Milrinone improves intestinal villus blood flow during endotoxemia

Abstract

Purpose: 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. Conclusion:Our results indicate that milrinone has some beneficial microcirculatory effects during endotoxemia. Although it contributed to systemic hypotension, it attenuated intestinal mucosal hypoperfusion.Objectif : Déterminer si le flot sanguin intestinal dont les grandes fonctions sont altérées dans un modèle d'endotoxémie chez le rat peut être amélioré par une perfusion continue d'un inhibiteur de la phosphodiestérase (PDE), la milrinone.Méthode : Vingt-quatre rats sous anesthésie et ventilation ont été laparotomisés et une portion iléale a été extériorisée et ouverte par une incision antimésentérique. Le segment iléal a été fixé par la surface muqueuse extériorisée. Les paramètres microcirculatoires ont été évalués par vidéomicroscopie vitale. Les animaux ont été assignés à l'un des trois groupes de traitements : une perfusion de lipopolysaccharides d'Escherichia coli sans pré-traitement avec l'inhibiteur de la phosphodiestérase (groupe LPS), ou une perfusion de LPS avec un prétraitement à la milrinone (groupe milrinone), ou sans perfusion de LPS ou de milrinone (groupe témoin). Les paramètres macrohémodynamiques (TAM, FC) et microhémodynamiques de la muqueuse iléale (diamètre moyen des artéri-oles centrales D A et vélocité moyenne des érythrocytes dans les artérioles V E ) ont été mesurés 30 min avant l'induction de l'endotoxémie et à 0, 60 et 120 min après. Le flot sanguin des villosités muqueuses a été calculé à partir de D A et de V E .Résultats...

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“…[46,47] Although it improves cardiac performance in these patients, it is not recommended for the treatment of sepsis because of its vasodilator effect. [48] However, the anti-inflammatory effects of milrinone, as well as cardiovascular effects, have been shown. [49,50] Ming Gong et al [51] to investigate the effect of milrinone on cardiopulmonary bypass associated inflammation, randomized 30 patients before cardiopulmonary bypass by inhalation of milrinone and saline.…”

Effects of phosphodiesterase (III/IV)-inhibitors and cytokines on mechanical properties of neutrophilic granulocytes in neonates and adults

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