CALCIUM-CHANNEL BLOCKERS CORRECT IN-VITRO MITOCHONDRIAL TOXICITY OF CELLULOSE-ACETATE

We studied the action of rinse solutions from cellulose acetate hemodi alyzers on isolated mitochondria. We showed that concentrates from the rinses impaired the adenosine 5'-triphosphate (ATP) synthesis as refl ected by the decrease in respiration during state 3 and in P/O ratio. This impairment results from a calcium release from mitochondria that is induced by rinse solution concentrates. The release, triggering the mitochondrial calcium carrier, would explain the decrease in ATP synt hesis. Moreover, rinse solution concentrates hinder mitochondrial calc ium storage. The rise in cytosolic calcium in hemodialyzed patients ma y be related, at least in part, to these findings, since a lack of ATP impairs the ATP-dependent cellular calcium-extrusion pumps. We also s howed that calcium channel blockers, at therapeutically relevant doses , restore ATP synthesis and calcium storage in mitochondria impaired b y rinse solution concentrates. Finally, these in vitro results were co nfirmed by experiments on cells in culture proving that Diltiazem coun teracts the cytotoxicity of rinse solution concentrates. These finding s are consistent with observations that these drugs suppress the incre ase in leukocyte cytosolic calcium in dialyzed patients. Moreover, thi s would help explain the efficiency of calcium channel blockers in cel ls without L-calcium channels.