Carter M B, Wilson M A, Wead W B, Garrison R N
Department of Surgery, School of Medicine, University of Louisville, Ky, USA.
Arch Surg. 1995 Dec;130(12):1337-44. doi: 10.1001/archsurg.1995.01430120091014.
To assess the effects of pentoxifylline posttreatment on hemodynamic variables and acute pulmonary injury in the rat intestinal ischemia-reperfusion (I-R) model, using a recently developed method of fluorescent intravital pulmonary videomicroscopy.
Anesthetized male Sprague-Dawley rats were cannulated for measurement of mean arterial pressure, heart rate, cardiac output, arterial blood gas values, and hematocrit. Rats underwent isolation of the superior mesenteric artery for intestinal I-R (45 minutes of ischemia, 120 minutes of reperfusion) and right lateral thoracotomy for pulmonary videomicroscopy. Epi-illumination fluorescent videomicroscopy was used to quantitate leakage of intravascular fluorescently labeled albumin into alveoli, while hemodynamic variables were simultaneously recorded. In the treatment groups, pentoxifylline was administered after 30 minutes of intestinal ischemia. Data (mean +/- SEM) were recorded before and during intestinal ischemia and after reperfusion at 30-minute intervals.
The appearance of fluorescently labeled albumin into alveolar airspaces was quantitated off-line by computer and reported as the alveolar leak index.
Intestinal I-R caused alveolar macromolecular leakage, marked by a 300% +/- 48% increase from baseline (P < .05) in the alveolar leak index. Intestinal I-R also produced systemic hemodynamic instability demonstrated by a decrease in the mean arterial blood pressure (-36% +/- 5% vs baseline, P < .05) and cardiac output (-42% +/- 6% vs baseline, P < .05), metabolic acidosis (final arterial pH of 7.17, P < .05 vs initial pH), and a 2.3-fold increase in the intravenous fluid requirement when compared with that in sham animals (P < .05). Treatment with pentoxifylline 30 minutes after intestinal ischemia attenuated pulmonary macromolecular leakage (P < .05 vs nontreated I-R) and reduced the decrease in cardiac output (-15% +/- 7% vs baseline, not statistically significant). Pentoxifylline treatment had no effect on the mean arterial blood pressure, heart rate, metabolic acidosis, or intravenous fluid requirement.
Pentoxifylline reduces alveolar capillary membrane injury and subsequent protein leakage and improves cardiac output when administered after 30 minutes of intestinal ischemia. These data suggest that pentoxifylline may be a possible candidate as a future therapy for acute pulmonary dysfunction. Further studies in human patients are necessary.
采用最近开发的荧光活体肺视频显微镜方法，评估己酮可可碱治疗对大鼠肠缺血再灌注（I-R）模型中血流动力学变量和急性肺损伤的影响。
对麻醉的雄性Sprague-Dawley大鼠进行插管，以测量平均动脉压、心率、心输出量、动脉血气值和血细胞比容。大鼠接受肠系膜上动脉分离以进行肠I-R（缺血45分钟，再灌注120分钟），并进行右外侧开胸以进行肺视频显微镜检查。落射荧光视频显微镜用于定量血管内荧光标记白蛋白向肺泡的渗漏，同时记录血流动力学变量。在治疗组中，肠缺血30分钟后给予己酮可可碱。在肠缺血前、缺血期间以及再灌注后每隔30分钟记录数据（均值±标准误）。
通过计算机离线定量荧光标记白蛋白在肺泡气腔中的出现情况，并报告为肺泡渗漏指数。
肠I-R导致肺泡大分子渗漏，表现为肺泡渗漏指数较基线增加300%±48%（P<0.05）。肠I-R还导致全身血流动力学不稳定，表现为平均动脉血压降低（-36%±5%对比基线，P<0.05）和心输出量降低（-42%±6%对比基线，P<0.05）、代谢性酸中毒（最终动脉pH值为7.17，与初始pH值相比P<0.05），与假手术动物相比，静脉输液需求量增加2.3倍（P<0.05）。肠缺血30分钟后用己酮可可碱治疗可减轻肺大分子渗漏（与未治疗的I-R相比P<0.05），并减少心输出量的降低（-15%±7%对比基线，无统计学意义）。己酮可可碱治疗对平均动脉血压、心率、代谢性酸中毒或静脉输液需求量无影响。
肠缺血30分钟后给予己酮可可碱可减少肺泡毛细血管膜损伤及随后的蛋白渗漏，并改善心输出量。这些数据表明，己酮可可碱可能是未来治疗急性肺功能障碍的一种可能选择。有必要在人类患者中进行进一步研究。
