Study Of Safety And Efficacy Of Glutaraldehyde-polymerized Porcine Hemoglobin

Objective: To investigate the response of blood pressure on molecular weight and the resuscitation of hemorrhagic shock on rats with glutaraldehyde-polymerized porcine hemoglobin (Poly-pHb).Methods: SD male rats (295±15g) have been used to executing fifty percent isovolemic exchange transfusion transfusions by different concentration lower P₅₀ intra-molecular cross-linked tetramer. The concentration of tetramer was 90mg/mL, 70mg/mL and 50mg/mL, respectively. Mean arterial pressure (MAP) was monitored continuously during the exchange transfusion and followed 30min.The content of tetramer was decided on the variation of the MAP. The same method has been used to studying different average molecular weight polymerized hemoglobin, including 250kDa, 500kDa, 800kDa, 1100kDa which are higher oxygen affinity have affected the Oxygen affinity. Blood has been drawn from femoral artery to inducing shock. The therapeutic effect of Poly-pHb was evaluated by comparing with other resuscitation fluids. After 30 minutes of ischemia , a kind of Poly-pHb (9mg/mL, P₅₀<10mmHg, MW=300kDa) was infused through the femoral vein as a treated group, and whole blood, Ringer's lactate and hydroxyethyl starch were infused respectively as the control group. Mean arterial blood pressure, heart rate and blood-gas were monitored at the time of baseline, end shock, 30 min, 60 min and 120 min after resuscitation, respectively.Results: It is showed that the MAP had been increased by 90mg/mL tetramer up to 20-25mmHg during 50% isovolemic exchange transfusion, and it is also showed that the MAP had hardly effected by the concentration of tetramer lower than 50mg/mL. During the isovolemic exchange transfusions, the MAP maintained stabilization in the infusion which molecular weight were 250kDa and 500kDa, while the MAP was decreased in the infusion which molecular weight were 800kDa and 1100kDa. It is showed that Poly-pHb has the similar therapeutic effects on hemorrhagic shock when compared with the whole blood, but it is better than any other controls.Conclusions: The MAP has been influenced by the concentration of tetramer and molecular weight in 50% isovolemic exchange transfusions. The blood pressure has been increased by the tetramer more than 90mg/mL, so we found the safety scope of concentration of tetramer is lower than 50mg/mL. And the MAP has been hardly influenced by the Poly-pHb with MW about 300kDa.While the MAP has been decreased by the additional MW of tetramer. The Poly-pHb is an effective therapeutic solution on hemorrhagic shock, and it is a perfect blood substitute in the future.