The effects of resuscitation with a blood substitute on vasomotor physiology in a swine model of arterial hemorrhage

Abstract

Introduction: The purpose of this study was to determine if a hemoglobin based oxygen carrier, HBOC-201, alters endothelial function and nitric oxide (NO) physiology following hemorrhagic shock. Methods: Swine (Sus scrofa) underwent catheterization of the aorta and the femoral, circumflex iliac, and pulmonary arteries. Control animals (n = 3) underwent instrumentation only. Study animals underwent hemorrhage to a mean arterial pressure (MAP) of 30 ± 5 mmHg; maintained for 45 minutes; resuscitated to baseline MAP and maintained for 4 hours. Resuscitation fluids included: Lactated Ringers (LR) (n = 8), Shed Blood (SB) (n = 8), Lactated Ringers, 40 cc/kg plus Shed Blood (LRSB) (n = 8), and HBOC (n = 8). At baseline, one, and four hours after resuscitation, acetylcholine (Ach) was infused through the circumflex iliac artery and vasorelaxation measured by M-mode ultrasound. NO levels were determined by chemiluminescent assay. Data were analyzed using repeated measures ANOVA with Tukey’s post-hoc analysis. Values listed are ± SEM, p values < 0.05 were considered significant. Results: All animals survived the experiment. HBOC, SB, and LRSB provided equivalent resuscitation. Animals receiving HBOC required the lowest resuscitation volume (HBOC – 14.6 ± 2.13 cc/kg; SB – 41.5 ± 3.49 cc/kg; LRSB – 76.4 ± 1.10 cc/kg p < 0.01). For all groups, the mean baseline diameter of the external iliac artery was 0.52 ± 0.01 cm. Maximal vessel contraction occurred at the completion of shock (mean 0.27 ± 0.01 cm). Vessel diameter (0.48 ± 0.01 cm) and response to acetylcholine (100% recovery of baseline diameter) was restored to normal in the SB and LRSB groups at the end of resuscitation. The HBOC group had persistent vasoconstriction (0.35 ± 0.02 cm) and diminished Ach response (21% recovery at end resuscitation, p < 0.01). No levels did not differ between study groups (p = 0.69). Conclusion: HBOC may be an alternative resuscitation agent in patients with hemorrhagic shock. Resuscitation with HBOC requires less volume than blood or crystalloid. These data suggest HBOC-201 has a vasoconstrictive effect without nitric oxide scavenging.