Billy K. Yeh

Inferior Interatrial Pathway in the Dog

In 20 anesthetized dogs, close bipolar electrograms consisting of two deflections were recorded along the ligament of Marshall in the posterior left atrium. At the inferior portion of the ligament the deflections were separated by an interval of 10−15 msec and at the level of the left superior pulmonary vein by an interval of 60 msec or more. Histological and electrophysiological studies indicated that both deflections were associated with striated cardiac muscle; the first deflection was designated as a left atrial muscle potential and the second as a left atrial tract potential. Although the left atrial muscle potential was coincident with the middle portion of the P wave, the left atrial tract potential occurred during some part of the P-R segment. Conduction to the left atrial tract potential was altered, delayed, or completely blocked during retrograde conduction in the atrium, rapid pacing of the atrium (300−500/min), or local cooling at the point where the ligament of Marshall joined the inferior left atrium near the origin of the coronary sinus. Crushing Bachmanns bundle caused delay in conduction to the left atrial muscle but not to the left atrial tract. Left cardiac sympathetic nerve stimulation induced an atrial activation pattern consistent with pacemaker activity in the inferior left atrium, with inversion of the P wave in lead II. Pacing from the edge of the ligament of Marshall in the posterior left atrium produced the same change in P-wave morphology. These data indicate that the left atrial tract represents a terminal, insulated tract which is activated through an inferior interatrial pathway connecting the inferior right and left atria along the coronary sinus. The terminal end of the tract showed no reinsertion into atrial musculature.

Effects of Dopamine and Isoproterenol on Renin Secretion in the Dog

Summary The effects of intra-arterial infusion of dopamine (3 μg/kg/min) and isoproterenol (0.15 μg/kg/min) on renal blood flow (RBF) and renal venous plasma renin activity (RVR) were studied in eight anesthetized dogs, before and after propranolol. Dopamine caused an increase in RBF from 201±21 to 238±39 ml/min (p < .01); and a decrease in RVR from 470±130 to 333±115 ng/100 ml (p > .05). Isoproterenol increased RBF from 202±28 to 214±39 ml/min (p < .05) and augmented RVR from 470±130 to 1192±395 ng/100 ml (p < .01). Propranolol did not alter the effects of dopamine on RBF and RVR, but effectively blocked the isoproterenol-induced vasodilation and renin secretion. This demonstrates the unique action of dopamine on renin secretion. The presently available evidence suggests that there probably are no specific adrenergic receptors directly mediating renin secretion by the kidney.

Functional Transverse Interconnections within the His Bundle and the Bundle Branches

The existence of transverse interconnections within the His bundle and the bundle branches was investigated in excised preparations from dogs and rabbits. The preparations included the His bundle or one of the bundle branches along with portions of the peripheral conduction system. They were superfused with Tyrodes solution, and conventional electrophysiological techniques for extra- and intracellular recordings were employed. The effects of incisions and of intracellular stimulation within the proximal conduction system on distal activation were observed. Transection of 90% of a right bundle branch or intracellular stimulation within that bundle branch did not alter the distal activation pattern observed during surface stimulation of fully recovered fibers. Transection of 90% of the left bundle branch or intracellular stimulation produced a temporal shift of no more than 4 msec in the activation of widely scattered distal sites. Intracellular stimulation in the left bundle branch never produced dispersion of more than 3 msec in distal activation compared with the effects of surface stimulation. Intracellular stimulation at various points within the His bundle always activated the right bundle branch in a manner identical with activation during physiological atrioventricular conduction. Transverse velocity in the conduction system was less than longitudinal velocity. It is concluded that functional transverse interconnections are relatively numerous in the His bundle and the bundle branches.

Sodium nitroprusside as a coronary vasodilator in man. I. Effect of intracoronary sodium nitroprusside on coronary arteries, angina pectoris, and coronary blood flow.

Summary The effect of the intra-arterial injection of 5 to 10 μg of sodium nitroprusside on the caliber of normal and diseased coronary arteries was evaluated in 21 patients during diagnostic cardiac catheterization. In addition, the effect of intragraft injection of 5 μg of the same agent on the blood flow in aorta-right coronary artery saphenous vein bypass grafts was also evaluated intra-operatively in two patients. The compound induced an increase in the caliber of both normal and stenosed coronary arteries as well as an increase of flow in the grafts. Consistent with measurements of coronary flow response to sodium nitroprusside, angina pectoris which developed in four patients during cardiac catheterization was immediately relieved and the ischemic ST-segment depression significantly reversed after injection of 5 to 10 μg of the drug into the left main coronary artery. Within the dose range used, the drug caused no significant effect on systemic blood pressure or apparently deleterious electrophysiologic changes. No side effects were observed. We conclude that the primary direct action of sodium nitroprusside in the human coronary artery is vasodilatory.

Prevention and abolition of ouabain-induced ventricular tachycardia by potassium canrenoate in dogs☆☆☆

It has been shown that spironolactone (Aldactone) protects the rat against myocardial necroses induced by digitoxin (Selye et al., 1969) through the induction of hepatic microsomal enzymes (Solymoss et al., 1969). The present study investigated whether spironolactone (S) and potassium canrenoate (K Can), a newly synthesized specific antagonist of aldosterone, had protective effects against ouabain (OU)-induced ventricular tachycardia (VT) in dogs. After a priming dose of 7.5 μg/kg, OU was infused at a rate of 2 μg/kg i.v. to the following 4 groups of pentobarbital anesthetized dogs until the development of VT: (I) 8 control dogs; (II) 5 dogs pretreated with i.m. S, 5 mg/kg, twice daily for 5 days; (III) 8 dogs receiving a simultaneous infusion of K Can 0.02 mEq/min plus OU; (IV) another 8 dogs receiving a simultaneous potassium chloride (KCl) infusion, also 0.02 mEq/min, plus OU. VT occured at 34±1 min in the control group; 32±1 min in group II, 47±4 min in group III (p<0.02, compared to groups I, II and IV), and 34±2 min in group IV. VT was converted by 0.5 mEq of K Can to sinus rhythm in 6 of 11 dogs; all conversion took place within 1 min after K Can injection. No conversion of VT was noted either after the administration of equivalent amount of S (8 experiments) or KCl (10 experiments). These data indicate that K Can has potent antiarrhythmic activity in OU toxicity. This antiarrhythmic activity of K Can probably was not related to the potassium ion, and was not mediated by a mechanism related to the induction of drug-metabolizing enzymes in the liver.

Potassium Canrenoate in the Treatment of Long-Term Digoxin-Induced Arrhythmias in Conscious Dogs

The effects of potassium canrenoate on arrhythmias induced by long-term progressive digoxin toxicity were studied in eight conscious beagle dogs. Sinus bradycardia and sinoatrial block, as well as atrioventricular (A-V) conduction disturbances, were consistently alleviated by administration of potassium canrenoate. Premature supraventricular (including junctional) and ventricular depolarizations as well as ventricular tachycardias were also suppressed. Although potassium canrenoate always terminated the digitalis-induced arrhythmias, it usually converted the rhythm to sinus arrhythmia rather than to normal sinus rhythm. Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication. These data indicate that canrenoate, a diuretic agent with reported positive inotropic effects, may be useful in the treatment of digitalis-induced arrhythmias in man.

Reversal of Ouabain-Induced Electrophysiological Effects by Potassium Canrenoate in Canine Purkinje Fibers

Canrenoate, an aldosterone antagonist, was administered to normal and ouabaintreated Purkinje fibers excised from the hearts of mongrel dogs and perfused with Tyrodes solution at 35–37°C. Intra- and extracellular potentials were recorded with conventional techniques. Potassium canrenoate in concentrations up to 1 × 10−3M or sodium canrenoate in concentrations up to 5 × 10−3M had inconspicuous electrophysiological effects on untreated Purkinje fibers. The duration of the action potential was slightly shortened. Amplitude of resting and action potentials, rate of rise of action potentials, conduction velocity, membrane responsiveness, automaticity, and excitability were not significantly altered by canrenoate. In contrast, potassium canrenoate in concentrations of 1 × 10−4M to 5 × 10−4M produced rapid restoration toward normal of fibers moderately or severely affected by ouabain (10−7M). Resting and action potentials were augmented, rate of rise of action potentials was increased, excitability was restored, and conduction was enhanced. Also ouabain-induced spontaneous rapid firing could be terminated. Twice equimolar doses of KCI were ineffective. The data suggest that canrenoate might be a specific antagonist to the electrophysiological effects of digitalis.

Mobitz type II A-V block as a manifestation of digitalis toxicity.

Summary A case of Mobitz type II A-V block induced by chronic digoxin toxicity in a conscious dog is reported. This arrhythmia disappeared shortly after the discontinuance of digitalis administration. We believe this is the first experimental evidence that digitalis can cause Mobitz type II block. It is therefore reasonable to suggest that digitalis therapy be temporarily discontinued in digitalized patients showing Mobitz type II block, since digitalis intoxication can manifest as Mobitz type II block.

The specificity of potassium canrenoate, a steroidal antidysrhythmic drug

The antidysrhythmic property of potassium canrenoate [potassium 3‐(3‐oxo‐17β‐hydroxy‐4, 6‐androstadien‐17α‐yl) propanoatel was studied in ventricular dysrhythmias induced by ouabain, norepinephrine, barium, and strontium, as well as ligation of the anterior descending coronary artery in dogs anesthetized with sodium pentobarbital. Potassium canrenoate (KC) (12 mg/kg) was effective in abolishing the ouabain‐induced ventricular bigeminy and ventricular tachycardia without significantly altering the inotropic response of the heart to ouabain. Our previous data indicate that equimolar amounts of potassium chloride were ineffective under the same circumstances. KC (12 mg/kg) had no effect on ventricular dysrhythmias caused by norepinephrine and myocardial infarction. Up to 30 mg/kg KC did not suppress ventricular tachycardia induced by barium or strontium. The canrenoate molecule appears to be a specific antagonist to the electrophysiologic toxicity of cardiac glycosides.

Antiarrhythmic activity of four pteridine compounds in ouabain intoxication.

The antiarrhythmic effects of 4 pteridine analogues, 2 of which are potassium‐sparing diuretics, triamterene (2, 4, 7‐triamino‐6‐phenylpteridine) and [2‐phenyl‐4, 7 diaminopteridine‐6‐(N‐diethylaminoethyl) carboxamide] and 2 of which have no diuretic effects [2‐phenyl‐4, 7‐diaminopteridine‐6‐(N‐2‐hydroxyethyl) carboxamide] and [2‐phenyl‐4, 7 diaminopteridine‐6‐(N‐dimethylaminopropyl) carboxamide], on ouabain‐induced ventricular tachycardia in intact pentobarbital‐anesthetized dogs were investigated. Ouabain was given as a continuous infusion 2 µg/kg/min intravenously until 5 min after the onset of a sustained ventricular tachycardia. It was found that both 6‐(N‐dimethylaminopropyl) and 6‐(N‐diethylaminoethyl) carboxamide derivates of the pteridine had a significant protective effect against ouabain‐induced ventricular tachycardia in dogs that had been pretreated with a dose of 5 mg/kg intravenously. At this dose the 2 pteridine compounds with diuretic activity exhibited a transient antiarrhythmic effect in abolishing the ouabain‐induced ventricular tachycardia while those without diuretic properties failed to suppress the ventricular tachycardia.