Montalescot G, Lowenstein E, Ogletree M L, Greene E M, Robinson D R, Hartl K, Zapol W M
Department of Anesthesia, Massachusetts General Hospital, Boston 02114.
Circulation. 1990 Nov;82(5):1765-77. doi: 10.1161/01.cir.82.5.1765.
We used competitive thromboxane A2-prostaglandin endoperoxide receptor blockade (SQ 30,741) as a probe to evaluate the role of thromboxane in ovine pulmonary vasoconstriction associated with protamine reversal of heparin anticoagulation. Control heparin-protamine reactions induced rapid release of thromboxane into arterial plasma (more than 1 ng/ml plasma), a 2.5-fold increase of pulmonary artery pressure, a 20% decrease of PaO2, and a 30% reduction in arterial white blood cell concentration. After giving SQ 30,741 despite similar thromboxane release into arterial plasma after heparin-protamine challenge, acute pulmonary hypertension was significantly reduced when 94% of pulmonary vascular smooth muscle thromboxane receptors were occupied with SQ 30,741 (p less than 0.01 at 1 minute after protamine versus control heparin-protamine reaction) and was completely abolished by a 10 mg/kg i.v. bolus (p less than 0.0001 at 1 minute after protamine versus control). Peripheral leukopenia was not affected by SQ 30,741 prophylaxis, but hypoxemia was prevented. We conclude that thromboxane causes pulmonary vasoconstriction in ovine heparin-protamine-induced pulmonary hypertension. Pulmonary vasoconstriction and hypoxemia can be completely prevented by thromboxane receptor blockade.
我们使用竞争性血栓素A2 - 前列腺素内过氧化物受体阻滞剂（SQ 30,741）作为探针，来评估血栓素在与鱼精蛋白逆转肝素抗凝相关的羊肺动脉收缩中的作用。对照肝素 - 鱼精蛋白反应导致血栓素迅速释放到动脉血浆中（血浆浓度超过1 ng/ml），肺动脉压升高2.5倍，动脉血氧分压（PaO2）降低20%，动脉白细胞浓度降低30%。给予SQ 30,741后，尽管在肝素 - 鱼精蛋白激发后动脉血浆中血栓素释放情况相似，但当94%的肺血管平滑肌血栓素受体被SQ 30,741占据时，急性肺动脉高压显著降低（与对照肝素 - 鱼精蛋白反应相比，鱼精蛋白注射后1分钟时p < 0.01），并且静脉注射10 mg/kg大剂量药物可使其完全消除（与对照相比，鱼精蛋白注射后1分钟时p < 0.0001）。预防性使用SQ 30,741不影响外周白细胞减少，但可预防低氧血症。我们得出结论，血栓素在羊肝素 - 鱼精蛋白诱导的肺动脉高压中导致肺血管收缩。血栓素受体阻断可完全预防肺血管收缩和低氧血症。
