Soulsby M E, Jacobs E R, Perlmutter B H, Bone R C
Prostaglandins Leukot Med. 1984 Mar;13(3):295-305. doi: 10.1016/0262-1746(84)90043-x.
We have concluded that Ibuprofen, a cyclooxygenase inhibitor with high specificity for the preferential blockage of thromboxane synthetase, significantly improves arterial blood pressure, cardiac index, and arterial pH during endotoxin shock in dogs (J. Clin. Invest. 70:536, 1982). This study was undertaken to determine whether Ibuprofen (25 mg/kg i.v.) administered 20 min prior to endotoxin (2 mg/kg i.v.) is able to overcome the depressed ability of cardiac microsomes to actively sequester calcium after 2 hrs of endotoxin shock. Results indicate that microsomes isolated from hearts of animals pretreated with Ibuprofen and then given endotoxin are able to sequester calcium at rates similar to microsomes isolated from control hearts. Microsomes isolated from hearts of animals in endotoxin shock without Ibuprofen show the anticipated depression of calcium sequestering ability. The improved ability of microsomes from the hearts of animals pretreated with Ibuprofen to sequester calcium is the result of normal Ca+2-Mg+2 ATPase activity in the microsomal membrane. We conclude that Ibuprofen protects against the detrimental hemodynamic derangements of endotoxin induced shock in the dog, and thereby also improves cardiac subcellular calcium transport; the factor regulating contractility. Ibuprofen may warrant evaluation as a protective agent to be used prophylactically in high risk cases of endotoxemia.
我们得出结论，布洛芬是一种对血栓素合成酶的优先阻断具有高特异性的环氧化酶抑制剂，在犬内毒素休克期间能显著改善动脉血压、心脏指数和动脉pH值（《临床研究杂志》70:536，1982年）。本研究旨在确定在内毒素（静脉注射2mg/kg）前20分钟静脉注射布洛芬（25mg/kg）是否能够克服内毒素休克2小时后心脏微粒体主动摄取钙的能力下降。结果表明，从预先用布洛芬处理然后给予内毒素的动物心脏中分离出的微粒体摄取钙的速率与从对照心脏中分离出的微粒体相似。从未用布洛芬的内毒素休克动物心脏中分离出的微粒体显示出预期的钙摄取能力下降。预先用布洛芬处理的动物心脏微粒体摄取钙能力的提高是微粒体膜中正常的Ca+2-Mg+2 ATP酶活性的结果。我们得出结论，布洛芬可预防犬内毒素诱导休克的有害血流动力学紊乱，从而也改善心脏亚细胞钙转运；钙转运是调节收缩性的因素。布洛芬可能值得作为一种保护剂进行评估，用于内毒素血症高危病例的预防性治疗。
