| Objective: Rat exchange transfusion model was used to study the efficiency of releasing oxygen on glutaradehyde-polymerized hemoglobin with different value of P50. Rat's live time was used to estimate the efficiency of poly-Hb, and then investigate pharmacodynamics of poly-Hb initially. In order to investigate the effect of poly-Hb on toxicity, 64kD tetramer hemoglobin (Tetra-Hb) was chosen as a material to observe its effect on blood pressure . Furthermore, the nitroglycerin which was used to control blood pressure in clinical was also used in our study and we also determine the minimum dosage of Tetra-Hb which could improve the pressure. We could determine the concentration of Tetra-Hb could affect on blood pressure and provide the data on the study of toxicology.Methods: In the experiment of pharmacodynamics, three kinds of poly-Hb with different value of P50 were produced and the concentration was 11g/dL. The exchange transfusion rat models were established and were divided into three groups randomly (poly-Hb-H, poly-Hb-M, poly-Hb-L). During the process of transfusion, the indexes of rat's blood gas could be detected, and the efficiency of releasing oxygen could be calculated. The rat's live time could be observed when Rat-Hb was less than 0.5g/dL. In order to research the toxicology of poly-Hb, glutaradehyde-crooslinked porcine hemoglobin which was 64kD tetramer has been produced. Physiologic saline and hydroxyethly starch were used as control and the changes of rat's blood pressure were recorded when tetramer poly-Hb was injected into rat with speed of 0.02mL/min through rat's jugular and femoral vein. Moreover, the changes of blood pressure could be observes in the process of injecting the nitroglycerin and tetramer hemoglobin in the same speed as mention above.Results: With the increasing of value of P50, the efficiency of releasing oxygen of poly-Hb could be enhanced. When the concentration of poly-Hb was 90% in rats, the efficiencies of releasing oxygen of poly-Hb-H and poly-Hb-M were more than 80%, but the poly-Hb-L was less than 50%. The released oxygen ability of poly-Hb-H was the fastest, but rat's live time was shorter. poly-Hb-L could not released oxygen effectively and rats dead soon after exchange transfusion. Only poly-Hb-M could release oxygen effectively, so that rat can live longer than 4 hours. Blood pressure could be raised by tetra-Hb obviously, but rat's MAP could be 15-20mmHg higher than baseline. Meanwhile blood pressure improving could be inhibited by nitroglycerin. And blood pressure could be raised less than 5mmHg when the concentration of Tetra-Hb was lower than 8mg/kg.w.Conclusions: Pharmacodynamics experiment suggested that oxygen affinity of poly-Hb and its efficiency of releasing oxygen in vivo were determined by the value of P50. No matter the value of P50 is high or low, it could not satisfy organism's need. Only poly-Hb with middle value of P50 (11mmHg) could provide oxygen for tissue and keep rat live longer. In our study, we found that the blood pressure could be raised by 64kD Tetra-Hb in rats. Blood pressure rising could be inhibited by nitroglycerin, and a large dose of Tetra-Hb which could stimulate blood pressure would be correlated with NO scavenging has been proved in advanced. But minimum dose (8mg/kg.w) of Tetra-Hb could also stimulate blood pressure which was not in agreement with the theory of NO scavenging. So, it still need do a further research on blood pressure in related to hemoglobin based oxygen carriers. |
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