Uncoupling mitochondrial activity maintains body (V) over dotO2 during hemorrhage-induced O2 deficit in the anesthetized rat

During a hemorrhagic shock (HS), O-2 uptake ((V) over dot(O2)) decreases as soon as the rate of O-2 delivery (D-O2) drops below a critical level, a response accounted for by the reduction in mitochondrial O-2 supply. In urethane-anesthetized rats, D-O2 was decreased within 20 min from 21.5 to 2.8 ml min(-1) by slowly withdrawing 18 ml kg(-1) of blood. This led to a reduction in (V) over dot(O2) from 6.1 to 2.4 ml min(-1) (n=5, p <0.01). Decoupling mitochondrial oxidative activity by injecting 2,4-DNP (6 mg kg(-1), iv) before HS elevated (V) over dot(O2) to 11.9 +/- 1.2 ml min(-1) (n= 6, p < 0.01), which remained above control HS values throughout most of the hemorrhage. This was associated with higher levels of O-2 extraction, cardiac output and ventilation than in control HS. D-O2 -(V) over dot(O2) relationship was shifted upward and to the left following DNP. In conclusion, cellular and systemic mechanisms, decreasing O-2 demand, account for a large part of HS induced (V) over dot(O2) decline resulting in an additional reduction in D-O2. (C) 2013 Elsevier B.V. All rights reserved.