Defective oxidative metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock.

MELA, LEENA, LEONARDO V. BACALZO, JR., AND LEONARD D. MILLER. Defective oxidatiue metabolism of rat liver mitochondria in hemorrhagic and endotoxin shock. Am. J. Physiol. 220(2) : 571477. 197 1 .-Rat liver mitochondrial functions were studied after hemorrhagic hypovolemia and Escherichia coli endotoxin shock. The respiratory activity in State 4 was increased indicating normal utilization of substrates and oxygen, but loose coupling. The electron-transfer reactions induced by substrates were unaltered. The respiratory rates in State 3, however, were inhibited in the presence of any of the substrates used, succinate, glutamate-malate, or aketoglutarate. Due to increased State 4 and decreased State 3 rates, the respiratory control ratios dropped from control values of 6-8 to about 2. The ADP utilization rate decreased parallel with the respiratory rates. Also, an addition of ADP to mitochondria prepared at final stages of shock failed to induce steady-state changes of the cytochromes. The mitochondrial uncoupler-sensitive ATPase activity was inhibited as well by 7075. All these alterations occurred both in hemorrhagic and endotoxin shock. The only significant difference was the dependence of the alterations on the length of the shock. The data suggest that the mitochondrial defect caused by shock is in the adenine nucleotide translocase and/or utilization mechanism in connection with the fault in ATPase activity.