Low-volume resuscitation with a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhage.

BACKGROUND: We have shown in a previous work that HBOC-201 is able to reverse anaerobic metabolism at low volumes in a porcine model of controlled hemorrhage. On the basis of these results, we hypothesize that low-volume resuscitation with HBOC-201 in a porcine model of controlled hemorrhage provides adequate tissue oxygenation to limit end-organ damage and allow for survival of the animal. METHODS: Twenty-four Yorkshire swine (55-65 kg) were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and then divided into four groups. The first group, Shed Blood (BL), was resuscitated with shed blood to baseline MAP. A second group, Shed Blood (60), underwent resuscitation for four hours at an MAP of 60 mm Hg with shed blood. The third group, LR + Blood, was resuscitated with lactated Ringer's (maximum, 40 mL/kg) followed by shed blood to baseline MAP. The final group, HBOC (60), underwent resuscitation for 4 hours at an MAP of 60 mm Hg with HBOC-201. Hemodynamic variables, urine output, blood gas analyses, lactate levels, and jejunal oximetry were followed throughout the experiment. Animals were allowed to survive and underwent necropsy on postinjury day 3. Histologic comparisons were made. Data were analyzed using analysis of variance/Duncan's multiple range test. RESULTS: All animals survived the hemorrhage/resuscitation. One animal in the LR + Blood group died on postinjury day 1. Heart rate, MAP, and arterial pH were similar between groups. Cardiac output was significantly lower throughout resuscitation in the HBOC (60) group. Jejunal oximetry was similar throughout the experiment in all groups, revealing a decline in Po2 during hemorrhage and return to baseline or near baseline during resuscitation. There was no evidence of renal dysfunction. Histologically, one animal in the LR + Blood group and four of six animals in the HBOC (60) group demonstrated mild hepatocellular damage. All other tissues examined were found to have no significant abnormalities. Elevations in serum aspartate aminotransferase levels were noted when comparing the HBOC (60) group to the Shed Blood (BL) and Shed Blood (60) groups on day 2. Significant decreases in hemoglobin levels were noted in the HBOC (60) group compared with all other groups beginning on day 2. CONCLUSION: Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.

The polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201) is not toxic to neural cells in culture.

BACKGROUND: Recent data suggest that a neurotoxic effect of blood or its components may contribute to secondary neural cell dysfunction. This study investigated the effects of HBOC-201 (Hemopure) and purified human hemoglobin (hHgb) on rat fetal neural cell culture. METHODS: Neural cell cultures were exposed to HBOC-201 and hHgb (0.02, 0.2, 2.0, and 6.5 g/dL) for 24 hours, and then analyzed for proliferation, metabolism, and neurolysis. RESULTS: Cultures exposed to HBOC-201 maintained levels of proliferation and metabolism similar to controls while demonstrating no cellular lysis. However, cultures exposed to hHgb demonstrated decreased proliferation after exposure to 0.2, 2.0, and 6.5 g/dL hHgb (14,252.14, 3,221.89, and 343.12 vs. 19,509.53; p< 0.05) when compared with controls. In addition, cultures exposed to hHgb demonstrated decreased metabolic activity and increased cell lysis when compared with controls (p < 0.05). CONCLUSION: Cultures exposed to HBOC-201 displayed sustained metabolic activity and proliferation, and demonstrated no neurolysis, suggesting that HBOC-201 does not display the toxic characteristics of hHgb.

Extracorporeal membrane oxygenation in piglets using a polymerized bovine hemoglobin-based oxygen-carrying solution (HBOC-201).

PURPOSE: The purpose of this study was to determine if the polymerized bovine hemoglobin-based oxygen-carrying solution HBOC-201 is an acceptable substitute for blood in a healthy porcine, extracorporeal membrane oxygenation (ECMO) model. METHODS: Ten piglets (15 to 25 kg) were placed on venoarterial ECMO. Four animals received blood-primed ECMO, and 6 animals received HBOC-201-primed ECMO. Hemodynamic variables, urine output, blood gas analyses, complete blood counts, and lactate levels were followed for 6 hours. Data were analyzed using a nonparametric sign test and repeated measures analysis of variance (ANOVA). RESULTS: All animals survived the 6-hour ECMO procedure. Heart rate, mean arterial pressure, urine output, and serum lactate levels were not significantly different between groups. Postpriming volume was 176 +/- 156 mL in the blood group. None of the animals in the HBOC-201 group required additional volume to maintain target flow during ECMO (P <.05). Arterial pH, pO2, and oxygen content between groups were not significantly different. Hematocrit for the HBOC-201 group was significantly (P <.05) lower than the blood group. CONCLUSIONS: HBOC-201-primed ECMO in a healthy porcine model showed similar hemodynamics and equivalent oxygen carrying capacity to blood-primed ECMO. Postpriming volume requirement was decreased significantly in the HBOC group. ECMO using HBOC-201 instead of blood appears promising and warrants further investigation.