On the mechanism of myocardial sensitization to catecholamines by hydrocarbon anesthetics.

During the past decade, considerable progress has been made in our understanding of the mechanism underlying sensitization of the heart to the arrhythmogenic action of the catecholamines by hydrocarbon anesthetics. This review includes the following: a brief discussion on the concepts of the mechanics of induction of cardiac arrhythmia; recent studies on sensitization with special reference to the primary locus of this action and the principal mechanisms involved; and the contribution made by microelectrode studies on various types of cardiac tissue and the importance of cardiodynamic effects. In addition, atrioventricular conduction studies using bundle of His preparations are described. Drug interaction between anesthetic agents, muscle relaxants, and other drugs are discussed. Suggestions for future research and a section of summary and conclusions are included.

Increase in ventricular fibrillation threshold following blockade of atrioventricular conduction.

The threshold for electrically induced ventricular fibrillation was determined in anesthetized open-chest dogs, before and after blockade of atrioventricular (A-V) conduction. Without exception, the threshold was significantly elevated after creation of the block. The precise mechanism of this effect is not known at this time. However, it is apparent that when ventricular fibrillation thresholds are being determined, the functional status of A-V conduction should be established and maintained throughout the study.

Cardiac arrhythmias in sensitized hearts - primary mechanisms involved.

The primary locus of the sensitizing action of hydrocarbon anesthetics to the arrhythmogenic action of catecholamines has now been shown to be the heart itself. It has been demonstrated in the completely isolated heart perfused with an artificial medium. The induction of ventricular arrhythmias, which begins with a shift in the site of the primary pacemaker from the sinus node to the A-V junctional area, requires the development of a significant intraventricular pressure. It is facilitated by a marked reduction in the refractory period of Purkinje fibers with little concomitant effect on regular myocardial fibers.

On the mechanisms of coupling in adrenaline-induced bigeminy in sensitized hearts.

The mechanism of coupling in adrenaline-induced ventricular bigeminy in sensitized hearts has been investigated in intact animals, isolated preparations, and single cardiac fibers. The electrophysiological and cardiovascular dynamic changes during the development of fixed interval coupling strongly indicate that the coupled beats result from stretch of subsidiary pacemaker fibers in the specialized ventricular conduction system, induced by the mechanical response to the normally conducted sinus impulse. The resulting intraventricular pressure elicits an extrasystole when a certain critical end systolic pressure for a particular animal is reached. The interval between the normal and premature ventricular beat decreases progressively as the intraventricular pressure rises, as a result of the combined action of adrenaline and postextrasystolic potentiation. The onset of ventricular bigeminy is preceded by a shift in the pacemaker site to the A-V junctional area, due to a differential effect of the anesthetic-adrenaline combination on fibers of the S-A node and those in the junctional area. The degree of prematurity of the coupled beat shows an inverse linear relationship to the intraventricular pressure of the initiating beat at the end of systole. The premature QRS complex occurs after a period of mechano-electrical latency, the duration of which is directly related to this pressure.

Cardiovascular responses to intraosseous injections containing catecholamines.

The cardiovascular responses to Adrenaline and Noradrenalin, given intraosseously, are reported. Intraosseous injections of anesthetic containing catecholamines clearly demonstrate the rapidity with which the catecholamines are absorbed into the general circulation. Adrenalin-containing local anesthetic gave rise to rapid increases in the heart rate and blood pressure within a few seconds of the injection. Such cardiovascular responses, in many instances, were unacceptable to the subject because of the tachycardia and a feeling of intense tightness across the thorax. With Noradrenalin, on the other hand, the cardiovascular responses were asymptomatic, although it was usual for the heart rate to fall while the peripheral resistance and the blood pressure increased. Direct comparison was made, in the same persons, of infiltration and intraosseous injection of a Noradrenalin-containing local anesthetic. Insignificant responses were found with infiltration injections of catecholamines (0.9 ml. of 1/80,000 solutions) which is in agreement with previously published data. However, similar solutions injected intraosseously elicited cardiovascular responses. Although intraosseous injection of lidocaine hydrochloride containing 1/80,000 Noradrenalin appears clinically acceptable, a further search for anesthetics without effects on the cardiovascular system is desirable.

Comparative circulatory effects of adrenaline and noradrenaline during intra-osseous dental anaesthesia.

The effects of intra-osseous dental anaesthesia on heart rate and blood pressure was examined in 17 healthy volunteers. Adrenaline containing anaesthetic solutions were accompanied by increased heart rate and elevated systolic blood pressure which were not acceptable to a high proportion of subjects. Noradrenaline at the same concentration as adrenaline (1/80 000) usually decreased the heart rate and elevated the blood pressure. A few subjects experienced a feeling of weakness in the lower extremities when noradrenaline was injected. Endogenous catecholamine formation in these test conditions gave rise to insignificant circulatory effects.