Uncoupling mitochondrial activity maintains body VO2 during hemorrhage-induced O₂ deficit in the anesthetized rat

During a hemorrhagic shock (HS), O₂ uptake (VO2) decreases as soon as the rate of O₂ delivery (DO2) drops below a " critical level" , a response accounted for by the reduction in mitochondrial O₂ supply. In urethane-anesthetized rats, DO2 was decreased within 20min from 21.5 to 2.8mlmin^-1 by slowly withdrawing 18mlkg^-1 of blood. This led to a reduction in VO2 from 6.1 to 2.4mlmin^-1 (n=5, p<0.01). Decoupling mitochondrial oxidative activity by injecting 2,4-DNP (6mgkg^-1, iv) before HS elevated VO2 to 11.9±1.2mlmin^-1 (n=6, p<0.01), which remained above control HS values throughout most of the hemorrhage. This was associated with higher levels of O₂ extraction, cardiac output and ventilation than in control HS. DO2-VO2 relationship was shifted upward and to the left following DNP. In conclusion, cellular and systemic mechanisms, decreasing O₂ demand, account for a large part of HS induced VO2 decline resulting in an additional reduction in DO2.