Kanji Obayashi

The Wolff-Parkinson-White syndrome: Pharmacologic effects of procaine amide☆

The effect of procaine amide, 10 mg. per kilogram via intravenous infusion, was studied in 13 patients with the WPW syndrome. The delta wave was eliminated by procaine amide in 10 and modified in three patients. This effect lasted between 30 minutes and 8 1/2 hours and was unrelated to the total dose administered. Anterograde A-V conduction was assessed by atrial pacing with increasing rates. More rapid atrial pacing rates with 1:1 A-V conduction were observed in patients who maintained rather than lost their delta wave during pacing. Ventriculoatrial conduction was assessed with ventricular pacing at increasing rates; ventricular conduction time was fixed regardless on the pacing rate. Procaine amide significantly prolonged V-A conduction time in six and blocked V-A conduction in one patient. In addition, A-V and V-A refractory periods were measured by the extrastimulus technique. Two types of responses were observed: (1) Type I or (2) line of identity. A-V nodal refractoriness was observed to be within the normal range. Procaine amide converted anterograde line of identity responses to Type I responses in all patients who had their delta waves eliminated. In this patient group, bypass refractoriness was shorter than A-V nodal refractoriness. Procaine amide was not observed to alter significantly normal A-V conduction as assessed by atrial pacing or A-V refractory period measurements. Furthermore, a significant disparity between the effects of procaine amide on anterograde and retrograde bypass refractoriness was observed. Tachycardias could be induced in nine of the 13 patients with a mean rate of 167.2 +/- 7.9 beats per minute; delta waves were abent during all episodes of tachycardia. Procaine amide prevented tachycardia induction in six of the none patients. Procaine amide therefore demonstrates electrophysiologic effects which would be beneficial for prevention or treatment of reciprocating tachycardias in the WPW syndrome. Moreover, procaine amide would be an ideal agent for the prevention of rapid ventricular rates in patients with the WPW syndrome and atrial fibrillation.

Cardiovascular effects of ajmaline

Ajmaline, a rauwolfia derivative, has been found to possess potent antiarrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Hemodynamic studies performed in anesthetized and conscious dogs demonstrated no significant changes in measured hemodynamic parameters at doses equal to or less than 2 mg. per kilogram. Studies in isolated papillary muscle demonstrated no negative inotropic effects until concentrations of 1 X 10(-4). Disparate results were obtained with regard to heart rate reflecting the state of autonomic tone. Electrophysiologic studies in both anesthetized and conscious dogs demonstrated a significant depression of intraventricular conduction with no significant effect on AV nodal conduction; ventricular automaticity was not affected. Ajmaline did not alter digitalis-induced AV nodal conduction prolongation. However, ajmaline dramatically altered or abolished ventricular arrhythmias secondary to acute ischemia. In conclusion, these studies demonstrate that ajmaline specifically depresses intraventricular conduction, suggesting that this drug would be particularly effective in the treatment of re-entrant ventricular arrhythmias.

Cardiovascular Effects of Nicotine in the Conscious Dog Modification by Changes in Autonomic Tone

Studies were performed in conscious dogs in which catheters had previously been positioned for long-term use in the right atrium, right ventricle, pulmonary artery and central aorta. Doses of less than 200 μ g of nicotine injected into the right atrium produced no significant hemodynamic effects. A dose of 200 μ g of nicotine produced initial tachycardia, a subsequent hypertensive response and reflex bradycardia. A 400 μ g dose of nicotine produced a triphasic response: (1) a 2 to 4 second sinus arrest, (2) subsequent sinus tachycardia and marked hypertensive response, and (3) reflex bradycardia with persistent increases in right ventricular end-diastolic pressure. Arterial administration of nicotine in similar doses produced only hypertension and reflex bradycardia. No asystole or tachycardia was observed. Pretreatment with atropine eliminated the asystole produced by intravenous administration of nicotine but did not alter the reflex tachycardia occurring after intravenous or intraarterial administration of nicotine. Pretreatment with propranolol did not prolong the asystole occurring after intravenous administration of nicotine and did not diminish the peak increase in heart rate during phase 2. However, the reflex bradycardia was more pronounced after nicotine was given either intravenously or intraarterially. We conclude that, in the conscious dog, nicotine (1) releases acetylcholine in the right atrium, (2) may depress myocardial function, and (3) produces significant hypertension and reflex bradycardia.