The effects of bisaramil and antiarrhythmics on free radical generation of isolated neutrophil granulocytes.
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 to compare its activity with well-known antiarrhythmics. PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-acetate. Free radical generation capacity of stimulated PMNs were measured. Bisaramil exerted a concentration dependent inhibitory effect on stimulated free radical generation. At the investigated concentration range of the antiarrhythmics only propafenon, mexiletine and diltiazem showed similar activity as bisaramil, but clear concentration dependency could not be seen in any of the cases. According to the results of this study inhibition of stimulated free radical production by isolated PMNs can not be closely related merely to either membrane stabilizing or Ca-antagonistic activity of drugs. In vitro inhibitory action of bisaramil on free radical generation indicates a possible cardioprotective effect existing independently of its antiarrhythmic one. This observation may be important in outlining the range of clinical indications of bisaramil as it may also be useful in the treatment of reperfusion injury.
Lantos
J
J
Department of Experimental Surgery, University Medical School of Péos, Hungary.
Röth
E
E
Paróczai
M
M
Kárpáti
E
E
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000008:administration & dosage / Q000494:pharmacology*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects; D002722:Chlorobenzenes; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D008801:Mexiletine / Q000008:administration & dosage / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D015427:Reperfusion Injury / Q000517:prevention & control; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002121:Calcium Channel Blockers; D002273:Carcinogens; D002722:Chlorobenzenes; D005609:Free Radicals; D013481:Superoxides; D008801:Mexiletine; D004110:Diltiazem; C045644:bisaramil; D013755:Tetradecanoylphorbol Acetate