Study Of The Effects Of Polymerized Porcine Hemoglobin (pPolyHb) In Acute Anemia Models

Anemia is one of the most common clinical symptom of the disease. The severity of the symptoms is related to the degree of anemia and the rate of progression. Acute severe anemia can lead to tissue hypoxia injury or even death. Blood or blood products infusion is the main method of acute anemia curation. However, it is necessary to find appropriate blood substitutes due to the risk of blood infection, blood shortage and preservation.Hemoglobin-based oxygen carriers are compounds based on hemoglobin. Polymerized porcine hemoglobin (pPolyHb) is a new type of Hemoglobin-based oxygen carriers (HBOCs),which is synthesized from glutaraldehyde modified porcine hemoglobin. It has been used in hemorrhagic shock and 100% blood exchange transfusion and verified to be safety and capable of oxgen carrier and release. The objective of this study was to investigate the recovery ability of polymerized porcine hemoglobin (pPolyHb) in rats and canines models of acute anemia caused by normovolemic hemodilution (ANH).Firstly, the effects on severe anemia rat and resuscitation with pPolyHb were assessed from the aspects of mean arterial pressure (MAP) and arterial blood gas, 8 plasma analytes and histopathology. All experiments were conducted on pentobarbital-anesthetized SD rat. A rat model of acute anemia caused by normovolemic hemodilution (ANH) was performed.Exchange transfusions were performed at a rate of 0.3 ml/min. The target parameter for the hemodilution protocol was the animal’s Hb concentration. When the Hb concentration reached 4±0.5g/dL or 5±0.5g/dL,animals were randomized to receive a bolus infusion of either pPolyHb (n = 8) or red blood cells (RBC; n = 8). The target trigger for infusion was when the Hb concentration reached more than 7g/dL. MAP and arterial blood gas parameters were compared. Blood samples were withdrawn to evaluate ALT, AST et.al. Tissue samples of isolated kidney were taken for histological examination after 1d and 7d. During the phase of resuscitation, MAP returned to near baseline in the pPolyHb and RBC groups. In addition,pPolyHb as well RBC resuscitation significantly alleviated the metabolic acidosis and reduced activities of markers of liver and kidney injury. This improvement across all parameters tested was equivalent to that observed with RBC, but greater than that which occurred in a control group without infusion. The results showed pPolyHb and RBC could carry a sufficient amount of oxygen to the tissues to maintain normal aerobic metabolism and hemodynamic stability, without any significant toxic effects on renal and liver function according to pathological and biochemical analysis.In the canine normovolemic hemodilution model, anemia was performed by the same protocol of rat. When the Hb concentration reached 4±0.5g/dL, canines were randomized to receive a bolus infusion of either 3g/kg pPolyHb or NS. Hemodynamic parameters, arterial blood gas parameters, oxygen delivery and consumption and coagulation parameters were monitored.Blood samples were withdrawn to evaluate ALT, AST et.al after 7d. Tissue samples of isolated kidney and liver were taken for histological examination. pPolyHb is superior in maintaining hemodynamic stability than crystal liquid when RBC products were not a choose.Furthermore, pPolyHb could carry a sufficient amount of oxygen to the tissues to maintain normal aerobic metabolism and hemodynamic stability, without any significant toxic effects on renal and liver function according to pathological and biochemical analysis. The results showed pPolyHb could significantly improved acute anemia caused by isovolemic hemodilution in experimental canines.