Reduced survival after isoprenaline/ dopamine in d,l-propranolol intoxicated rats

Abstract

1 Respiratory and cardiovascular failure are principle toxic effects of β-blocker overdose. Respiratory arrest is the primary cause of death in β-blocker intoxicated rats.

2 The effect of β-adrenoceptor agonists on respiratory and cardiovascular failure in β-blocker overdose was investigated in a model of acute d,l-propranolol (30 mg kg ^-1 h^-1) intoxication in spontaneously breathing rats.

3 Neither the aselective, hydrophilic β-agonist isoprena line (10, 25, 50 μg kg^-1 min^-1), nor the β ₁-selective, lipophilic β-agonist flerobuterol (1,3,10 μ g kg^-1 min^-1) and the β₂-selective, lipophilic β-agonist clenbuterol (10, 25, 50 μg kg^-1 min^-1) had any beneficial effect on cardiovascular and respiratory variables or survival time in d,l-propranolol intoxicated spontaneously breathing rats.

4 Isoprenaline (10 μg kg^-1 min^-1) had no favourable effect on haemodynamic and respiratory variables in artificially ventilated d,l -propranolol intoxicated rats either.

5 Addition of dopamine to isoprenaline resulted in a significant reduction of survival time, primarily caused by a decrease in mean arterial blood pressure, in artificially ventilated d,l-propranolol intoxicated rats. Addition of glucagon to isoprenaline did not affect survival time. 6 Artificial ventilation is the most important supportive measure in d,l-propranolol intoxication in the rat.