Development of the rabbit model for studying the effects of propranolol on cardiac contractility: relationship of intravenous pharmacodynamics and pharmacokinetics.

The New Zealand white rabbit (3-4 kg) was chosen as an experimental model to determine the effects of propranolol, by intravenous bolus administration, on cardiac contractility. The cardiovascular effects were measured by systolic time interval recordings for up to 8 h. The study was performed on two groups of animals with 5 rabbits receiving active drug and another 5 rabbits receiving saline placebo. All animals were anesthetized by parenteral administration of urethane/acepromazine. The results indicated that at 15 min after intravenous administration, propranolol caused a maximum decrease in heart rate (p less than 0.01), as well as a maximum increase in QS2 (p less than 0.01), LVET (p less than 0.01), PEP (p less than 0.01) and PEP/LVET (p less than 0.05). Approximately 90 min after drug administration, a significant (p less than 0.01) "rebound phenomenon" was observed in the active group which continued throughout the 8-h observation period. This preliminary study suggests that the rabbit is a useful animal model to study the effects of propranolol on cardiac contractility.