>53 6 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION II 



tate the pressure developed within the wall of the left 

 ventricle during systole and to use it as a measure of 

 extravascular support. To do this, pressure pulses 

 have been recorded from a myocardially imbedded 

 vessel (or myocardial fluid pocket connected to a 

 recording manometer). However, experimental work 

 indicates that although these pressures may indicate 

 directional changes in extravascular compression, 

 they are, in part, artifactually produced and, hence, 

 do not approximate the correct values for intramural 

 pressure (153). 



A method recently developed has given some in- 

 formation on this point (323). Continuous measure- 

 ments are made in the open-chest dog while the left 

 coronary artery is perfused with blood under a con- 

 stant pressure. First it is done in the beating heart, 

 and then during ventricular asystole induced by 

 vagal stimulation, or by disconnecting an external 

 pacemaker which drives the ventricles (complete 

 atrioventricular heart block having been surgically 

 produced previously). By either means, the mechani- 

 cal effects of ventricular contraction are largely 

 removed. Induction of ventricular asystole by vagal 

 stimulation always increases immediately (within 

 1 sec) left and right coronary inflow. Thus, ventricu- 

 lar contraction acts to impede coronary flow through 

 the ventricular wall. The extent of the rise of flow is 

 taken to represent the magnitude of the mechanical 

 or passive factors limiting coronary flow. The mag- 

 nitude of this mechanical throttling effect on cor- 

 onary flow during systole normally varies from 

 31 to 300 per cent and averages about 50 per 

 cent. The new flow level represents that state of 

 coronary dilatation related to the condition of the 

 intrinsic smooth muscle of the coronary vessels at 

 the prevailing coronary pressure. The relative con- 

 tribution of extravascular and intravascular re- 

 sistance to an increase of coronary flow has been 

 tested under the different conditions of increasing 

 heart rate, decreased arterial blood oxygen satura- 

 tion, aortic constriction, transfusion, and drug injec- 

 tions. In all instances, the major portion of a flow 

 increase is through active dilatation and not through 

 reduction in extravascular resistance. The largest 

 reduction (40 % ) in extravascular resistance is from a 

 decrease in arterial oxygen saturation (155, 236). 



DETERMINANTS OF NORMAL MYOCARDIAL METABOLISM 



The ability of the heart to do work depends basi- 

 cally on its biochemical activity leading to muscular 



contraction. Cardiac muscle has been found to have 

 basic chemical patterns similar to those of other 

 muscle. The catabolism of fat, carbohydrate, and pro- 

 tein produces free energy, about half of which is 

 dissipated as heat and half is captured as phosphate- 

 bond energy which is used for muscle cell work and 

 for various anabolic activities such as synthesis of 

 glycogen, lipids, proteins, and enzymes. These cata- 

 bolic and anabolic reactions proceed simultaneously 

 under the influence of a complex system of enzymes, 

 coenzymes (from the vitamin B complex), and 

 hormones. 



Coronary sinus catheterization studies in man and 

 dog have indicated that the heart is able to choose its 

 fuel from a variety of foodstuffs. These include 

 mainly glucose, lactate, pyruvate, fatty acids (non- 

 esterified) and, to a lesser extent, acetate, ketone 

 bodies, and amino acids. To determine their quanti- 

 tative contribution to the energy production of the 

 heart, i.e., its oxygen consumption, measurements 

 have been made of their cardiac extraction (coronary 

 artery — coronary sinus difference), their total uptake 

 [coronary flow X (coronary artery — coronary sinus 

 difference of substance)], and the myocardial respira- 

 tory quotient (coronary sinus — arterial carbon dioxide 

 difference; coronary artery — coronary sinus oxygen 

 difference). Excellent correlation has been demon- 

 strated between the myocardial respiratory quotient 

 and the myocardial uptake of substance. The extent 

 to which each substrate contributes to the energy 

 requirement of the heart in vivo is influenced by its 

 concentration (above threshold) in arterial blood. In 

 addition, the state of nutrition of the organism mark- 

 edly influences the kind of substrate used for energy 

 production of the heart. Under postprandial condi- 

 tions, or after glucose infusion, myocardial metab- 

 olism is mainly glucose, lactate, and pyruvate, since 

 its respiratory quotient approximates 0.9 with a high 

 extraction of carbohydrate and a negligible uptake of 

 amino acids. Even the substitution of 5 to 10 per cent 

 oxygen for the normal 2 1 per cent in the inspired air 

 does little to change carbohydrate uptake by the 

 normal heart. During overnight fasting, the heart 

 derives much of its energy from fat, as indicated by a 

 myocardial respiratory quotient of 0.80 with a low 

 extraction and uptake of carbohydrate. With pro- 

 longed fasting, the extraction coefficient for carbo- 

 hydrate practically disappears, those for fatty acids 

 and ketones are maximal and the respiratory quotient 

 is 0.70. As regards the uptake of oxygen, the coronary 

 A-V oxygen differences in man vary linearly with the 

 arterial oxygen content through a range from mild 



