Laesser M, Fändriks L, Pettersson A, Ewert S, Aneman A
Department of Physiology, Göteborg University, Sweden.
Shock. 2000 Oct;14(4):471-7. doi: 10.1097/00024382-200014040-00009.
Angiotensin II (AngII) is an important vasoconstrictor during hypovolemia. This study focused on the effects of the AngII receptor blocker candesartan on intestinal, hepatic, and renal hemodynamics during severe hypovolemia when administered in preexisting moderate hypovolemia. It was hypothesized that specific AngII receptor blockade might enhance splanchnic perfusion during hypovolemia. Fasted, anesthetized, ventilated, juvenile pigs were hemorrhaged by 20% of the blood volume for 30 min. Animals were then randomized to receive candesartan (CAND, n = 11) or the vehicle (CTRL, n = 10) prior to further hemorrhage to 40% of the blood volume for 30 min. The shed blood was then retransfused. Systemic and splanchnic hemodynamics were recorded including intestinal mucosal, superficial and parenchymal hepatic, and cortical and medullary renal microcirculation by laser-Doppler flowmetry. Arterial blood gases were analysed. Candesartan-treated animals maintained mesenteric and jejunal mucosal perfusion during 40% hypovolemia compared to CTRL animals, while no differences were observed in the hepatic and renal circulation. Retransfusion restored mesenteric and renal blood flows despite persistent hypotension and reduced cardiac output in both CAND and CTRL animals. Renal medullary and hepatic parenchymal microcirculation failed to recover during retransfusion in both CAND and CTRL animals. Arterial acidosis, hypercarbia, and a negative base excess were observed in CTRL animals following retransfusion whereas those parameters were normalised in CAND animals. Administration of candesartan in moderate hypovolemia ameliorated the reduction and consequences of mesenteric and intestinal, but not hepatic perfusion during severe hypovolemia. No adverse effects were observed in the renal circulation.
血管紧张素II（AngII）是低血容量时一种重要的血管收缩剂。本研究聚焦于血管紧张素II受体阻滞剂坎地沙坦在严重低血容量时（预先存在中度低血容量情况下给药）对肠道、肝脏和肾脏血流动力学的影响。研究假设是，特异性血管紧张素II受体阻断可能会在低血容量时增强内脏灌注。将禁食、麻醉、通气的幼年猪放血，放血量为血容量的20%，持续30分钟。然后，在进一步放血至血容量的40%并持续30分钟之前，将动物随机分为接受坎地沙坦（CAND，n = 11）或赋形剂（CTRL，n = 10）组。随后将放出的血液回输。通过激光多普勒血流仪记录全身和内脏血流动力学，包括肠黏膜、肝脏浅层和实质、以及肾皮质和髓质微循环。分析动脉血气。与对照组动物相比，坎地沙坦治疗的动物在低血容量40%时维持了肠系膜和空肠黏膜灌注，而在肝脏和肾脏循环方面未观察到差异。尽管坎地沙坦组和对照组动物均持续存在低血压且心输出量降低，但回输恢复了肠系膜和肾脏血流。在坎地沙坦组和对照组动物回输过程中，肾髓质和肝脏实质微循环均未恢复。对照组动物回输后出现动脉酸中毒、高碳酸血症和碱剩余负值，而这些参数在坎地沙坦组动物中恢复正常。在中度低血容量时给予坎地沙坦可改善严重低血容量时肠系膜和肠道灌注的减少及其后果，但对肝脏灌注无改善作用。在肾脏循环中未观察到不良反应。
