Jerome L. Gilbert

Influence of Sympathomimetic Pressor Drugs on Arrhythmias Caused by Multiple Stimuli

A technic of administering successive stimuli to the heart at various ectopic foci was devised. Under normal circumstances the heart had sufficient power of integration to resist disorganization of its action by these multiple stimuli. Methoxamine, mephentermine and metaraminol had less tendency to increase vulnerability to fibrillation than did levarterenol under these conditions of stress. A new compound (Lilly #20522) blocked for a time the arrhythmia-producing action of levarterenol.

The phenomenon of accommodation in the ventricular myocardium

SummaryThe ventricular and auricular myocardium was found to possess an ability to accommodate to applied electrical current pulses.Accommodation to cathodal current flow was observed even when nonpolarizable electrodes were employed and also when tests were made with chronically implanted metal electrodes in intact anesthetized dogs.Accommodation tended to attain its maximum within 40 to 45 msec after the beginning of the conditioning pulse. It reduced the facilitatory action of the conditioning pulse by 50 to 60%.Post-cathodal and post-anodal changes in excitability occurred. They were of 10 to 15 msec duration following a 70 msec conditioning current flow. They were of lesser magnitude then the average residual facilitation remaining just before termination of conditioning stimuli.Evidence that various circumstances can modify the ability of cardiac tissue to accommodate to intrinsic and applied stimuli was discussed. The possible importance of this phenomenon to the maintenance of effective action of the heart under abnormal circumstances was considered.

EFFECTS OF VASOCONSTRICTOR AGENTS ON CARDIAC IRRITABILITY

A study was made of the effects of the vasoconstrictor drugs epinephrine, levarterenol, methoxamine and mephentermine, on excitability, refractory period, rhythmic abnormalities, conduction times and action potential of the heart. The principal observations were as follows: These drugs with the exception of methoxamine, in doses so graded as to maintain blood pressure levels 30 to 50 mm. Hg above control values, induced ectopic pacemaker action, abnormal spontaneous beats, and abnormal and multiple responses to test stimuli. The action of methoxamine on the heart can be said to be depressant in that it prolonged the action potential and the absolute refractory period, raised the threshold to stimulation and slowed A-V conduction significantly. This was not due to reflex vagal action. All four drugs exhibited some degree of tachyphylaxis with respect to blood pressure maintenance and some other actions. Other details of the comparative effects of these drugs are given in the discussion of results obtained.