Milrinone improves intestinal villus blood flow during endotoxemia.
OBJECTIVE
To determine whether the compromised intestinal villus blood flow in a rat model of endotoxemia could be improved by continuous infusion of the phosphodiesterase (PDE) inhibitor milrinone.


METHODS
Twenty-four anesthetized and ventilated rats were laparotomized and an ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides without phosphodiesterase inhibitor pretreatment (=LPS group); or infusion of LPS with milrinone pretreatment (= milrinone group), or without infusion of LPS or milrinone (=control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = D(A) and mean erythrocyte velocity within the arterioles= V(E)) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from D(A) and V(E).


RESULTS
In the milrinone group MAP decreased 60 min after induction of endotoxemia whereas it remained stable in the control and the LPS group. In both groups given endotoxin V(E) decreased after start of LPS infusion. In contrast, D(A) decreased in the LPS group, but increased in the milrinone group after 120 min of endotoxemia. Thus, the endotoxin-induced decrease of intestinal villus blood flow was diminished but not fully restored by milrinone infusion.


CONCLUSIONS
Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.
Department of Anesthesiology, University of Heidelberg, Germany. werner.schmidt@urz.uni-heidelberg.de
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W
Schmidt
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Tinelli
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Secchi
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Gebhard
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Martin
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Schmidt
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology; D019446:Endotoxemia / Q000503:physiopathology*; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000098:blood supply / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D020105:Milrinone / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D002316:Cardiotonic Agents; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014665:Vasodilator Agents; D020105:Milrinone