Experimental study of the detrimental effect of dopamine/glucagon combination in d,l- propranolol intoxication

Abstract

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

2 The effect of glucagon, dopamine and the combination of glucagon/dopamine on respiratory and cardiovas cular function and survival time in β-blocker overdose was investigated in a model of acute d,l-propranolol (resp. 30 and 15 mg kg^-1 h^-1 in rat and rabbit) intoxication in spontaneously breathing rats and artifically ventilated rats and rabbits.

3 Glucagon (initial dose of 100 μg kg^-1 (bolus), followed by 1 μg kg ^-1 min^-1), dopamine (25 μg kg^-1 min^-1 ) or the combination of glucagon/dopamine did not im prove survival time (ST) in d,l-propranolol intoxicated spontaneously breathing rats and artificially venti lated rats and rabbits, although some haemodynamic variables i.e. heart rate (HR), mean arterial blood pressure (MAP), left ventricular pressure (LVP_max) and the differentiated left ventricular pressure (LVdp/ dt_max) temporarily improved.

4 Survival time was considerably reduced in d,l- propranolol intoxicated spontaneously breathing and artifically ventilated rats treated with a combination of glucagon /dopamine, which induced a decrease in PaO₂ and pH and an increase in PaCO₂ partly due to ventilation/perfusion mismatch.

5 The combination of glucagon/dopamine should be used carefully in the treatment of β-blocker overdose in man.