Abstract： Objective To explore the feasibility of using protamine-agarose gel to achieve heparin-free cardiopulmonary bypass （CPB）. Methods A total of 12 healthy adult dogs were chosen, the dogs were between 2-3 years old,either male or female, with their mean body weight of 23.3±3.7 kg （ranging from 20 to 28 kg）. All the dogs were randomly divided into two groups with 6 dogs in each group. In the heparinized group, conventional CPB technique was used; in the non-heparinized group, protamine-agarose gel column was used to absorb plasma clotting factors in CPB without use of heparin. At the beginning of CPB and 1 h, 2 h, 3 h after CPB, arterial blood samples were collected from dogs in both groups. The expression levels of tumor necrosis factor-α （TNF-α）, interleukin-6 （IL-6） and interleukin-8 （IL-8） were measured by enzyme-linked immunosorbent assay（ELISA）and compared. Results There was no thrombus formation in the membrane oxygenators during CPB by naked eye observation in both groups. Activated coagulation time （ACT） was always greater than 480 s during CPB. The vital signs of the dogs were all stable during CPB. At the beginning of CPB, there was no statistical difference in plasma concentrations of TNF-α, IL-6, IL-8 between the two groups. At 1 h, 2 h and 3 h after CPB, the expression levels of TNF-α and IL-8 of the non-heparinized group were significantly higher than those of the heparinized group （CPB 3 h TNF-α：156.48±16.65 ng/L vs. 115.87±15.63 ng/L, t=4.356, P=0.001；CPB 3 h IL-8：365.38±46.18 ng/L vs. 299.29±34.50 ng/L, t=2.808, P=0.019）. There was no statistical difference in the expression level of IL-6 between the two groups （P＞0.05）. Conclusion Using protamine-agarose gel to absorb plasma clotting factors is an effective technique to establish heparin-free CPB. But this method can induce significant systemic inflammatory response.
Abstract： Objective To compare individualized protamine with protamine based on weight in terms of postoperative bleeding and blood transfusion dose, in order to reduce postoperative bleeding complications. Methods Forty adult patients scheduled to elective open heart surgery under cardiopulmonary bypass （CPB） were randomly divided into two groups. For patients in the experimental group, we gave them protamine based on heparinprotamine titration result, while patients in the control group received the same amount of protamine as the heparin administered before operation. Pleural drainage and required transfusion were recorded at 1, 2 and 24 hours after surgery. Results Protamine dose given to the experimental group was significantly higher than the control group (Plt;0.05), while pleural drainage was significantly lower at 1 h(180±83 ml vs. 285±156 ml,P=0.012), 2 h (74±31 ml vs. 114±44 ml，P=0.002), and 24 h (465±167 ml vs. 645±207 ml，P=0.004) than that in the control group after surgery, and the required red blood cell suspension was also significantly lower than the control group (0.15±0.27 U vs.0.80±0.96 U,P=0.018). Conclusion Compared with protamine dose based on heparin administered before CPB, individualized protamine based on titration can reduce postoperative pleural drainage (blood loss) and red blood cell suspension requirement.
Protamine, which can be used to neutralize the anticoagulant effect of heparin in terms of surgical field extensively, is a kind of polycationic peptide extracted from the mature spermary of fish and mammal. While protamine brings convenience for clinical practice, it also produces some adverse reactions, which even endanger the patient's life. The clinical workers, therefore, pay more attention to the prevention and monitoring of adverse reactions of protamine. This paper introduces the mechanism of the interaction between protamine and heparin, monitoring methods and adverse reaction types. Furthermore, it reviews the current prevention methods of its adverse reactions, its application scale, as well as its existing problems in various clinical disciplines, suggesting that the modification of protamine from the perspective of molecular biology and genetic biology may strengthen its drug efficacy and reduce its adverse reactions, which will be the research highlights in the near future.