title: The effect of calcium on hypothermia-facilitated resuscitation of warm ischemic kidney tissue slices: a role for the mitochondrial permeability transition pore?
abstract: This study examined the effect of varying the calcium (Ca) content of a solution used for aerobic hypothermic storage of rabbit kidney cortex tissue slices previously injured by 1-h warm ischemia. Ischemic slices were stored in UW Na-gluconate solution for 18 h at 5 degrees C with 0.5, 1.5, or 1.75 mM Ca (+/- quinacrine; 100 microM) followed by warm (37 degrees C) aerobic incubation in physiologic buffer for 3.5 h to simulate reperfusion. There was no effect of solution Ca concentration on tissue ATP (adenosine 5'-triphosphate) and nonesterified fatty acid (NEFA) content during reperfusion. However, recovery of slice ATP and NEFA content to control levels was seen with addition of quinacrine to hypothermic storage medium containing either 1.5 or 1.75 mM Ca but not with 0.5 mM Ca storage medium. Treatment of tissue slices with cyclosporine A (20 microM), an inhibitor of the mitochondrial Ca-induced permeability transition pore, abolished the resuscitative benefits of hypothermic preservation with quinacrine + 1.5 mM Ca. These results suggest that quinacrine exerts its effects on warm ischemic tissue during hypothermic storage via the mitochondrial permeability transition pore. An effect utilizing a pore-open state is probable but it remains unclear if quinacrine acts on the pore directly or gains access to the matrix space through the pore and exerts its effects via an unknown mechanism. These results indicate that resuscitative hypothermic storage methods may be able to use manipulation of the permeability transition pore as a valuable adjunct to pharmacologic treatments administered during hypothermia.
authors.affiliation: Department of Surgical Sciences, University of Wisconsin, Madison 53706-1102, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: McAnulty
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000332:Aerobiosis; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D003080:Cold Temperature; D016572:Cyclosporine / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D066298:In Vitro Techniques; D007511:Ischemia / Q000188:drug therapy* / Q000378:metabolism; D007672:Kidney Cortex / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D011796:Quinacrine / Q000494:pharmacology; D011817:Rabbits; D015427:Reperfusion Injury / Q000517:prevention & control; D012996:Solutions; D014021:Tissue Preservation
chemical_list: D005230:Fatty Acids, Nonesterified; D012996:Solutions; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D011796:Quinacrine; D002118:Calcium