Ridings P C, Windsor A C, Sugerman H J, Kennedy E, Sholley M M, Blocher C R, Fisher B J, Fowler A A
Department of Surgery, Medical College of Virginia, Richmond.
Arch Surg. 1994 Nov;129(11):1144-52. doi: 10.1001/archsurg.1994.01420350042004.
To determine the effects of pretreatment and posttreatment with pentoxifylline in a porcine model of gram-negative sepsis.
Nonrandomized controlled trial.
Young Yorkshire swine.
Six groups of ventilated swine were studied for 5 hours. Group 1 swine (control, n = 8) received saline solution only. Group 2 swine (sepsis, n = 8) received a 1-hour infusion of Pseudomonas aeruginosa. Groups 3, 4, and 5 swine received the P aeruginosa infusion and a 20 mg/kg bolus followed by a 6 mg/kg per hour infusion of pentoxifylline. Group 3 swine (n = 6) received pentoxifylline prior to the onset of sepsis; group 4 swine (n = 6) received pentoxifylline at 1 hour and group 5 swine (n = 4) at 2 hours after the onset of the P aeruginosa infusion. Group 6 swine (control pentoxifylline, n = 3) received pentoxifylline only.
Hemodynamic variables, neutrophil counts and CD18 expression, tumor necrosis factor activity, and arterial blood gases were measured hourly. Bronchoalveolar lavage was performed at 0 and 5 hours to measure neutrophil and protein content.
All variables remained unchanged in the control and control pentoxifylline groups. Both pretreatment and posttreatment with pentoxifylline significantly attenuated lung injury and improved arterial PaO2. The cardiac index was significantly improved by administration of pentoxifylline in groups 3 and 4. Administration of pentoxifylline to group 5 animals in established septic shock caused uncontrolled, fatal systemic hypotension in two of the four animals. Plasma tumor necrosis factor activity, blood polymorphonuclear leukocyte counts, and CD18 expression were unaffected by the administration of pentoxifylline.
Pentoxifylline protects against pulmonary and systemic hemodynamic derangements in fulminant sepsis and protects against pulmonary dysfunction. Pentoxifylline has a "therapeutic window" when given in established sepsis; if administration is delayed until overt septic shock occurs, it may then have deleterious effects.
在革兰氏阴性菌败血症猪模型中确定己酮可可碱预处理和后处理的效果。
非随机对照试验。
年轻的约克夏猪。
对六组通气猪进行5小时的研究。第1组猪（对照组，n = 8）仅接受生理盐水。第2组猪（败血症组，n = 8）接受1小时的铜绿假单胞菌输注。第3、4和5组猪接受铜绿假单胞菌输注以及20mg/kg的静脉推注，随后以6mg/kg每小时的速度输注己酮可可碱。第3组猪（n = 6）在败血症发作前接受己酮可可碱；第4组猪（n = 6）在铜绿假单胞菌输注后1小时接受己酮可可碱，第5组猪（n = 4）在输注后2小时接受己酮可可碱。第6组猪（己酮可可碱对照组，n = 3）仅接受己酮可可碱。
每小时测量血流动力学变量、中性粒细胞计数和CD18表达、肿瘤坏死因子活性及动脉血气。在0小时和5小时进行支气管肺泡灌洗以测量中性粒细胞和蛋白质含量。
对照组和己酮可可碱对照组的所有变量均保持不变。己酮可可碱预处理和后处理均显著减轻肺损伤并改善动脉血氧分压。第3组和第4组中，己酮可可碱给药显著改善心脏指数。在已发生感染性休克的第5组动物中给予己酮可可碱，导致4只动物中有2只出现无法控制的致命性全身性低血压。血浆肿瘤坏死因子活性、血液多形核白细胞计数和CD18表达不受己酮可可碱给药的影响。
己酮可可碱可预防暴发性败血症中的肺和全身血流动力学紊乱，并预防肺功能障碍。在已发生的败血症中给予己酮可可碱有一个“治疗窗”；如果给药延迟至明显的感染性休克发生，则可能产生有害作用。
