Non-invasive measuring of the circulatory effect of afterload reduction in order to monitor the pharmacodynamic effect of drugs in normal volunteers.

In order to measure the effect of a decrease in afterload on systolic time intervals, left ventricular end-systolic diameter, and left ventricular wall stress, eight healthy young persons underwent a randomised placebo controlled trial of terbutaline before and during atenolol treatment. Pre-ejection period index, left ventricular end-systolic diameter, and wall stress all decreased after terbutaline, the decrease being clearly dose dependent. This was identical before and during atenolol administration. Consequently the observed changes were induced by beta-2 elicited vasodilatation, possibly combined with some decrease of parasympathetic tone. A close correlation between changes in pre-ejection period index (PEPI) and changes in left ventricular end-systolic diameter (LVESD) and wall stress was shown both before and during atenolol treatment. When using non-invasive methods in the evaluation of changes in contractility, it is important to correct for changes in preload and afterload. For normal subjects it is suggested that the relation between delta PEPI and delta LVESD as a percentage of the mean values should be used for evaluation of afterload changes. A method is suggested for estimating changes in pre-ejection period index induced by changes in left ventricular end-systolic diameter or wall stress.