Byrne K, Sielaff T D, Carey P D, Tatum J L, Blocher C R, Vasquez A, Hirsh J I, Sugerman H J
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23229.
Circ Shock. 1990 Feb;30(2):117-27.
The effects of two pharmacologically distinct histamine H2 receptor antagonists were studied in combination with ibuprofen (I) and diphenhydramine (D) in a porcine model of septic ARDS. Cimetidine (C) is reported as having direct oxygen radical scavenging abilities and is an inhibitor of cytochrome P-450, whereas ranitidine (R) acts solely by H2 receptor blockade. Four groups were studied: Group Ps (n = 8) received a continuous infusion of live Pseudomonas aeruginosa 5 x 10(8) CFU/ml at 0.3 ml/20kg/min, Group C (n = 6) received a control saline infusion, and the treatment groups received I (12.5 mg/kg) and D (10 mg/kg) in combination with either C (150 mg, CID, n = 6) or R (25 mg, RID, n = 5) given at 20 and 120 minutes after the onset of Ps. Pulmonary (PAP) and systemic (SAP) arterial pressures, cardiac index (CI), PaO2, thermal cardiogreen extravascular lung water (EVLW) and scintigraphically determined pulmonary albumin flux (slope index, SI) were measured. Ps infusion produced significant (p less than 0.05) cardiovascular collapse, hypoxemia and increased EVLW and SI. Both CID and RID temporarily reversed pulmonary arterial hypertension and maintained PaO2, EVLW, SAP and CI at control levels throughout the study, and significantly improved SI at 180 min. These results suggest that cimetidine and ranitidine act in this combination therapy primarily as H2 receptor antagonists.
在脓毒症急性呼吸窘迫综合征（ARDS）的猪模型中，研究了两种药理作用不同的组胺H2受体拮抗剂与布洛芬（I）和苯海拉明（D）联合使用的效果。据报道，西咪替丁（C）具有直接清除氧自由基的能力，并且是细胞色素P - 450的抑制剂，而雷尼替丁（R）仅通过H2受体阻断发挥作用。研究了四组：Ps组（n = 8）以0.3 ml/20kg/min的速度持续输注浓度为5 x 10(8) CFU/ml的活铜绿假单胞菌，C组（n = 6）接受对照生理盐水输注，治疗组在Ps开始后20分钟和120分钟接受I（12.5 mg/kg）和D（10 mg/kg），并分别联合C（150 mg，CID，n = 6）或R（25 mg，RID，n = 5）。测量了肺动脉（PAP）和体动脉（SAP）压、心脏指数（CI）、动脉血氧分压（PaO2）、热稀释法测定的心绿素血管外肺水（EVLW）以及闪烁扫描法测定的肺白蛋白通量（斜率指数，SI）。输注Ps导致显著（p < 0.05）的心血管衰竭、低氧血症以及EVLW和SI增加。在整个研究过程中，CID组和RID组均暂时逆转了肺动脉高压，并使PaO2、EVLW、SAP和CI维持在对照水平，且在180分钟时显著改善了SI。这些结果表明，西咪替丁和雷尼替丁在这种联合治疗中主要作为H2受体拮抗剂发挥作用。
