Specific angiotensin II receptor blockade improves intestinal perfusion during graded hypovolemia in pigs

Anders Åneman*, Mats Svensson, Mikael Broomé, Björn Biber, Anders Petterson, Lars Fändriks

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Objective: To investigate the potential of specific angiotensin II subtype 1 (AT1) receptor blockade to modify the mesenteric hemodynamic response to acute hypovolemia and retransfusion. Design: Prospective, randomized, controlled experimental study. Setting: University-affiliated animal research laboratory. Subjects: Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes. Interventions: 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). Measurements and Main Results: 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. Conclusions: 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.

Original languageEnglish
Pages (from-to)818-823
Number of pages6
JournalCritical Care Medicine
Issue number3
Publication statusPublished - 2000


  • Angiotensin II
  • Hemorrhage
  • Intestinal circulation
  • Receptor blockade
  • Renin-angiotensin system


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