Polymerized human hemoglobin with low and high oxygen affinity in trauma models

Area of Science:

• Biomedical Engineering
• Trauma Research
• Resuscitation Science

Background:

• Severe trauma often leads to hemorrhagic shock (HS), requiring effective resuscitation strategies.
• Polymerized human hemoglobin (PolyhHb) is investigated as a blood substitute.
• Different conformational states of PolyhHb (tense and relaxed) may influence efficacy and toxicity.

Purpose of the Study:

• To compare the hemodynamic resuscitation efficacy of tense-state (T) and relaxed-state (R) PolyhHb after traumatic brain injury (TBI) and HS in rats.
• To evaluate the relative toxicity of T-state and R-state PolyhHb in guinea pigs (GPs) subjected to HS.

Main Methods:

• Wistar rats with TBI and HS were resuscitated with whole blood, T-state PolyhHb, or R-state PolyhHb.
• Guinea pigs subjected to HS were reperfused with either T-state or R-state PolyhHb.
• Hemodynamic parameters (MAP) and markers of vital organ damage (liver, kidney, cardiac) and inflammation were assessed.

Main Results:

• T-state PolyhHb and whole blood led to better mean arterial pressure (MAP) recovery in rats compared to R-state PolyhHb.
• R-state PolyhHb resuscitation in GPs increased markers of liver damage, kidney injury, and systemic inflammation.
• R-state PolyhHb also resulted in higher cardiac damage markers (troponin) in GPs.

Conclusions:

• T-state PolyhHb demonstrates superior hemodynamic restoration capabilities in a rat model of TBI and HS.
• T-state PolyhHb exhibits reduced vital organ toxicity compared to R-state PolyhHb in guinea pigs.
• These findings support the potential of T-state PolyhHb as a more effective and safer resuscitation fluid for severe trauma.