Abstract Body: Introduction: Hemorrhage remains a leading cause of preventable death in warfare and acute trauma. Given blood shortages, ongoing research is looking into successful artificial oxygen carriers. We engineered a non-globin heme-based molecule, the Bacterial Regulator of Carbon Monoxide Metabolism (RcoM), has oxygen carrier properties suitable for resuscitation in hemorrhagic shock.
Hypothesis: We hypothesize that resuscitation with RcoM would improve mean arterial pressure (MAP) in hemorrhagic shock.
Methods: A murine model of traumatic hemorrhagic shock was used to investigate the hemodynamic effects of RcoM. Mice were anesthetized with 1.5% isoflurane and received a laparotomy to induce soft-tissue trauma. The left femoral artery and vein were cannulated. The arterial cannula was used for blood pressure monitoring, and the venous cannula was used for bleeding and intravenous infusion. Upon stabilization, hemorrhage was induced by a 30-minute controlled pressure bleeding (25 to 40 mmHg) through the venous cannula then shock was maintained for another 30 minutes. This was followed by resuscitation infusion for 30 minutes by either lactated Ringer (LR) solution, human hemoglobin (HHb), or RcoM with a volume equal to the shed blood volume. The concentration was 2 mM for HHb and Rcom. Baseline MAP, post-resuscitation MAP, and MAP change were compared across the three groups using a one-way ANOVA.
Results: There was no difference in the ratio of shed blood volume to the total blood volume (26.8 ± 3.4% for LR (n=7), 26.0 ±2.6% for HHb (n=3) and 27.6 ± 1.3% for Rcom (n=5), p = 0.7295). There was no difference for the baseline MAP between LR (83.5 ± 5.7 mmHg), HHb (87.4 ± 3.0 mmHg) and Rcom (82.3 ± 1.9 mmHg, p = 0.2931). The post-resuscitation MAP was significantly higher for RcoM (67.0 ± 6.3 mmHg) and HHb (60.4 ± 16.0 mmHg) compared to LR (25.9 ± 21.4 mmHg, p = 0.0029). There was no difference between Rcom and HHb in the post-resuscitation MAP (p = 0.8573). The MAP increase during resuscitation was significantly higher for Rcom (25.6± 5.8 mmHg) compared to LR (-8.5 ± 21.6 mmHg, p = 0.0197), but the difference between the HHb (19.0 ± 23.2 mmHg) and LR (p = 0.1155) was not statistically significant.
Conclusion: This study demonstrates that resuscitation with RcoM supports the blood pressure in a murine traumatic hemorrhagic shock model, suggesting its potential application as a non-globin artificial oxygen carrier for hemorrhagic shock.