Wakefield T W, Kirsh M M, Till G O, Brothers T E, Hantler C B, Stanley J C
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109.
J Surg Res. 1991 Jul;51(1):72-6. doi: 10.1016/0022-4804(91)90072-t.
Protamine reversal of heparin anticoagulation is associated with adverse hemodynamic effects that may be attenuated with protamine pretreatment (PP). This study assesses the role of complement activation during these phenomena in adult cardiac surgery patients. Sixteen individuals undergoing cardiopulmonary bypass were given intravenous normal saline or protamine (2 mg/kg) as a randomized pretreatment prior to undergoing heparin anticoagulation (400 IU/kg), coronary artery revascularization, and subsequent reversal of the anticoagulated state with protamine (4 mg/kg). Blood pressure, pulmonary artery diastolic pressure (PAD), heart rate, and cardiac output (CO) were measured during and after pretreatment, prior to heparin reversal by protamine, and for 10 min after reversal. Total hemolytic complement (CH50), C3 conversion to C3b, C3a/C5a, platelet count, and white blood cell count (WBC) were also measured at the same time periods. No significant correlation existed between complement activation and hemodynamic events, as might have been evident by decreased CH50, increased C3 conversion to C3b, or elevations in C3a/C5a levels. PP significantly prevented the CO decrease occurring at 1 and 3 min following heparin reversal by protamine (-0.8 and -1.4 liters/min vs 0.1 and -0.2 liters/min, P less than 0.05 and P less than 0.01, respectively). Reversal hypotension was less with PP, although PAD fell equally in both groups. WBC decreases after heparin reversal were less after PP (-25% vs -7%, P = 0.06). These data support the conclusion that, contrary to earlier reports, adverse hemodynamic and hematologic responses accompanying protamine reversal of heparin anticoagulation do not appear to be correlated with activation of complement. In fact, those patients having the greatest C3a generation exhibited the least hemodynamic changes.
鱼精蛋白逆转肝素抗凝作用与不良血流动力学效应相关，而鱼精蛋白预处理（PP）可能会减轻这些效应。本研究评估了成年心脏手术患者在这些现象中补体激活的作用。16例接受体外循环的患者在进行肝素抗凝（400 IU/kg）、冠状动脉血运重建以及随后用鱼精蛋白（4 mg/kg）逆转抗凝状态之前，随机接受静脉注射生理盐水或鱼精蛋白（2 mg/kg）作为预处理。在预处理期间及之后、鱼精蛋白逆转肝素之前以及逆转后10分钟测量血压、肺动脉舒张压（PAD）、心率和心输出量（CO）。同时还在相同时间段测量总溶血补体（CH50）、C3向C3b的转化、C3a/C5a、血小板计数和白细胞计数（WBC）。补体激活与血流动力学事件之间不存在显著相关性，这可能表现为CH50降低、C3向C3b的转化增加或C3a/C5a水平升高，但并不明显。PP显著预防了鱼精蛋白逆转肝素后1分钟和3分钟时出现的CO降低（分别为-0.8和-1.4升/分钟，而未预处理组为0.1和-0.2升/分钟；P<0.05和P<0.01）。PP组逆转低血压情况较轻，尽管两组的PAD下降程度相同。PP后肝素逆转后WBC减少幅度较小（-25% vs -7%，P = 0.06）。这些数据支持以下结论：与早期报告相反，鱼精蛋白逆转肝素抗凝作用时伴随的不良血流动力学和血液学反应似乎与补体激活无关。事实上，那些C3a生成最多的患者血流动力学变化最小。
