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HANDBOOK OF PHYSIOLOGY -^ CIRCULATION I 



not change for minutes, as in breathing CO 2 at even 

 extremely liigh concentrations. The combination of 

 hypoxia and hypercapnia, liovvever, leads to severe 

 cardiac failure in a relatively short time. If the CO2 

 content of the perfusing fluid of an isolated cat's 

 heart is increased, the T wave is heightened, even if 

 the electrolyte composition of the fluid is kept con- 

 stant. A reduction of coronary flow influences T in the 

 same direction (493). Oxygen lack (by breathing air 

 with low o.xygen tension or by breathing at high alti- 

 tudes) has been introduced into clinical diagnosis by 

 Levy. It primarily influences T, and in cases where a 

 latent coronary insufficiency is present, the vector of 

 the ventricular gradient shifts into abnormal positions 

 (i 10). In the normal heart under severe oxygen lack, 

 T is flattened or even (in complete anoxia) inverted, 

 and the ST segment is slightly depressed in some cases; 

 but it has been found that hyperventilation and the 

 loss of CO 2 may be responsible to a degree for such 

 effects, which disappear after adding CO 2 to the in- 

 spired air. This fact indicates the necessary conclusion 

 that all influences of hypoxia are complicated : a direct 

 metabolic impairment is overlaid with a secondary 

 alkalosis, if respiration is increased. The central action, 

 developing in three phases, brings an additional 

 factor into play. In phase I of the central action, the 

 heart rate is increased by increased sympathetic tone. 

 The second phase is characterized by a sudden drop 

 in heart rate, which is centrally induced as well, Ijut 

 by a prevailing vagal activation. Phase III is charac- 

 terized by severe cardiac disturbances, as impaired 

 propagation, ectopic rhythms, etc. Phase II and III 

 are never realized under clinical test conditions. They 

 may, however, occur spontaneously at altitudes near 

 5000 m. The PQ time and the QRS duration are 

 shortened, due to a fast heart rate. These effects are 

 the simple consequence of augmented central sympa- 

 thetic tone. 



Tlieoretical explanation of anoxic effects meets 

 with considerable difficulties. We know little, at pres- 

 ent, about how the ST and T changes are conditioned. 

 It is obvious that the effects must be due to changes 

 of the monophasic action potentials. The flattening of 

 T could be due to a decrease in the inhomogeneities 

 of repolarization. The action potential is shortened, 

 the plateau definitely flattened under hypoxemia (70), 

 both of which support our assumption, because flat- 

 tening of the plateau indicates diminution of inhomo- 

 geneous repolarization. The ST depression, however, 

 cannot be explained so simply. The ciuestion is 

 whether ST and T changes are due at all to myo- 

 cardial hypoxia. In experiments with dogs, ST and T 



changes did not occur unless the myocardial oxygen 

 tension, measured polarographically, was considera- 

 bly reduced (403, 539) and an ST depression was not 

 found after an application of ergot alkaloids. At the 

 beginning of such experiments in man the .ST depres- 

 sion is maximal, but is apparently conditioned, to a 

 degree, by psychical processes. We therefore may 

 argue the ST and T displacements to be the conse- 

 quence of a local action of adrenaline, which is well 

 known to augment all metabolic processes in the 

 heart, and thereby influence the action potentials. 

 Oxygen lack induces this adrenergic effect centrally 

 and is supplemented in this action by other centrally 

 activating factors. Peripheral oxygen lack fosters this 

 adrenergic effect. If coronary flow is insufficient, these 

 factors are strengthened so that they bring about a 

 severe change of .ST and T under conditions which 

 would not normally lead to marked electrocardio- 

 graphic changes. [For detail see (58, p. 242).] Anoxic 

 effects therefore may be due to two completely dif- 

 ferent mechanisms : one central, acting through the 

 sympathetic innervation; one peripheral, acting 

 through impairment of metabolism. Both mechanisms 

 will be discussed in the following pages. 



Influence of Autonomic Innervation on the ECG 



We here refer only to some questions of interest in 

 clinical application of our problem [for literature see 

 (47, 273, 312, 361)]. There is a very reliable indicator 

 of the autonomic innervation available : the heart 

 rate. Decrease in heart rate indicates an increase in 

 vagal tone, but, unfortunately, neither increases nor 

 decreases in the sympathetic tone are always reflected 

 in the change of rate, because the pacemaker is pre- 

 ponderantly influenced by the vagus. We do know of 

 certain reflex conditions, e.g., the central action of 

 CO 2, where both vagus and sympathetic are acti- 

 vated, as revealed by their augmented action poten- 

 tials, but only the typical vagal bradycardia is effec- 

 tuated. There are still other factors contributing to a 

 degree of uncertainty about autonomic effects on the 

 ECG. First, decisive experiments have been made only 

 with animals, for obvious reasons, but most animals 

 have negative T waves which scarcely can be com- 

 pared with man. If, in an experiment, the autonomic 

 nerves are rcflexly stimulated, the simultaneous activa- 

 tion of both \agal and sympathetic fibers can be 

 scarcely avoided. Pharmacological blocking or stimu- 

 lation are l)y no means as specific as many people seem 

 to believe, and most of the blockers have an action of 

 their own, e.g., as x'asoconstrictors, thus inducing an 



