The cardio‐toxicity of isoprenaline during hypoxia

Abstract

The effects of the intravenous injection of isoprenaline on heart rate and arterial pressure has been studied in dogs artificially respired with room air or with 12% oxygen—88% nitrogen. In dogs breathing room air, isoprenaline in doses from 0.02 to 500 μg/kg increased heart rate and reduced arterial pressure. Ventricular fibrillation was produced in one out of three dogs given 250 μg/kg. This was the only dog breathing room air which was killed by isoprenaline. In dogs breathing room air the repeated intravenous injection at 5‐min intervals of 2.5 μg/kg increased heart rate and reduced arterial pressure. No ill effects were produced by six doses. In dogs respired with 12% oxygen—88% nitrogen the Pao2 was reduced from 84 to 38 mm Hg with no changes in Paco2. In these dogs death was produced by doses of isoprenaline which in dogs breathing room air produced normal responses. The fatal dose of isoprenaline (10–50 μg/kg) reduced heart rate and arterial and pulse pressures; sinus rhythm persisted until arterial pressure was less than 50 mm Hg. Ventricular fibrillation did not occur; death occurred from cardiac asystole. Death was produced in a similar way in dogs with hypoxaemia by giving four or five doses of isoprenaline (2.5 μg/kg) at 5‐min intervals or by two doses of 25 μg/kg. The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility. These lethal effects of isoprenaline could be prevented by pretreatment with propranolol.

Epidemiologic Studies of Beta Agonists and Asthma Deaths

“…The second group of possible mechanisms relates to the overuse of beta agonists in the situation of a life-threatening attack of asthma, in which the cardiac side effects are likely to be particularly harmful in the presence of severe hypoxia (1-3). In particular, Collins et al (13) showed that it was possible to administer large doses of isoprenaline intravenously to anaesthetized dogs with normal blood gas tensions without producing serious arrhythmias, whereas much smaller doses caused fatal cardiac depression during hypoxemia. The response involved asystolic arrest and was the same as that observed with more severe hypoxemia alone.…”

Accidental Intramuscular Isoprenaline in Early Pregnancy: The Effects, Management and Outcome

“…Death was produced in a similar way in animals with hypoxaemia by giving four or five doses of isoprenaline (2·5 ìg/kg) at five minutes intervals or by two doses of 25 ìg/kg. The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility 9 .…”

Further Observations on the Cardiotoxicity of Isoprenaline During Hypoxia

“…The electrocardiogram showed that, in most cases, sinus rhythm persisted even after the arterial pressure had fallen, though occasionally a slow A-V nodal rhythm or irregular ventricular ectopic beats occurred. It has previously been shown that within seconds of the fatal dose, there was a sharp decrease in cardiac output and stroke volume, accompanied by increases in ventricular end-diastolic pressures, indicating a failure of myocardial contractility (Collins et al, 1969;Swanton, 1972). The terminal response developed suddenly: cardiac output, stroke volume, and right and left ventricular responses to the penultimate dose have been shown to be relatively normal, though there was some reduction in heart rate and arterial pressure responses with repeated doses of isoprenaline.…”

“…In an earlier study, Collins, McDevitt, Shanks & Swanton (1969) described cardiotoxic effects from the administration of intravenous isoprenaline to hypoxic dogs, often resulting in their death. It was found that dogs breathing room air could withstand the administration of repeated small doses or single large doses of isoprenaline (up to 500 pg/kg) with no ill effects.…”

“…Ten dogs were respired with 10% oxygen: 90% nitrogen and repeated doses of isoprenaline (2.5 jg/kg) were administered intravenously at 6 min intervals. When a potentially fatal response had been produced, as judged by the development of sinus bradycardia, slow A-V nodal rhythm or irregular ventricular ectopic beats and continuously falling blood pressure (Collins et al, 1969), pure oxygen was substituted for the 10% Table 2 Average changes (±s.e. mean) in heart rate, systolic and diastolic arterial pressure produced by the intravenous injection of a series of doses of isoprenaline (2.5,ug/kg) given at 5 min intervals in dogs respired Values for the 1st, 3rd, 5th, 7th and 9th doses are shown.…”