FURTHER OBSERVATIONS ON THE CARDIOTOXICITY OF ISOPRENALINE DURING HYPOXIA

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Abstract
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 μg/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 μg/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 μg/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 μg/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 μg/kg) at 5 min intervals. At the higher infusion levels of isoprenaline (0.1 and 1.0 μg 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.