Nowicki P T
Department of Pediatrics, The Ohio State University, Columbus 43210; and Wexner Institute for Pediatric Research, Childrens Hospital, Columbus, Ohio 43205, USA.
Am J Physiol. 1998 Oct;275(4):G758-68. doi: 10.1152/ajpgi.1998.275.4.G758.
Studies were conducted to determine the effect of mechanically induced sustained flow reduction on intestinal hemodynamics and oxygenation in 3- and 35-day-old swine. In vitro gut loops were perfused under controlled-pressure conditions from an oxygenated blood reservoir at age-appropriate perfusion pressures; pressure was rapidly reduced to a level that lowered flow rate to approximately 50% of its baseline value, and pressure was then kept at that level for 2 h. In 3-day-old intestine, vascular resistance (Ri) increased by 20% immediately after pressure and flow reduction but then stabilized for 3-4 min; thereafter, flow began to decrease despite maintenance of perfusion pressure, so that Ri increased an additional 15% by 30 min after flow reduction. Flow continued to diminish over the next 90 min, though at much slower rate. Intestine from 35-day-old swine demonstrated an immediate increase in Ri after pressure and flow reduction, but thereafter Ri increased very little. The protocol was repeated within in vitro gut loops perfused under controlled-flow conditions, and within autoperfused, innervated gut loops developed in vivo and similar observations were made in both preparations. In 3-day-old intestine, pretreatment with the L-arginine analog Nomega-monomethyl-L-arginine (10(-4) M) had no effect on the immediate rise in resistance occurring in the first 1 min but substantially attenuated the subsequent slow, progressive rise noted thereafter. Pretreatment with the angiotensin 1A receptor antagonist losartan (2 x 10(-6) M) had no effect on hemodynamic changes during the first 60 min after mechanical perfusion pressure reduction but attenuated the very slight increase in resistance noted during the final 60 min of the protocol. The postnatal intestinal circulation demonstrates progressive vasoconstriction when its flow rate is mechanically reduced in a sustained manner, and this effect is age specific, occurring in 3- but not 35-day-old swine. These changes in gut vascular resistance may be consequent to loss of nitric oxide production and/or local production of angiotensin.
开展了多项研究，以确定机械诱导的持续血流减少对3日龄和35日龄猪肠道血流动力学和氧合作用的影响。在体外，将肠袢在适宜年龄的灌注压力下，从充氧血库进行控压灌注；压力迅速降至使流速降低至其基线值约50%的水平，然后将压力维持在该水平2小时。在3日龄的肠道中，压力和血流降低后，血管阻力（Ri）立即增加20%，但随后稳定3 - 4分钟；此后，尽管维持灌注压力，血流仍开始下降，因此在血流降低后30分钟时，Ri又额外增加了15%。在接下来的90分钟内，血流持续减少，不过速度要慢得多。35日龄猪的肠道在压力和血流降低后，Ri立即增加，但此后Ri增加很少。该方案在控流条件下灌注的体外肠袢以及体内构建的自灌注、有神经支配的肠袢中重复进行，在两种制剂中均观察到类似结果。在3日龄的肠道中，用L - 精氨酸类似物N - 甲基 - L - 精氨酸（10⁻⁴ M）预处理对最初1分钟内出现的阻力立即升高没有影响，但显著减弱了此后观察到的随后缓慢、渐进性的升高。用血管紧张素1A受体拮抗剂氯沙坦（2×10⁻⁶ M）预处理在机械灌注压力降低后的最初60分钟内对血流动力学变化没有影响，但减弱了该方案最后60分钟内观察到的非常轻微的阻力增加。当以持续方式机械性降低其流速时，新生仔猪肠道循环表现出进行性血管收缩，且这种效应具有年龄特异性，发生在3日龄而非35日龄的猪中。肠道血管阻力的这些变化可能是一氧化氮生成减少和/或血管紧张素局部生成的结果。
