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Quinidine syncope is an unpredictable side effect of quinidine administrateion which has a mortality rate of 11.5 per cent when managed with conventional drugs and direct-current countershock. In 2 patients with quindine syncope, the arrhythmias were effectively controlled within 30 minutes following the slow infusion of 150 mg. of bretylium tosylate. This control is contrasted with 2 cases managed in the conventional manner. Bretylium tosylate is a quaternary amine with unique antifibrillatory properties and appears to have a significant role in the management of these arrhylmias.

Combining propranolol and quinidine should improve the antiarrhythmic action of quinidine by blocking beta adrenergic receptors, an action helpful in cases of arrhythmias associated with anesthetic agents, digitalis and stress. To test this hypothesis, 60 patients with paroxysmal arrhythmias resistant to quinidine and 17 with chronic atrial fibrillation were given propranolol alone or in combination with quinidine (or procainamide) and followed up 1 to 17 months. Patients with severe aortic valve disease, severe mitral insufficiency, acute myocardial infarction or obstructive airway diseases were excluded from this study. The condition of 13 of 19 patients with paroxysmal atrial or nodal tachycardia was improved. In paroxysmal ventricular tachycardia combined therapy or propranolol alone was effective in 11 of 14 patients. Paroxysmal atrial flutter or fibrillation was suppressed in 11 of 16 patients, with a 75 percent or greater reduction in attacks. Prophylaxis of chronic atrial fibrillation terminated by drugs or by electroshock was effective in 9 of 11 patients (15 trials) followed up for 7 months. Sustained atrial fibrillation was terminated with propranolol, 40 to 160 mg, and quinidine sulfate, 1.2 to 1.6 g/day, in 41 percent of patients, a result no better than with propranolol alone. Propranolol slowed the ventricular rate in normal sinus rhythm as well as in atrial fibrillation and flutter. Significant slowing, although it was less in magnitude, occurred with the combination of propranolol and quinidine. It is concluded that propranolol potentiates quinidine and allows effective prophylaxis of atrial, nodal and ventricular arrhythmias in quinidine-resistant patients. Diarrhea was the only side effect peculiar to the combination of drugs.

Digitalis accelerated the rate in atrial flutter resulting in atrial fibrillation, whereas the addition of quinidine slowed the atrial rate producing either asystole or interference dissociation. In some patients receiving both digitalis and quinidine, the atrial rate showed less of a tendency to slow or actually increased, resulting in atrial fibrillation followed by normal sinus rhythm. This suggests an overriding effect of digitalis. Since the spontaneous termination of atrial flutter occurred in unknown circumstances that usually slowed the atrial rate and asystole was observed, this suggests that asystole is not a toxic effect of quinidine. Atrial flutter, fibrillation, and atrial premature beats began more commonly in the P-T cycle than in the T-P cycle. Since atrial recovery is more likely incomplete during the P-T cycle, this favors reentry as the underlying mechanism in the patient studied. Atrial and nodal tachycardia begin with an irregular sequence of premature beats before a stable tachycardia is established. There is usually a significant slowing of the rate prior to termination of the abnormal rhythm. Sinus arrest with ventricular escape is the usual method of termination, regardless of the form of therapy used. Bursts of rapid ventricular rhythm resembling ventricular tachycardia were seen only after the use of pressor agents. Atrial tachycardia with block treated with digitalis shows an initial atrial slowing but, as the dose of digitalis was raised in one patient, abrupt increases in atrial rate occurred until the rhythm terminated. This is a mechanism similar to that seen in the digitalis-induced termination of atrial flutter.

The effective refractory period was determined at the surface and in the deeper layers of the dog heart and was correlated with the surface T-waves. A small delay in recovery of cardiac excitability appeared at the surface when T-waves were negative and in the deeper layers when T-waves were positive. Acute injury produced by ligation of the coronary artery caused a marked acceleration of recovery in the deeper layers, sometimes extending to the surface.

Study of the cardiovascular effects of glucagon in man have shown a positive inotropic and chronotropic effect resulting in an increase in cardiac output.1-3 These effects occur one to 3 minutes after the intravenous injection of 3 to 5 mg. of glucagon and are dissipated in 30 minutes. These effects are similar to those of isoproterenol; however, glucagon has a limited chronotropic effect in man’ and has not caused arrhythmias even in the presence of digitalis.2 In contrast, a recent study of patients with chronic valvufar heart disease concluded that these cardiac effects were variable, not dose-related, and of small magnitude when present.4 In addition to these cardiac effects, glucagon has been shown to increase renal excretion of water and electrolytes.6 Since previous studies are limited to the observation of the effects of a single bolus injection, given to patients who were not in stress situations, it seemed appropriate to study the feasibility and efficacy of a continuous infusion of glucagon over a period of days in the treatment of conditions with low cardiac output or cardiogenic shock. Methods

The evidence has been reviewed which suggests that the upstroke of the action potential in heart muscle is due to the entry of sodium ions. This conclusion is based on the failure of the upstroke to occur if 90 per cent of the sodium is replaced by sucrose, and the demonstration of a reduction in amplitude of the rising phase of the action potential with each decrement in extracellular sodium concentration or an increase in amplitude with increasing extracellular sodium concentration. In addition, the demonstration of a change in membrane resistance of one-hundred-fold at the time of the rising phase suggests increased permeability of the membrane at this time. The voltage-clamp studies in the squid giant axon clearly show an inward movement of current during the rising phase, which disappears when choline replaces sodium in the perfusing bath. The resting membrane potential resembles the model of a potassium and chloride concentration cell, since calculations based on measured concentrations across the membrane agree fairly closely with measured potentials. Furthermore, the membrane resting potential is altered in a predictable manner by changed extracellular potassium and chloride concentration, but is not appreciably affected by changing sodium concentration. Since the skeletal muscle membrane appears to be freely permeable to chloride, and only sparingly so to potassium, and since potassium permeability is selectively altered during the electrical cycle, the chloride ionic concentration gradient is probably dependent on the transmembrane potential, and, therefore, is passive. The current carried by the chloride ion in cardiac fibers is small. Little is known of the factors which alter membrane permeability or affect the transfer rates during recovery, but it is apparent that sodium is removed from the cell after the rising phase and is replaced by potassium to restore membrane resting potential.

The acceptable zeros of the potential of the electrical fields produced by certain dipole distributions in homogeneous volume conductors is discussed. A bridge circuit is described by which a solution of the three-arm and the four-arm central terminals of Wilson may be solved for a zero of potential of the field produced by an arbitrary distribution of dipoles in a homogeneous volume conductor. An acceptable zero of potential for evaluation of the potentials in a locus on the "body" surface distant from the heart is described.

Expanding the frequency response of the electrocardiogram and its derivative to 1,000 cps revealed notching in certain parts of the QRS complex which correlates with the presence of primary myocardial disease. Chi-square analysis of data from 169 patients with myocardial involvement indicated that notching on the downstroke of leads X, V 4 , and V 6 separated abnormal from normal patients at the 1% level of significance, whereas fine and coarse slurring showed reverse correlation at the 1% level of significance. This suggests that notching and not slurring is the important evidence of disease. Neither notching nor slurring was significant at the peak of the R wave in any lead. Study of individual cases revealed that complete right and left bundle-branch blocks do not mask high-frequency components caused by myocardial disease nor do they produce high-frequency components. Conclusions regarding specific diagnostic nostic criteria, however, should serve only as guidelines.

Accelerated recovery, as manifested by shortening of the effective refractory period after coronary artery ligation, occurred at either the epicardial or endocardial surface or both in 11 of 13 animals tested with a mean shortening of 15.7 per cent at the epicardial and 13 per cent at the endocardial levels. These changes are attributed to severe anoxia and are believed to be limited to the ischemic area, since studies in the periphery of an infarcted zone show no significant changes in the first 3 hours. In one instance a minor acceleration of recovery was found after 3 hours at the endocardium. All studies showed a final period of delayed recovery. It is felt that this probably reflects a prolonged duration of the membrane action potential during the later stages of myocardial infarction. This is supported by both experimental and human electrocardiographic data which show prolongation of the Q-T interval in association with deeply inverted T waves following the period of acute injury. Transmural temperature studies after coronary artery ligation showed a prompt fall in 2 studies out of 7 and no acute change in the others. Irrigating the pericardial sac with warm Ringer's solution reversed the pre-existing transmural temperature gradient, caused the T waves in epicardial leads to change from negative to positive, and reduced the duration of the effective refractory period at both the endocardial and epicardial surfaces, especially the latter. During the time that the T waves were upright, recovery was completed earlier at the epicardial than at the endocardial surface.

Propagated wavefronts were produced by mechanical stimulation at points located deeply within the myocardium, and the external field so produced was measured by electrodes located within a radius of 10 mm. from the centrally stimulated point. In 104 experiments in 10 dogs the external field so produced was negligible until propagation reached either the epicardial or endocardial surfaces. If it is assumed that propagated intramural activity is temporarily a closed electromotive surface, then the data presented suggest that there is a uniform difference in potential across this surface. Since there is no fundamental difference in the wavefront characteristics of closed electromotive surfaces and those which present boundaries on the epicardial or endocardial surfaces, these data strongly suggest that there is a uniform difference in potential across all propagated wavefronts in normal ventricular muscle.

The transmyocardial temperature gradient was measured in both right and left ventricles and in the septum of the dog by percutaneous ventricular puncture, using a no. 21 thin-wall needle fitted with a thermocouple stylus. The outer half of the left ventricular myocardium was invariably warmer than the endocardium. The peak temperature of the right ventricle was located midway between the endocardium and epicardium. The midseptal region was found to have a higher temperature than either its right or left endocardial aspects. The left ventricular cavity was cooler than the right ventricular cavity by a mean of 0.1°C. The transmyocardial temperature gradient was measured successfully in the left ventricle of two patients with cardiac disease. As in the dog, the outer layers of the myocardium were warmer than either the endocardium or cavity in these two patients. In one patient the T waves in the left precordial leads were negative and in the other the T waves were upright in the same lead. The location of peak temperature consistently in the outer half of the left ventricular wall may partly explain the normal upright T wave and may contribute to a more rapid recovery in the outer layers of the ventricle compared with the inner layers. However, reversal of the T wave must be explained by other factors and it is apparent that the polarity of the T wave is not governed exclusively by the transmyocardial temperature gradient. The transmyocardial temperature gradient may be explained partly on the basis of differences in heat removal by blood flow in the coronary system as well as in the ventricular cavity. The latter was found to be an important factor, because during ventricular fibrillation the transmyocardial temperature gradient was abolished.

After a brief discussion of the lead field concept and an illustration of its application using a Teledeltos paper model, studies carried out on patients, employing multiple electrode or grid arrangements located over the precordium and the left posterior chest, to obtain the sagittal component of cardiac electromotive forces (e.m.f.'s), are described. On the basis of these observations, a minimum of 15 properly arranged and connected electrodes should be employed in the anterior electrode system but fewer will be needed posteriorly. A scheme, using 63 electrodes mounted in sponge rubber, has been devised to simplify the grid arrangement.

Antazoline is a comparatively safe and effective antiarrhythmic drug in many situations, for both the conversion and prevention of arrhythmias. It appeared to be most effective in the abolition of ventricular tachycardia, possibly helpful in 2 cases of cardiac arrest due to ventricular fibrillation and beneficial in the prevention of atrial and ventricular premature beats. It was useful and deserves further trial in the prevention of paroxysmal ventricular tachycardia. It was almost ineffective in the conversion and prophylaxis of atrial flutter and atrial fibrillation but appeared to be of value in the prevention of paroxysmal atrial tachycardia. There was a high incidence of mild side effects, mostly of the gastrointestinal type, some of which were prevented by taking the drug with meals or with an antacid preparation. No irreversible or serious side actions were encountered, but diarrhea, central nervous system symptoms and chills and fever necessitated stopping the drug in a small percentage of patients.

he occurrence of paroxysmal ventricular tachycardia during the surgical management of valvular heart disease carries an unfavT orable prognosis because of the risk of ventricular fibrillation and death. The prevention and treatment of ventricular tachycardia with cardiac depressant drugs have not been consistently successful, and use of such drugs is not desirable during the immediate postoperative period. This paper describes four patients in whom recurrent episodes of ventricular tachycardia were successfully controlled by temporary cardiac pacemaker. A 47-year-old woman was admitted in January, 1967, because of severe dyspnea. She had had rheumatic fever at age 16 but had remained asymptomatic subsequently until eight years previously, when she had developed dyspnea on exertion and pedal edema. During the two years prior to admission she had noted progressive orthopnea, paroxysmal nocturnal dyspnea, and edema. Physical examination and diagnostic studies including cardiac catheterization and cineangiocardiography showed mitral stenosis, mitral insufficiency, aortic stenosis, aortic insufficiency, tricuspid insufficiency, pulmonary hypertension, and congestive heart failure. Digoxin was not administered during the 48 hours before operation, and diuretics were stopped five days before operation. The total body potassium determined with radioactive potassium was low. The serum potassium was 3.1 mEq. per liter. Using extracorporeal circulation, the mitral and aortic valves were replaced with Starr-Edwards valves and a tricuspid valvuloplasty was performed. A temporary pacemaker wire was left in the right ventricle as a prophylactic measure. A tracheostomy was carried out. The patient tolerated the operation well. She was placed on assisted ventilation. Following operation she began to develop short runs of ventricular tachycardia with an irregular ventricular rhythm between episodes. The heart was paced at a rate of 85 beats per minute, and no further episodes of ventricular tachycardia occurred. The morning following operation the pacemaker was turned off, and again Case 1.

The temperature difference (Tg) across the wall of the left ventricle has been studied in the dog by percutaneous left ventricular puncture. The temperature is higher in the epicardial layer than in the endocardial layer. A difference ranging from 0.20 to 0.70 C was found in all experiments. The TG was found to be stable over a long period of time and was not altered by infusion of isoproterenol or norepinephrine despite significant hemodynamic changes. On the other hand, the TG was reduced markedly when acute anemia or hypoxia was induced. The results with hyperoxia were inconsistent, although the TG was increased in half of the dogs studied. The magnitude of the TG is probably due to the effects and counteractions of many factors. These may include uneven heat production in different layers of the heart, insulation of the pericardium and chest wall, and rate of heat removal by the coronary blood flow and by left ventricular cavitary blood flow. In these experiments the fall in TG associated with anemia and hypoxia is assumed to be due to increased heat removal by the disproportionately increased coronary blood flow. anemia; hypoxia; coronary blood flow; left ventricular heat production; left ventricular puncture Submitted on August 3, 1964

The closest analog to propagated excitation of the heart is an electromotive surface. The width of the cardiac electromotive surface was 0.9 ± 0.1 mm and was remarkably constant. The mean epicardial surface component of voltage across the electromotive surface was 62.4 ± 7.2 mv with the chest closed and 74.1 ± 8.3 mv with the chest open. This 18.7% increase is significant ( P < .001) and suggests a shunting effect of the lungs and thorax. Fortuitous measurement of voltage across the electromotive surface yielded nine values in excess of 80 mv and two above 90 mv, suggesting that the true voltage across the electromotive surface is of about the same magnitude as the transmembrane action potential. Cross-fiber activation resulted in a 29.5% reduction in voltage, a 51.8% reduction in conduction velocity and notched QRS complexes. A closed electromotive surface has no external electrical field, suggesting that its voltage is uniform. The voltage between two electrodes, both in advance or toward the rear of a normally propagated open electromotive surface, is caused by an extracardiac current path, since removal of the lung from the epicardial surface greatly reduces this voltage and augments that across the electromotive surface.

The histopathology of the sinus node, the atrioventricular node, and the atrioventricular bundle of the heart from a child dying of diphtheria is presented. The terminal illness included atrial arrhythmias and heart block. [see figure in the PDF file] [see figure in the PDF file] The possible importance of the neuropathology of the diphtheritic heart is indicated.