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HANDBOOK OF PHYSIOIcx.Y 



CIRCULATION II 



nary flow pattern is similar to the sustained effect 

 obtained during stimulation of cardiac accelerator 

 nerves, i.e., an increased blood flow throughout the 

 cycle (fig. 10). In all animal preparations, as well as 

 in man, myocardial contractility is increased to a 

 marked degree as indicated by the intensity of fibril- 

 latory movements in the fibrillating heart, by de- 

 pression of the isometric and systolic portions of the 

 phasic inflow curve in the dog, and by an increase in 

 myocardial contractile force as measured by a strain 

 gauge arch in man and animal (131). Both intra- 

 venous and intracoronary artery injections increase 

 cardiac oxygen consumption, in the first instance by 

 increasing coronary flow and decreasing coronary 

 A-V oxygen difference (112), in the second instance 

 by increasing coronary flow and increasing coronary 

 A-V oxygen difference (27). This occurs even in the 

 vagus-stopped heart (249). With very small doses, 

 coronary inflow may increase without any change in 

 blood pressure or heart rate and with increased coro- 

 nary A-V oxygen difference. With larger doses, as 

 the systemic effects of the substance (increased aortic 

 blood pressure, cardiac output, and changing heart 

 rate) become evident, the coronary and metabolic 

 effects are exaggerated (90). 



From the preceding it can be seen that there is 

 general agreement that these substances produce 

 coronary vasodilatation. The flow increase is the net 

 result of an augmented extravascular support tending 

 to decrease coronary flow, a metabolic dilator effect 

 tending to increase coronary flow and any direct 

 effect the compounds may have on the coronary 

 vessels. There is, however, disagreement and con- 

 fusion regarding the respective magnitude of each 

 separate effect. There is little doubt that with the 

 larger doses, most of the flow increase is due to the 

 large increase in myocardial metabolism. However, 

 one point of view has it that these substances are 

 primarily coronary vasoconstrictors, their vasodilator 

 action arising secondarily from a hypoxic state of the 

 myocardium as a result of their stimulating effect on 

 the myocardial metabolism. The evidence for this is 

 that epinephrine causes an initial and transient de- 

 crease in coronary flow in the fibrillating heart and 

 in the beating heart (as does cardiac sympathetic 

 nerve stimulation). Elevation of extravascular support 

 as a cause of the early impediment to flow here ap- 

 parently does not occur since intramyocardial pres- 

 sure does not rise in the fibrillating heart (27), and 

 extravascular resistance falls somewhat in the vagus- 

 stopped heart (236). Unfortunately, since the duration 

 of the period of constriction is so fleeting and the flow 

 effect so mild, the view is very difficult to document. 



acetylcholine. Acetylcholine, intra-arterially, in- 

 creases coronary blood flow in the dog in the fibril- 

 lating heart and in the heart-lung preparation (10). 

 In the open-chest dog, intravenous injection of acetyl- 

 choline decreases aortic pressure and coronary flow, 

 and increases heart rate as a result of a decreased 

 systemic peripheral resistance (339). Intracoronary 

 artery injection of effective doses of this hormone, and 

 also intravenous injection (provided the blood pres- 

 sure is mechanically compensated by an aortic clamp 

 and the heart electrically driven following surgical 

 induction of an A-V heart block), increases consider- 

 ably left coronary inflow and coronary sinus flow, 

 and decreases the left ventricular function curve (90, 

 339, 405). If the intracoronary dose is properly chosen, 

 this response occurs without a significant effect on the 

 systolic blood pressure, heart rate, systolic 'diastolic 

 time interval, cardiac output, cardiac work, but the 

 myocardial oxygen consumption per minute and per 

 heart beat increases. The increased coronary flow is 

 completely abolished by atropine (405). Since the 

 mechanical and metabolic factors which could in- 

 fluence coronary flow are thus excluded, the increase 

 in coronary flow represents a true coronary vasodila- 

 tation (see fig. 13). The relation between myocardial 

 oxygen consumption and left ventricular work is not 

 changed. Consequently, the induced depression of 

 myocardial contractility or work per unit of filling 

 pressure is not associated with any change in myo- 

 cardial efficiency (work per unit of oxygen consump- 

 tion). 



thyroid. The myocardium participates in the in- 

 crease in oxygen consumption characteristic of all 

 body tissues in thyrotoxicosis (398). This hyper- 

 metabolism is accompanied by an increase in coronary 

 blood flow, a decrease in coronary vascular resistance, 

 and an increase in oxygen consumption per minute 

 and per beat. Since there is an increase in oxygen 

 usage per beat, cardiac oxygen utilization is pre- 

 sumably related not only to the increase in heart 

 rate but to the general hypermetabolism of the myo- 

 cardium as well (230, 317). 



Hypothyroidism in man has been shown to be 

 associated with a reduction in heart rate, cardiac 

 output, arterial blood pressure, and body oxygen 

 usage. In vitro studies of experimentally induced 

 hypothyroidism have demonstrated a reduction in 

 oxygen consumption of the myocardium (130). Con- 

 trolled experimental inactivation of the thyroid by- 

 use of I 131 in the dog leads to standardized changes in 

 the systemic circulation (342). In addition, coronary 

 sinus flow (N 2 method) and left ventricular oxygen 



