The Electrocardiogram in the Assessment of the Effect of Drugs on Cardiac Arrhythmias

Abstract

upon Tyne NE7 7DNThe search for the ideal antiarrhythmic drug continues since none of the available agents offers optimum antiarrhythmic therapy. The continuing search coupled with the interest in the mechanisms of cardiac arrhythmias has led to the development of new techniques for the study of arrhythmias and antiarrhythmic drugs. In this article it is proposed to discuss the electrocardiographic methods used in the assessment of antiarrhythmic drugs. Firstly, to discuss the electrocardiogram in the assessment of the clinical electrophysiological properties of a drug and secondly, the electrocardiogram in the assessment of the value of the drug in the management of cardiac arrhythmias in man. Assessment of the electrophysiological effects of drugs Standard ECG intervalsThe standard electrocardiogram can give some information on the effects of a drug on automaticity and conduction velocity within the heart by analysis of the standard ECG intervals-P-P (or R-R), PR and QRS intervals (Table 1).The P-P interval reflects intrinsic sinus node function and the autonomic influences on the sinus node. Thus, any change in the P-P interval following drug administration can be a direct effect of that drug on sinus node function, or by its effect on the autonomic nervous system either directly or through reflex mechanisms. Thus, antiarrhythmic drugs such as quinidine and disopyramide can influence the P-P interval by their direct depressant effect on the sinus node, by their anticholinergic effects or by reflex autonomic changes as a result of a fall in systemic pressure.The P-R interval represents conduction through the atria, AV node and His purkinje tissue and changes in the PR interval following drug administration could reflect changes in any of these. However, because there is a difference in conduction velocity in the AV node and His purkinje system (it takes 100-120 ms for the impulse to cross the AV node and approximately 40 ms to traverse the His purkinje system), major changes in conduction in the His purkinje system have to occur before they are detected on the standard ECG run at conventional paper speeds of 25-50 mm/s. For example, a 10% change in AV nodal conduction may result in a change of 10-12 ms in PR interval, but a 10% change in His purkinje conduction will only be in the region of 4 ms. Thus, significant changes in His purkinje conduction can occur without being detected on the standard electrocardiogram.QRS duration reflects conduction through the ventricular myocardium and any change reflects changes in ventricular muscle conduction-e.g. procainamide prolongs QRS duration.Since the QT interval represents ventricular repolarization, analysis of the QT interval gives some information on the effect of the drug on ventricular repolarization time. Since repolarization time is dependent on heart rate it can be corrected for rate by formulas of Bazett (1920) or in children by that of Fraser, Froggatt & James (1964). Drugs that prolong ventricular repolarization such as amiodarone or quinidine will prolong...