ON THE ACTION OF SUBSTANCES OF THE DIGITALIS SERIES ON THE CIRCULATION IN MAMMALS.
In summing up the contents of the preceding pages it may be stated that the action of digitalis has been divided into two stages according to the changes evinced by the ventricles under its influence; of these the first is characterized by marked inhibitory action together with modification of the cardiac muscle, while in the second the inhibitory action is less marked and the muscular action becomes the more prominent feature. The inhibitory action is due to direct stimulation by this series of the pneumogastric centrally in the medulla oblongata and peripherally in the heart. The extent to which the inhibitory mechanism is stimulated varies in different animals and with different members of the digitalis series. The muscular action of small quantities betrays itself in a tendency to increase the extent of the contraction, while in some cases the degree of relaxation reached in diastole is also lessened by it. In larger quantities the series increases the irritability of the cardiac muscle very considerably, and the spontaneous rhythm of the ventricles therefore becomes developed. Through the interaction of these two factors in the first stage the rhythm of the whole heart is slowed, the contraction of the ventricle is more complete, and the diastolic relaxation is generally increased, although it may be unchanged or lessened. The systolic pressure is increased and the fall from maximum to minimum pressure is slower than normal owing to the increased completeness and longer duration of systole (Rolleston). The auricles generally contract with less force and may relax more completely than normally. Sometimes, however, their contractions also are more complete than before the injection of the drug. This latter condition generally precedes the diminution of the force of the auricular contraction. This variation of the effects of digitalis in the auricle explains the changes in intra-auricular pressure noted by Kaufmann. The contraction volume of the ventricles is always much increased, and the output per unit of time is generally augmented, and this together with the contraction of the peripheral arterioles causes an increase in the tension in the systemic circulation, an acceleration of the circulation, and possibly a temporary increase in the pressure in the great veins and in the auricle and ventricle in diastole (Kaufmann). The pressure in the pulmonary artery is practically unaffected by some members of the series, while by others it is considerably increased. This difference in the reaction of the pulmonary circulation is due to the varying extent to which these drugs act on the peripheral arteries and not to any difference in their action on the two sides of the heart. If the inhibitory action be very strongly marked the slowing of the heart may be extreme, the ventricles assuming their own spontaneous rhythm and all connection with the auricles being lost. While the contraction volume of the ventricle is still greater than normal, their output per unit of time may become less than normal, the aortic tension therefore fall and the rapidity of the circulation be lessened. The ventricles maintain their association throughout, and probably the rhythm of the two auricles also remains equal. The ventricular rhythm, however, becomes irregular owing to the variation in the duration of the diastolic pause. The auricles may cease altogether in diastole, or may continue to beat with a slower or faster rhythm than the ventricles. During the second stage the rhythm of the heart becomes accelerated owing to the increased irritability of the heart muscle. The ventricle tends to assume a rapid spontaneous rhythm, while the auricular rhythm is also quicker than in the first stage. When these two rhythms interfere by the passage of impulses across the auriculo-ventricular boundary in either direction, irregularity of the heart is produced, generally bearing a distinctly periodic character. The ventricles continue to maintain their common rhythm, while the auricles and ventricles may contract at quite different rates. The two ventricles, however, do not necessarily contract with equal force, and the contractions of one may present periodic variations in strength, while those of the other may be almost perfectly uniform. The contractions of the auricles vary in the same way as regards each other and the ventricles. The inhibitory nerves are no longer able to slow the ventricular rhythm, but may affect the completeness of systole and diastole in the ordinary way. The auricular contractions can still be lessened in force and possibly be abolished by their stimulation, and the impulses passing between the auricle and ventricle may therefore be blocked and regularity of the heart produced by powerful inhibition. The irregularity of the contractions is therefore due indirectly to the increased irritability of the cardiac muscle and the acceleration must be attributed to the same cause. An extreme phase of this stage produced by the interference of the rhythms is a temporary standstill of one of the chambers, generally the auricle. The irregularity leads to a lessened efficiency of the work of the heart. The output varies extremely in successive observations and the contraction volume of every individual beat may differ. The various chambers often show a tendency to dilate during this stage. The blood pressure in the systemic arteries at first remains high, in fact may be higher than in the first stage owing to the increased rapidity of the heart rhythm, but afterwards falls continuously as the periodic variations become shorter in duration. The auricles generally cease contracting before the ventricles, but not invariably. There is no fixed order in the cessation of the ventricles or auricles. Each division comes to a standstill in a position somewhat nearer diastole than systole and then passes into delirium and dilates to the fullest extent.
Pharmacological Laboratory of the University of Michigan.
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Cushny