Bisaramil and antiarrhythmics as inhibitors of free radical generation

The aim of this study was to investigate the effect of bisaramil--an antiarrhythmic drug under clinical trials-on free radical generation of isolated polymorph neutrophil granulocytes (PMN) and furthermore to compare its activity to that of well-known antiarrhythmics which have different modes of action. PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-acetate. Stimulated free radical generation capacity of PMNs and the time lag necessary for the initiation of free radical production were measured. All compounds were used at the concentrations of 10, 25, 50, 75, 100 micrograms ml-1. None of the antiarrhythmics stimulated by itself the free radical generation. Bisaramil exerted concentration dependent inhibitory effect on PMA-stimulated free radical generation and prolonged the time lag concentration dependently. At the investigated concentration range of antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity to bisaramil, but clear concentration dependency could not be seen in any of the cases. According to the results of this study inhibition of the stimulated free radical production of isolated PMNs cannot be closely connected merely to either membrane stabilizing or Ca-antagonistic activity of drugs. In vitro and earlier measured in vivo inhibitory action of bisaramil on free radical generation indicate a possible cardioprotective effect existing independently from its antiarrhythmic one. This observation may be important in outlining of the clinical indication field of bisaramil, and may be useful in the treatment of reperfusional damage.