Montalescot G, Fischman A J, Strauss H W, Wilkinson R A, Ahmad M, Fitzgibbon C, Robinson D W, Zapol W M
Department of Anaesthesia, Massachusetts General Hospital, Boston.
J Appl Physiol (1985). 1993 Aug;75(2):963-71. doi: 10.1152/jappl.1993.75.2.963.
Protamine reversal of heparin anticoagulation occasionally induces the release of thromboxane into plasma with catastrophic pulmonary hypertension. To examine the site of neutralization, we labeled protamine sulfate with 111In and compared activity scans after administration of labeled protamine in unheparinized and heparin-anticoagulated sheep. Protamine administration in sheep without prior heparinization did not cause thromboxane release, pulmonary hypertension, or significant leukopenia, and 111In-protamine was rapidly cleared from the lungs (half time 0.48 +/- 0.08 min). Neutralization of heparin anticoagulation by labeled protamine produced elevated plasma thromboxane, pulmonary vasoconstriction, leukopenia, and prolonged pulmonary clearance of 111In-protamine (half time 3.32 +/- 0.43 min). In rats, protamine reversal of heparin anticoagulation did not induce either thromboxane synthesis or pulmonary hypertension, and 111In-protamine cleared rapidly from the lungs. Thus the ovine heparin-protamine reaction produces concomitant pulmonary sequestration of heparin-protamine complexes, thromboxane release, and pulmonary vasoconstriction; this did not occur in the rat. The lung specificity of the reaction and interspecies differences suggest that ovine pulmonary intravascular macrophages may be activated by heparin-protamine complexes to release thromboxane and provoke acute pulmonary vasoconstriction.
鱼精蛋白逆转肝素抗凝作用偶尔会导致血栓素释放到血浆中，引发灾难性的肺动脉高压。为了检查中和位点，我们用铟-111标记硫酸鱼精蛋白，并比较了在未肝素化和肝素抗凝的绵羊中给予标记鱼精蛋白后的活性扫描结果。在未预先肝素化的绵羊中给予鱼精蛋白不会导致血栓素释放、肺动脉高压或显著的白细胞减少，并且铟-111标记的鱼精蛋白能迅速从肺部清除（半衰期为0.48±0.08分钟）。用标记的鱼精蛋白中和肝素抗凝作用会导致血浆血栓素升高、肺血管收缩、白细胞减少以及铟-111标记的鱼精蛋白在肺部的清除时间延长（半衰期为3.32±0.43分钟）。在大鼠中，鱼精蛋白逆转肝素抗凝作用既不会诱导血栓素合成也不会引发肺动脉高压，并且铟-111标记的鱼精蛋白能迅速从肺部清除。因此，绵羊的肝素-鱼精蛋白反应会伴随肝素-鱼精蛋白复合物在肺部的潴留、血栓素释放和肺血管收缩；而在大鼠中不会出现这种情况。该反应的肺部特异性和种间差异表明，绵羊肺血管内巨噬细胞可能被肝素-鱼精蛋白复合物激活，从而释放血栓素并引发急性肺血管收缩。
