Anner H, Kaufman R P, Kobzik L, Valeri C R, Shepro D, Hechtman H B
Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115.
Ann Surg. 1987 Nov;206(5):642-8. doi: 10.1097/00000658-198711000-00015.
Ischemia stimulates thromboxane (Tx) synthesis. This study tests the hypothesis that the cardiopulmonary dysfunction that may follow aortic declamping is related to Tx. Anesthetized dogs (N = 15) were subjected to 4 hours of infrarenal aortic cross-clamping. In untreated control animals (N = 7), plasma levels of TxB2 rose from 654 +/- 74 pg/mL to 1238 +/- 585 pg/mL at 5 min (p less than 0.05), and to 3174 +/- 912 pg/mL 3 hours after declamping (p less than 0.05). Mean pulmonary artery pressure (MPAP) rose 5 min after declamping from 13 +/- 2 mmHg to 21 +/- 2 mmHg (p less than 0.05). Cardiac Index (CI) declined during ischemia from 181 +/- 30 mL/kg.min to 128 +/- 16 mL/min.kg (p less than 0.05), and to 80 +/- 8 mL/min.kg after 4 hours of reperfusion (p less than 0.05). Platelet counts declined but platelets labeled with In 111 did not accumulate in the lungs, whereas quantitative counts of polymorphonuclear leukocytes (PMN) in the lungs 4 hours after declamping yielded 213 +/- 33 PMN/25 high power fields (HPF) in dependent areas of the lung and 153 +/- 26 PMN/25 HPF in nondependent areas. The wet/dry weight ratio of the lungs was not elevated, although foci of proteinaceous exudate and PMNs in alveoli were noted. Another group of dogs (N = 8) were pretreated by random choice with the Tx synthase inhibitor OKY-046 2 mg/kg IV every 2 hours, which led to: lower TxB2 levels at baseline 95 +/- 35 pg/mL (p less than 0.05), 5 min after ischemia 140 +/- 93 pg/mL and after 3 hours of reperfusion 122 +/- 36 (p less than 0.05); lower MPAP, 16 +/- 2 mmHg (p less than 0.05); higher CI throughout (p less than 0.05); normal histology and reduced pulmonary PMN sequestration both in dependent 127 +/- 15 PMN/25 HPF and nondependent areas of the lungs 95 +/- 11 PMN/25 HPF (p less than 0.05). In animals undergoing sham ischemia (N = 3), levels of TxB2 and cardiopulmonary function remained unchanged from baseline. There were 150 PMN/25 HPF in dependent and 85 PMN/25 HPF in nondependent lung areas. The results indicate that ischemia-generated Tx mediates a rise in MPAP, a fall in CI, and PMN entrapment in the lungs.
缺血会刺激血栓素（Tx）的合成。本研究检验了以下假说：主动脉夹闭后可能出现的心肺功能障碍与Tx有关。对15只麻醉犬进行了4小时的肾下腹主动脉交叉夹闭。在未治疗的对照动物（n = 7）中，血浆TxB2水平在夹闭后5分钟从654±74 pg/mL升至1238±585 pg/mL（p<0.05），夹闭解除后3小时升至3174±912 pg/mL（p<0.05）。平均肺动脉压（MPAP）在夹闭解除后5分钟从13±2 mmHg升至21±2 mmHg（p<0.05）。心脏指数（CI）在缺血期间从181±30 mL/kg·min降至128±16 mL/min·kg（p<0.05），再灌注4小时后降至80±8 mL/min·kg（p<0.05）。血小板计数下降，但用铟111标记的血小板未在肺中聚集，而夹闭解除后4小时肺中多形核白细胞（PMN）的定量计数在肺的下垂部位为213±33个PMN/25高倍视野（HPF），非下垂部位为153±26个PMN/25 HPF。肺的湿/干重比未升高，尽管在肺泡中观察到了蛋白质渗出灶和PMN。另一组犬（n = 8）随机选择每2小时静脉注射Tx合酶抑制剂OKY - 046 2 mg/kg进行预处理，结果导致：基线时TxB2水平较低，为95±35 pg/mL（p<0.05），缺血后5分钟为140±93 pg/mL，再灌注3小时后为122±36 pg/mL（p<0.05）；MPAP较低，为16±2 mmHg（p<0.05）；整个过程中CI较高（p<0.05）；组织学正常，肺中PMN隔离减少，下垂部位为127±15个PMN/25 HPF，非下垂部位为95±11个PMN/25 HPF（p<0.05）。在进行假缺血的动物（n = 3）中，TxB2水平和心肺功能与基线相比保持不变。下垂肺区有150个PMN/25 HPF，非下垂肺区有85个PMN/25 HPF。结果表明，缺血产生的Tx介导了MPAP升高、CI降低以及PMN在肺中的滞留。
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