Further observations on the cardiotoxicity of isoprenaline during hypoxia.

1 In dogs respired with 10% oxygen: 90% nitrogen, only five out of 16 dogs survived repeated intravenous doses of isoprenaline (either 0.5 or 1.0 mug/kg) and only one out of six dogs survived repeated isoprenaline inhalations from a pressurized aerosol.2 In dogs respired with 15% oxygen: 85% nitrogen, five out of six dogs survived repeated intravenous doses of isoprenaline (2.5 mug/kg).3 The fatal response in these animals consisted of a fall in heart rate, arterial and pulse pressures. Sinus rhythm persisted even after the arterial pressure had fallen, though occasionally a slow A-V nodal rhythm or irregular ventricular ectopic beats occurred. Ventricular fibrillation did not occur.4 Eight out of 10 dogs brought to the verge of a fatal response with 10% oxygen: 90% nitrogen and repeated doses of isoprenaline (2.5 mug/kg) were resuscitated by the administration of 100% oxygen and, when necessary, cardiac massage.5 A group of five dogs survived the combined effects of repeated doses of isoprenaline (2.5 mug/kg) and respiration with 10% oxygen: 90% nitrogen when the time interval between doses was 11 min, instead of the usual 5 minutes.6 Control of pH by infusion of sodium bicarbonate did not protect the dogs from the combined effects of hypoxia and repeated isoprenaline challenge.7 After a 60 min period of continuous isoprenaline infusion in dogs breathing room air, only one of 10 dogs survived artificial respiration with 10% oxygen: 90% nitrogen and repeated challenge with intravenous isoprenaline (1.0 mug/kg) at 5 min intervals. At the higher infusion levels of isoprenaline (0.1 and 1.0 mug kg(-1) min(-1)), two dogs out of four died after the hypoxic mixture was started but before any isoprenaline challenge was given.8 The possible relevance of these findings in dogs to the recently observed increase in mortality in young asthmatics is discussed.