Leonard S. Gettes

Use of isoproterenol as an aid to electric induction of chronic recurrent ventricular tachycardia

Abstract Initiation of ventricular tachycardia using isoproterenol administration and programmed stimulation of the heart was attempted in 11 patients with recurrent ventricular tachycardia in whom standard stimulation techniques alone failed to induce the tachycardia. Seven patients had nonsustained and four had sustained ventricular tachycardla. In four patients, ventricular tachycardia was induced by exercise; in the remaining seven, tachycardia was not exercise-induced. Before isoproterenol, single and double ventricular premature depolarizations and rapid ventricular pacing failed to induce the tachycardia in all patients. After intravenous administration of small amounts (6 to 16 μg) of isoproterenol, critically timed single and double ventricular premature depolarizations could reproducibly initiate and terminate the tachycardia in six of seven patients with nonsustained ventricular tachycardia and in three of four patients with sustained ventricular tachycardia. Propranolol (0.05 to 0.1 mg/kg body weight) was effective in blocking the arrhythmia-facilitating effect of isoproterenol in four patients and procainamide (10 mg/kg) was effective in three patients. In two patients, neither propranolol nor procainamide was effective. The precise mechanisms underlying the arrhythmogenic effects of isoproterenol in each patient are not obvious. Nonetheless, our results suggest that the administration of isoproterenol is a useful adjunct when attempting to initiate ventricular tachycardia by stimulation techniques. As such, it should be helpful in carrying out studies designed to establish appropriate therapeutic interventions in patients with recurrent ventricular tachycardia.

Propranolol therapy during pregnancy, labor, and delivery: Evidence for transplacental drug transfer and impaired neonatal drug disposition

The administration of 160 mg of propranolol daily during pregnancy, labor, and delivery was associated with profound hypoglycemia and respiratory depression in a newborn infant. The neonates plasma propranolol level rose from 40 ng/ml at the time of birth to 90 ng/ml four hours later. This increase in plasma propranolol concentration might be due to redistribution of the drug in the neonate as well as to different elimination mechanisms than in adults. The elevated propranolol level four hours after delivery was not associated with any signs or symptoms of drug toxicity, but drug effect was apparent on the electrocardiogram. The administration of propranolol during pregnancy in doses capable of producing therapeutic maternal blood levels may be dangerous to the neonate.

Effects of Low and High Concentrations of Potassium on the Simultaneously Recorded Purkinje and Ventricular Action Potentials of the Perfused Pig Moderator Band

The use of the perfused pig moderator band has allowed us to study the rapid simultaneous changes in Purkinje and ventricular action potentials induced by perfusing solutions of high (10 to 12 mM) and low (0.6 to 0.8 mM) K concentrations. High K shortened the plateau more in Purkinje fibers than in ventricular fibers and decreased the difference between the action potential durations of the two fiber types. Low K prolonged the plateau in Purkinje fibers but shortened it in ventricular fibers and increased the difference between the action potential durations. Low K initially hyperpolarized both Purkinje and ventricular fibers. However, the resting potential of the Purkinje fiber subsequently decreased as phase-4 depolarization increased. The decreased maximum repolarization potential associated with low K-induced pacemaker activity was time rather than voltage dependent. When the perfusate was changed from low K to control (K = 4.8 mM), phase-4 depolarization was rapidly suppressed and the action potential of the Purkinje fiber was shortened to less than that produced by high K, and then changes in amplitude of the resting and action potentials occurred. Our observations help to explain some of the effects of low and high K on rhythm and conduction.

Two Mechanisms of Cardiac Arrest Produced by Potassium

Ventricular arrest occurs in isolated heart perfused with potassium-deficient solution when the extracellular potassium concentration is suddenly raised to a physiological concentration. This is known as a paradoxical phenomenon of Zwaardemaker and Libbrecht. Records of electrocardiograms, and ventricular and atrial transmembrane potentials from perfused rabbit hearts before, during and after this type of arrest revealed that its mechanism differs from the mechanism of cardiac arrest produced by an increase of external [K] above physiological concentration. The Zwaardemaker-Libbrecht phenomenon is associated with a striking increase in the velocity of repolarization while the typical effects of high-K concentration on the resting membrane potential and amplitude and upstroke velocity of the action potential are either very slight or absent. Conduction in the atria, ventricles and between the atria and the ventricles apparently is not disturbed during the Zwaardemaker-Libbrecht phenomenon; therefore, we attribute the cardiac arrest to a selective inhibition of the pacemaker activity. This might be due to an inhibition of the diastolic depolarization of the pacemaker fibers. A speculation is made that the type of imbalance between the intra- and extracellular K concentration in the myocardium which causes the Zwaardemaker-Libbrecht effect in the isolated heart could occur in situ and cause sudden death.

Effect of Premature Depolarization on the Duration of Action Potentials in Purkinje and Ventricular Fibers of the Moderator Band of the Pig Heart: ROLE OF PROXIMITY AND THE DURATION OF THE PRECEDING ACTION POTENTIAL

We compared premature and nonpremature action potentials in Purkinje and ventricular fibers from the moderator band of the pig heart to determine if the duration of premature action potentials depended on factors other than preceding cycle length. In Purkinje fibers, the duration of premature action potentials was cycle-length dependent in responses originating more than 100 msec after the preceding repolarization, but the duration of earlier responses was less than the cycle-length−dependent duration. This cycle-length−independent shortening of premature responses increased with greater proximity to the preceding repolarization and increasing duration of the preceding action potential. In ventricular fibers, the duration of premature action potentials was greater than the cycle-length−dependent duration. This cycle-length−independent lengthening increased as the duration of the preceding action potential increased; it also depended on proximity, being greatest when proximity ranged between 26 and 275 msec. The difference between the durations of simultaneously recorded Purkinje and ventricular action potentials decreased as prematurity increased, but the earliest premature Purkinje action potential was consistently shorter than the simultaneously recorded ventricular action potential. Thus, premature stimulation produced different effects in Purkinje and ventricular fibers. However, in both fibers, the deviation of the duration of premature action potentials from the cycle-length-dependent duration was determined, at least in part, by the duration of the preceding action potential and proximity.

Effect of isoproterenol on the abnormal T wave

Abstract The effect of isoproterenol (1 to 9 μg) administered intravenously within 30 to 90 seconds was studied in 106 patients with abnormal negative T waves. T waves remained abnormal in patients with QRS >- 0.10 second and in patients with myocardial infarction or pericarditis. T wave abnormality was reversed in 96 percent of patients with QRS

The electrophysiologic effects of antiarrhythmic drugs

Abstract In this review antiarrhythmic agents are classified into 3 groups: (1) those that remove or prevent the factors responsible for the electrophysiologic abnormality underlying an arrhythmia; (2) those that enhance the effects of acetylcholine either by increasing parasympathetic effects or by decreasing sympathetic effects; and (3) those that directly alter the electrophysiologic properties of cardiac cells. If bretylium and propranolol are excluded from the drugs in group 3, then all of the drugs within this group have in common the ability to suppress diastolic depolarization and to shift the membrane potential during repolarization from which the earliest premature response can originate to a more negative value. By so doing, the rate of depolarization of the earliest premature response may be increased, in spite of a rightward shift of the membrane responsiveness curve. The importance of these effects is discussed in terms of current concepts of the genesis of arrhythmias.

PROPRANOLOL THERAPY DURING PREGNANCY, LABOR, AND DELIVERY: EVIDENCE FOR TRANSPLACENTAL DRUG TRANSFER AND IMPAIRED NEONATAL DRUG DISPOSITION

The administration of 160 mg of propranolol during pregnancy, labor, and delivery was associated with profound hypoglycemia and respiratory depression in a newborn infant. The neonates plasma propranolol level rose from 40 ng/ml at the time of birth to 90 ng/ml four hours later. This increase in plasma propranolol concentration might be due to redistribution of the drug in the neonate as well as to different elimination mechanisms than in adults. The elevated propranolol level four hours after delivery was not associated with any signs or symptoms of drug toxicity, but drug effect was apparent on the electrocardiogram. The administration of propranolol during pregnancy in doses capable of producing therapeutic maternal blood levels may be dangerous to the neonate.