In vitro versus in vivo mitochondrial calcium loading in ischemic acute renal failure.
Progressive mitochondrial Ca2+ accumulation and respiratory dysfunction have been observed during reperfusion after renal ischemia. The present study demonstrated that normal mitochondria, isolated in the presence of high Ca2+ concentrations, are capable of accumulating large amounts of Ca2+ in vitro and exhibit depressed respiratory rates. Since mitochondria isolated from reperfused ischemic tissue may be exposed to high concentrations of Ca2+ during the isolation procedure, the present study examined the effect of in vitro versus in vivo mitochondrial Ca2+ loading on mitochondrial function during ischemic acute renal failure (ARF) in anesthetized rats. When ruthenium red was added during isolation to prevent mitochondrial Ca2+ exchange with the medium, mitochondrial Ca2+ increased from 10.8 +/- 0.3 to 65.6 +/- 11.6 nmol/mg (P less than 0.001) after 24 h of postischemic reperfusion; this resulted in a 47% reduction in the acceptor-control ratio (ACR) from 4.19 +/- 0.09 to 2.70 +/- 0.13 (P less than 0.001). These data were compared with an increase in mitochondrial Ca2+ from 52.5 +/- 2.9 to 167.6 +/- 25.4 nmol/mg (P less than 0.001) and a 95% fall in ACR (3.84 +/- 0.40 to 1.15 +/- 0.08, P less than 0.001) at 24 h of reperfusion when no ruthenium red was added. However, at each time point examined, in vivo mitochondrial Ca2+ accumulation was shown to account for 50% or more of the mitochondrial respiratory dysfunction observed during ischemic ARF.
P E
PE
Arnold
D
D
Lumlertgul
T J
TJ
Burke
R W
RW
Schrier
D058186:Acute Kidney Injury / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D002458:Cell Fractionation; D007511:Ischemia / Q000150:complications* / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000648:ultrastructure*; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology; D013997:Time Factors
D012430:Ruthenium Red