Pharmacological Reviews, Vol 4, 43-84, Copyright © 1952 by the American Society for Pharmacology and Experimental Therapeutics

EXPERIMENTAL CARDIAC ARRHYTHMIAS AND QUINIDINE-LIKE DRUGS

¹ The Nuffield Institute for Medical Research, University of Oxford, England

1. The methods of producing cardiac arrhythmias in experimental animals have been surveyed from the point of view of the variables which determine whether an arrhythmia results. These include the level of the blood pressure, the oxygen saturation of the blood, myocardial damage and perhaps the endogenous secretion of sympathomimetic amines.

2. Some of the methods for producing cardiac arrhythmias, such as the use of barium chloride, the veratrum alkaloids and aconitine, suggest an analogy with nervous tissue, in which these substances cause repetitive discharges, supernormality and an increase in the negative after-potential. This is only part of the evidence which suggests that many of the variables which influence the outcome of these and other procedures in the intact animal may have a common basis in their effect on the membrane potentials of individual cardiac muscle fibres.

3. The meaning of the term "ectopic focus" has been examined. Two hypotheses which may explain the origin of discharges from an ectopic focus were considered in relation to the experimental evidence.

4. In the light of the evidence outlined above, the prerequisites for a therapeutic agent to prevent or arrest arrhythmias have been discussed, and the methods used for measuring "quinidine-like" activity criticised. There seems little likelihood of removing these methods from their present empirical foundation without further knowledge of the behaviour of single myocardial cells. In the meantime it is desirable to recognize the tacit assumptions on which these methods are based.