning myocardium, 

 coronary flow, arteriovenous oxygen difference, and 

 metabolism of the left ventricle increase. The increase 

 in oxygen uptake is equal to, and at times can be 

 much more than, that lost by the deletion of non- 

 contractile muscle. 



However, not all hearts react as well because the 

 viable portion of the myocardium may not initially 

 respond to stretch, or the same lack of response may 

 occur later after an initial salutary response. This has 

 been especially studied in dog hearts in which inter- 

 ference with the coronary circulation has been by 

 coronary ligature, or by intracoronary injection of 

 plastic microspheres (2, 33). This leads to acute or 

 progressive heart failure associated with profound 

 hypotension, decreased cardiac output and stroke 

 volume, and the clinical signs and symptoms of a 

 shock-like state similar to that which occurs following 

 the loss of blood or plasma. The clinical inference 

 that this is due to supervention of local coronary 

 spasm or peripheral circulatory failure has not 

 received experimental support. Most evidence indi- 

 cates that no primary insufficiency of tfie resistance or 

 capacity vessels exists, nor even any noxious reflex to 

 which the cause of shock could be attributed, nor does 

 such shock arise, apparently, from reflex coronary 

 constriction in the nonoccluded coronary artery (57, 

 153, 233, 254). The experiments of Kuhn et at. (219) 



