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


METHODS
Prospective, randomized, controlled experimental study.


METHODS
University-affiliated animal research laboratory.


METHODS
Fasted, anesthetized, ventilated, juvenile domestic pigs of both sexes.


METHODS
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).


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.
Aneman
A
A
Department of Anesthesiology and Intensive Care, Göteborg University, Sweden.
Svensson
M
M
Broomé
M
M
Biber
B
B
Petterson
A
A
Fändriks
L
L
D000136:Acid-Base Equilibrium / Q000187:drug effects; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D020896:Hypovolemia / Q000188:drug therapy*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects; D016014:Linear Models; D008297:Male; D011446:Prospective Studies; D011897:Random Allocation; D012084:Renin-Angiotensin System / Q000187:drug effects; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan