Huang Hui-Chun, Wang Sun-Sang, Chen Yi-Chou, Lee Fa-Yauh, Chang Full-Young, Lin Han-Chieh, Hou Ming-Chih, Chang Ching-Chih, Lee Shou-Dong
Division of Gastroenterology, Taipei Veterans General Hospital, Taipei, Taiwan, Republic of China.
Scand J Gastroenterol. 2006 Dec;41(12):1440-5. doi: 10.1080/00365520600735696.
Collateral vascular responsiveness to vasoconstrictors may be crucial in the management of acute variceal bleeding. In an in situ perfusion model, arginine vasopressin (AVP) has been shown to cause a direct vasoconstrictive effect on portal-systemic collaterals and this effect is enhanced by preincubation of indomethacin (INDO). The purpose of this study was to investigate the effects of chronic INDO administration on the portal-systemic collateral responsiveness to AVP and the degree of portal-systemic shunting in portal hypertensive rats.
Rats with partial portal vein ligation randomly received daily subcutaneous injections with INDO (5 mg/kg) or distilled water (control group) 2 days prior to until 7 days after ligation. Systemic and portal hemodynamics was evaluated on the 8th day. Using an in situ collateral perfusion model, AVP (10(-10)-10(-7) M) at a constant flow rate (20 ml/min) was applied. In another series, Krebs solution with different flow rates (5-30 ml/min) was used to obtain flow-pressure curves: the slopes represent collateral vascular resistances--the higher resistances indicate fewer collaterals.
Mean arterial pressure and portal pressure were not significantly different between the INDO-treated group and the control group (p>0.05). In the first series of experiments, INDO treatment increased the collateral perfusion pressure to AVP at 10(-8) M, 3x10(-8) M, and 10(-7) M (p<0.05). In the second series, INDO did not change collateral vascular resistance, which suggests that the degree of shunting was not altered.
Chronic INDO treatment improves the collateral vascular responsiveness to AVP without ameliorating portal-systemic shunting in portal hypertensive rats.
侧支血管对血管收缩剂的反应性在急性静脉曲张出血的治疗中可能至关重要。在原位灌注模型中，已证明精氨酸加压素（AVP）对门体侧支血管有直接的血管收缩作用，且吲哚美辛（INDO）预孵育可增强这种作用。本研究的目的是探讨长期给予INDO对门静脉高压大鼠门体侧支血管对AVP的反应性及门体分流程度的影响。
部分门静脉结扎的大鼠在结扎前2天直至结扎后7天，随机每日皮下注射INDO（5mg/kg）或蒸馏水（对照组）。在第8天评估全身和门静脉血流动力学。使用原位侧支灌注模型，以恒定流速（20ml/min）应用AVP（10⁻¹⁰ - 10⁻⁷M）。在另一组实验中，使用不同流速（5 - 30ml/min）的 Krebs 溶液获得流量-压力曲线：斜率代表侧支血管阻力——阻力越高表明侧支越少。
INDO治疗组与对照组之间的平均动脉压和门静脉压无显著差异（p>0.05）。在第一系列实验中，INDO治疗使10⁻⁸M、3×10⁻⁸M和10⁻⁷M的AVP引起的侧支灌注压升高（p<0.05）。在第二系列实验中，INDO未改变侧支血管阻力，这表明分流程度未改变。
长期INDO治疗可改善门静脉高压大鼠侧支血管对AVP的反应性，但不会改善门体分流。
