Persistent reduced oxygen requirement following blood transfusion during recovery from hemorrhagic shock

• The O2 deficit progressively accumulated during a period of severe bleeding persists well after blood reperfusion.
• We found that O2 availability is not the main controller of V˙O2 dynamics after blood transfusion.
• The mechanism of slow recovery of O2 debt repayment following the restoration of normal O2 transport and delivery after blood transfusion following a severe hemorrhage remains unclear.

Our study intended to determine the effects on oxygen uptake (V˙O2) of restoring a normal rate of O2 delivery following blood transfusion (BT) after a severe hemorrhage (H). Spontaneously breathing urethane anesthetized rats were bled by removing 20 ml/kg of blood over 30 min. Rats were then infused with their own shed blood 15 min after the end of H. At mid-perfusion, half of the rats received a unique infusion of the decoupling agent 2,4-dinitrophenol (DNP, 6 mg/kg). V˙O2 and arterial blood pressure (ABP) were continuously measured throughout the study, along with serial determination of blood lactate concentration [La]. Animals were euthanized 45 min after the end of reperfusion; liver and lungs were further analyzed for early expression of oxidative stress gene using RT-PCR.Our bleeding protocol induced a significant decrease in ABP and increase in [La], while V˙O2 dropped by half. The O2 deficit progressively accumulated during the period of bleeding reached −114 ± 53 ml/kg, just before blood transfusion. Despite the transfusion of blood, a significant O2 deficit persisted (−82 ± 59 ml/kg) 45 min after reperfusion. This slow recovery of V˙O2 was sped up by DNP injection, leading to a fast recovery of O2 deficit after reperfusion, becoming positive (+460 ± 132 ml/kg) by the end of the protocol, supporting the view that O2 supply is not the main controller of V˙O2 dynamics after BT. Of note is that DNP also enhanced oxidative stress gene expression (up-regulation of NADPH oxidase 4 in the lung for instance). The mechanism of slow recovery of O2 requirement/demand following BT and the resulting effects on tissues exposed to relatively high O2 partial pressure are discussed.