A Preliminary Study On Pharmacodynamics Of Polymerized Porcine Hemoglobin(pPolyHb)

Hemoglobin Based Oxygen Carriers(HBOCs)are a kind of protein drugs,which are chemically modified and synthesized by human or animal hemoglobin.HBOCs carry and deliver oxygen to tissues,significantly improve oxygen supply,in addition to expanding intravascular volume and dramatically increasing the solubility of dissolved oxygen in blood,and furthermore,HBOCs do not need cross-matching and can be prepared virus-and bacteria-free which are currently the most promising red blood substitute.Polymerized porcine hemoglobin(pPolyHb)is cross-linked with glutaraldehyde and synthesized from chemically modified porcine hemoglobin.Large previous studies of pPolyHb have shown that pPolyHb maintained hemodynamic stability well and significant increased the oxygen supply for organization,alleviated anaerobic metabolism,and effectively sustained the lives of treated animal.At present,pPolyHb is in the stage of preclinical safety evaluation.As a kind of red blood substitute using for human,not only a thorough evaluation of pPolyHb’s safety is required,but also we should evaluate its effectiveness in the clinical trial.The effectiveness of pPolyHb on the situation of perioperative blood transfusion and outside-hospital uncontrolled hemorrhagic shock were explored through the establishment of related animal clinical trial model.We established the perioperative normovolemic hemodilution and perioperative "window period" animal model.During the perioperation,to restores the efficient volume,crystalloids and colloids have been used when the excessive bleeding for the surgical and other reasons.This solution transfusion could lead to constant volume blood dilution.Comparing to the conventional plasmasubstitute with no oxygen-carrying capabilities(10%Hetastarch[HES]200/0.5),pPolyHb could maintain hemodynamic stability well,adequately deliver oxygen to tissue,improveanimal long-term survival.During the perioperative period,patientsinneed of blood transfusions will wait a long period of time to get blood from the blood bank when a clinician decided to performblood transfusion for the patient.This period is referred to as the"window period".During the "window period",transfusion with pPolyHb could better maintained blood physiological and biochemical level well.After infusion of allogeneic blood,it will get better comparing with transfusion with hetastarch.The results showed that pPolyHb maybe a good candidate when blood is not available during the perioperative period.Hemorrhagic shock(HS)is the leading cause of death of trauma patients.We assessed the ability of pPolyHb in comparison with red blood cells(RBC)and hetastarch(HES)in a rat model of HS and observed the mesenteric microcirculation.The result showed pPolyHbmaintained hemodynamic stability well,reversed anerobic metabolism,adjusted electrolyte acid-base imbalance,and increased tissue oxygen,which is similar to red blood cells and better than HES.HS induces mesenteric microvascular constriction.Resuscitation with pPolyHb was able to correct the vasoconstriction promptly.These results provide database for future investigation of pPolyHb in clinical trials.