Influence of a new propranolol analogue on the rabbit myocardium in vitro

Experiments with electrophysiology of the heart have been essential for the progress in diagnostics and pharmacotherapy of cardiovascular diseases. The aim of the study was to establish the influence of a new propranolol analogue on mechanical and bioelectrical activity of the rabbit heart in vitro. In the experiment, propranolol (1-isopropylamino-3-[1-naphthoxy]-2-propanol hydrochloride) and its newly synthesized analogue (1-[1,1-dimethyl-ethyl-amino]-3-[1-naphthoxy]-2-propanol hydrochloride) were used. Atrial trabecules were cut from right rabbit atrium. Each preparation consisted of cardiomyocytes and sino-atrial node cells. Preparations were stimulated with square pulses of direct current at a voltage of 20V, rate of 2 Hz and 1 ms duration. Propranolol and its analogue were applied at gradded concentration 10(-2) M, 10(-3) M, 10(-4) M, 10(-5) M, 10(-6) M and 10(-7) M. Mechanical (force of contraction, time of contraction and relaxation) and bioelectrical (amplitude and duration of action potentials) activities were examined. Bioelectrical activity of preparations was recorded using intracellular microelectrodes. LD(50) for new analogue was determined. Analogue diminished force of contraction and shortened time of contraction and relaxation of myocardium and decreased amplitude and duration of action potentials in sino-atrial node cells. It influenced mechanical and bioelectrical parameters to lesser degree than propranolol.