Granulocyte activation during haemodialysis in the absence of complement activation: inhibition by calcium channel blockers.
The effect of the calcium channel blockers nifedipine (9 and 18 micrograms kg-1 h-1), diltiazem (100 and 200 micrograms kg-1 h-1) and verapamil (19 micrograms kg-1 h-1) continuously infused during haemodialysis on granulocyte and complement activation was investigated. Plasma levels of lactoferrin, elastase in complex with alpha 1-proteinase inhibitor (E-alpha 1PI) and C3a were measured in patients dialysed with dialysers made of cuprophane, polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN). Calcium channel blockers caused no change of blood pressure during haemodialysis in all patients. There was no effect of nifedipine, diltiazem or verapamil on plasma lactoferrin, E-alpha 1PI or C3a levels in patients dialysed with cuprophane. However, plasma lactoferrin and E-alpha 1PI values were significantly reduced by all calcium channel blockers in patients dialysed with PMMA, and also by nifedipine and verapamil in patients dialysed with PAN. Our data indicate that calcium channel blockers inhibit granulocyte activation occurring in dialysers with very little anaphylatoxin formation. These drugs, however, are ineffective in patients dialysed with cuprophane where complement activation takes place. Therefore, granulocyte activation during haemodialysis in the absence of complement activation seems to be mediated by calcium ions.
D000368:Aged; D001798:Blood Proteins; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003167:Complement Activation; D005260:Female; D006098:Granulocytes / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007688:Kidneys, Artificial; D007781:Lactoferrin / Q000097:blood; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000097:blood; D006435:Renal Dialysis / Q000009:adverse effects*; D014511:Uremia / Q000097:blood / Q000188:drug therapy / Q000276:immunology; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D002121:Calcium Channel Blockers; D000515:alpha 1-Antitrypsin; D007781:Lactoferrin; D010196:Pancreatic Elastase