Aneman A, Svensson M, Broomé M, Biber B, Petterson A, Fändriks L
Department of Anesthesiology and Intensive Care, Göteborg University, Sweden.
Crit Care Med. 2000 Mar;28(3):818-23. doi: 10.1097/00003246-200003000-00034.
To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion.
Prospective, randomized, controlled experimental study.
University-affiliated animal research laboratory.
Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes.
Acute, graded hypovolemia by 20% and 40% of the total estimated blood volume followed by retransfusion in control animals (CTRL; n = 10) and animals pretreated with the AT1 receptor blocker candesartan (CAND; n = 10).
Invasive monitoring of arterial and central venous blood pressures, cardiac output, portal venous blood flow, and jejunal mucosal blood flow. Blood gases were repeatedly analyzed to calculate oxygen delivery and consumption. Thirty minutes after each level of hypovolemia at 20% and 40%, cardiac output was decreased in CTRL animals from a baseline of 2.9 +/- 0.1 to 1.8 +/- 0.2 and 1.1 +/- 0.2 L/min, with no differences compared with CAND animals. Cardiac output was restored to 3.0 +/- 0.3 L/min 30 mins after retransfusion in CTRL animals, with no significant intergroup differences. Baseline portal venous blood flow (Q(MES)) and jejunal mucosal perfusion (PU(JEJ)) were greater in CAND animals compared with CTRL animals. During graded hypovolemia, CAND animals maintained Q(MES) and PU(JEJ) at significantly higher levels compared with CTRL animals, particularly after 40% hemorrhage (+221% and + 244%, respectively, relative to the mean values in CTRL animals). The same pattern was observed after retransfusion. Moreover, the calculated mesenteric critical oxygen delivery was significantly greater in CTRL animals (74 mL/min) compared with CAND animals (34 mL/min). No animals died in the CAND group, whereas four animals died during 40% hypovolemia or retransfusion in the CTRL group.
Specific AT1 blockade before acute hypovolemia significantly ameliorated mesenteric and, in particular, jejunal mucosal hypoperfusion. In addition, cardiovascular stability was improved, and mortality in conjunction with acute hypovolemia and retransfusion could be completely avoided. These findings support a fundamental role of the renin-angiotensin system in the mesenteric response to acute hypovolemia and indicate a substantial interventional potential for candesartan in conjunction with circulatory stress.
研究特异性血管紧张素II 1型（AT1）受体阻断对急性低血容量和再输血时肠系膜血流动力学反应的影响。
前瞻性、随机、对照实验研究。
大学附属动物研究实验室。
禁食、麻醉、通气的幼年家猪，雌雄不限。
对对照组动物（CTRL；n = 10）和用AT1受体阻滞剂坎地沙坦预处理的动物（CAND；n = 10）进行急性、分级低血容量处理，使血容量减少估计总量的20%和40%，随后进行再输血。
有创监测动脉血压、中心静脉压、心输出量、门静脉血流量和空肠黏膜血流量。反复分析血气以计算氧输送和氧消耗。在20%和40%的每个低血容量水平后30分钟，CTRL组动物的心输出量从基线的2.9±0.1降至1.8±0.2和1.1±0.2 L/min，与CAND组动物相比无差异。CTRL组动物再输血30分钟后心输出量恢复至3.0±0.3 L/min，组间无显著差异。与CTRL组动物相比，CAND组动物的基线门静脉血流量（Q(MES)）和空肠黏膜灌注（PU(JEJ)）更高。在分级低血容量期间，与CTRL组动物相比，CAND组动物的Q(MES)和PU(JEJ)维持在显著更高水平，尤其是在40%出血后（相对于CTRL组动物的平均值分别增加221%和244%）。再输血后观察到相同模式。此外，计算得出的肠系膜临界氧输送在CTRL组动物（74 mL/min）中显著高于CAND组动物（34 mL/min）。CAND组无动物死亡，而CTRL组有4只动物在40%低血容量或再输血期间死亡。
急性低血容量前进行特异性AT1阻断可显著改善肠系膜尤其是空肠黏膜的灌注不足。此外，改善了心血管稳定性，可完全避免急性低血容量和再输血时的死亡。这些发现支持肾素-血管紧张素系统在肠系膜对急性低血容量反应中的重要作用，并表明坎地沙坦在应对循环应激时有很大的干预潜力。
