Comparison of Cross-Linked Hemoglobin Solution to Lactated Ringers and 5% Albuminin Resuscitation of a Rat Model of Escherichia coli Septic Shock

摘要

Intramolecularly cross-linked hemoglobin (lysine 99 alpha 1-lysine 99 alpha 2cross-linkage) has been reported to have oxygen transport properties similar to those of whole blood. Partial and complete transfusions in swine have demonstrated that cross-linked hemoglobin solutions transport oxygen and allow normal cardiac and renal function in the virtual absence of red blood cells. Recently, a study of this cross-linked hemoglobin solution in a rat model of hemorrhagic shock showed an improved hemodynamic response to cross-linked hemoglobin solution over that provided by lactated Ringers (R/L) solution. The hemodynamic response was similar to that of autologous whole blood infusion. In the present study we have attempted to utilize a cross-linked hemoglobin solution in resuscitation of a rat septic shock model. Sprague-Dawley rats were anesthetized with ketamine and injected i.p. with E. coli. Two hours after E. coli challenge the animals were resuscitated with either 7% cross-linked hemoglobin, 5% albumin or R/L at 1 0 cc/kg or 40 cc/kg. Hemodynamic parameters were monitored for up to five hours on the anesthetized animals. There were no significant differences between any treatment groups for heart rate, mean arterial pressure (MAP), cardiac output, or regional blood flow to tissues. In conclusion, the true benefits of stroma-free hemoglobin (SFH) resuscitation could not be properly assessed in this pilot study because of the role of ketamine anesthesia and fluid maintenance given to the animals prior to the administration of the SFH, human albumin (HA), and R/L resuscitative solutions. During the course of this experiment additional in vitro studies were done that showed that SFH potentiated the growth of pathogenic bacteria.