The effects of hydrogen-ion concentration on the respiratory efficiency of human liver mitochondria.

To examine the effects of hydrogen ion concentrations on the coupled respirations of isolated human liver mitochondria, eight patients underwent incidental liver biopsies during the conduct of abdominal surgery. Mitochondria were studied by the polarographic technique at pH of 5.5, 6.0, 6.5, 7.0, 7.5, and 8.0. Results indicated severe inhibition of nicotinamide adenine dinucleotide (NAD)-linked substrates but succinate oxidations were minimally affected. Sodium succinate was then studied as a possible substrate in the resuscitation of hemorrhagic shock. Rats were subjected to bleeding to an arterial blood pressure of 50 mm Hg for 3 hours or until 25 per cent of shed blood had to be reinfused to maintain blood pressure. Resuscitation consisted of reinfusion of all shed blood plus a volume of one of four crystalloid regimens: Ringers lactate; isotonic sodium succinate; hypertonic sodium chloride (190 mEq/l): or twice-normal, hypertonic sodium chloride (308 mEq/l). Results indicated that those rats resuscitated with sodium succinate did poorer than animals receiving alternate regimens. The failure of succinate to diffuse across the plasma membrane may explain these data. Additional studies with succinate or a chemical analogue seem warranted.