Autonomic block, cardiovascular depression and histamine release produced by polymyxin B in the cat

The present study quantifies the autonomic block, the cardiovascular depression and the histamine releasing effects of polymyxin B in nine anaesthetized cats. The dose requirements for 50 per cent depression of the mean arterial blood pressure, the bradycardiac response to vagal stimulation, and the contraction of the nictitating membrane elicited by pre-ganglionic and post-ganglionic stimulation of the cervical sympathetic trunk have a narrow range of scatter, being of the order of 6--12 mg.kg-1 of the polymycin B base. The neuromuscular blocking dose (ED50), previously determined and hereby confired, also falls in the same range. Bradycardia and possibly histamine release are also observable. The relatively unremarkable effect of polymyxin B on the heart rate can be attributed to the balance between the vagal, sympathetic and ganglionic blocks, as well as the possible histamine release. All effects are long-lasting. Thus lack of tissue specificity makes it implausible to explain the neuromuscular and the cardiovascular effects of polymyxin B solely by the cholinergic mechanism of action. Ganglionic block and histamine release do not completely explain hypotension induced by polymyxin B. We propose that all biological effects of polymyxin B derive from a common mechanism of action, which may be its antimembrane antibacterial action. We would like to alert anaesthetists to the possiblity that polymyxin B may cause severe multiple organ system depression, in addition to neuromuscular block.