TY - JOUR T1 - STUDIES ON THE CARDIODYNAMIC ACTIONS OF DRUGS III. THE MECHANISM OF CARDIAC STIMULATION BY DIGITALIS AND g-STROPHANTHIN JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 251 LP - 269 VL - 30 IS - 3 AU - CARL J. WIGGERS AU - BARBARA STIMSON Y1 - 1927/01/01 UR - http://jpet.aspetjournals.org/content/30/3/251.abstract N2 - The mechanism of ventricular stimulation by digitalis and g-strophanthin was studied by methods described in preceding papers of this series. Records and data are presented and analyzed. They lead to the concluson that digitalis substances exert a direct stimulating effect on ventricular muscle which manifests itself by an increased gradient of pressure development, a higher pressure maximum within the ventricle, a reduction in the period of systolic contraction and, under certain conditions, by a more rapid isometric relaxation. Digitalis substances produce such effects by increasing the velocity of fractionate contractions, by shortening their duration, and by increasing the speed of their relaxations. Increased rate of fractionate summation does not occur, in fact the stimulating influence persists in some cases where the entry of fractionate contraction is retarded as a result of delayed ventricular excitation. This primary action has, however, been overestimated and is demonstrated neither by the larger systolic discharge nor by characteristic effects on the ventricular pressure curve, alone. This primary action of digitalis is supplemented, and in some cases preceded, by the secondary influence of an increase in initial length. This is naturally accompanied by an increase in initial tension but the latter may be reduced by greater speed of isometric relaxation so that initial tension remains unchanged or becomes even less than normal. In either event, such an increase in initial length can account for all the changes in the intraventricular pressure curve, except the tendency of systole to shorten, and of isometric relaxation to occur more rapidly. When the diastolic arterial pressure is not controlled and rises as a result of the drug's action, the increased arterial resistance so occasioned, influences the vigor of the ventricular beat to a very considerable degree. It contributes to the elevation of initial tension and causes a further increase in diastolic length by "back pressure effects." In consequence, it favors a steeper gradient, a higher pressure maximum and a larger systolic discharge. The latter occurs in spite of a further reduction in the phase of ejection and as a result of the increased velocity of ejection. At no stage of digitalis action is systolic discharge reduced or the diastolic size of the ventricles decreased as long as the rate of the heart is kept constant. Such effects are produced only by cardiac acceleration. ER -