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 (LVPmax) and the differentiated left ventricular pressure (LVdp/ dtmax) 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.