Moore R M, Muir W W, Bertone A L, Oliver J L
Department of Veterinary Clinical Sciences, Ohio State University, Columbus, USA.
Vet Surg. 1998 Jan-Feb;27(1):37-48. doi: 10.1111/j.1532-950x.1998.tb00096.x.
To determine the effect of platelet-activating factor (PAF) antagonist L-691,880 on low-flow ischemia and reperfusion (I-R) of the large colon in horses.
12 adult horses.
Horses were anesthetized, and the large colon was exteriorized through a ventral median celiotomy and instrumented. Colonic arterial blood flow was reduced to 20% of baseline (BL) and maintained for 3 hours; flow was then restored, and the colon was reperfused for 3 hours. One of two solutions was administered intravenously 30 minutes before reperfusion: group 1, 10 mL/kg 0.9% NaCl; and group 2, 5 mg/kg PAF antagonist L-691,880 in 0.9% NaCl. Hemodynamic variables were monitored and recorded at 30-minute intervals. Systemic arterial and colonic venous blood were collected for measurement of blood gas tensions, oximetry analyses, packed cell volume, and total plasma protein concentrations. Colonic venous blood was collected for determination of lactate, 6-keto prostaglandin F1 alpha (6-kPG), prostaglandin E2 (PGE2), and thromboxane B2 (TXB2) concentrations. Full-thickness biopsy specimens were harvested from the left ventral colon for histological evaluation.
There were no significant differences between the two groups for any hemodynamic or metabolic variables. Colonic venous pH decreased, and carbon dioxide tension and lactate concentration increased during ischemia but returned to BL values during reperfusion. Colonic venous 6-kPG concentration was significantly increased above BL value at 2 hours and remained increased through 6 hours in horses of both groups. Colonic venous PGE2 concentration was significantly greater in group 2 compared with group 1 throughout the study. Colonic venous PGE2 concentration was increased above BL value from 3 to 6 hours in horses of both groups. Colonic venous TXB2 concentration was not different between groups but was significantly increased above the BL value for the first hour of reperfusion. Low-flow I-R of the large colon caused significant mucosal necrosis, hemorrhage, edema, and neutrophil infiltration; however, there were no differences in histological variables between vehicle-control and PAF antagonist-treated horses.
No protective effects of PAF antagonist L-691,880 were observed on colonic mucosa associated with low-flow I-R. Additionally, deleterious drug-induced effects on hemodynamic and metabolic variables and colonic mucosal injury were not observed.
确定血小板活化因子（PAF）拮抗剂L-691,880对马的大结肠低流量缺血再灌注（I-R）的影响。
12匹成年马。
对马实施麻醉，通过腹正中剖腹术将大结肠外置并进行仪器监测。结肠动脉血流量降至基线（BL）的20%并维持3小时；然后恢复血流，使结肠再灌注3小时。在再灌注前30分钟静脉注射两种溶液之一：第1组，10 mL/kg 0.9%氯化钠；第2组，5 mg/kg PAF拮抗剂L-691,880溶于0.9%氯化钠中。每隔30分钟监测并记录血流动力学变量。采集全身动脉血和结肠静脉血，用于测定血气张力、血氧饱和度分析、红细胞压积和总血浆蛋白浓度。采集结肠静脉血，用于测定乳酸、6-酮前列腺素F1α（6-kPG）、前列腺素E2（PGE2）和血栓素B2（TXB2）浓度。从左腹侧结肠采集全层活检标本进行组织学评估。
两组在任何血流动力学或代谢变量方面均无显著差异。缺血期间结肠静脉pH值降低，二氧化碳张力和乳酸浓度升高，但在再灌注期间恢复至BL值。两组马在2小时时结肠静脉6-kPG浓度均显著高于BL值，并在6小时内持续升高。在整个研究过程中，第2组结肠静脉PGE2浓度显著高于第1组。两组马在3至6小时时结肠静脉PGE2浓度均高于BL值。两组之间结肠静脉TXB2浓度无差异，但在再灌注的第1小时显著高于BL值。大结肠低流量I-R导致显著的黏膜坏死、出血、水肿和中性粒细胞浸润；然而，在载体对照组和PAF拮抗剂治疗组的马之间，组织学变量没有差异。
未观察到PAF拮抗剂L-691,880对与低流量I-R相关的结肠黏膜有保护作用。此外，未观察到药物对血流动力学和代谢变量以及结肠黏膜损伤的有害影响。
