title: Levosimendan increases portal blood flow and attenuates intestinal intramucosal acidosis in experimental septic shock.
abstract: It has been proposed that vasodilatory therapy may increase microcirculatory blood flow and improve tissue oxygenation in septic shock. The authors aimed to evaluate the effects of levosimendan in systemic and splanchnic hemodynamics in a porcine model of septic shock in a randomized animal controlled study. This study was performed in an animal research facility in a university hospital. Anesthetized pigs were monitored with a pulmonary artery catheter and an ultrasonic blood flow probe in the portal vein for measurement of systemic and portal blood flows and with a tonometer placed in the small intestine for measurement of the intramucosal-arterial PCO2 gap. Three groups of pigs were studied: nonseptic (n = 7), septic (n = 7), and septic treated with levosimendan (n = 7). Levosimendan was administered i.v. at t = -10 min (200 microg/kg in i.v. bolus followed by 200 microg/kg per h). Sepsis was induced at t = 0 min by the administration of live Escherichia coli. Vascular reactivity was tested by the hemodynamic response to noradrenaline. Levosimendan markedly attenuated the sepsis-induced increase in pulmonary vascular resistance, decrease in portal/systemic blood flow, oliguria, impairment in oxygenation, hyperkalemia, and the widened intramucosal-arterial PCO2 gap. Systemic blood pressure and vascular resistance did not differ as compared with the septic untreated group. Responses to noradrenaline significantly improved in animals treated with levosimendan. Treatment with levosimendan in this animal model of sepsis attenuated pulmonary vasoconstriction and improved portal blood flow, intestinal mucosal oxygenation, pulmonary function, and vascular reactivity.
authors.affiliation: Hospital Universitario de Getafe, European University of Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: García-Septien
authors.forename: José A
authors.initials: JA
authors.lastname: Lorente
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Delgado
authors.forename: Marta
authors.initials: M
authors.lastname: de Paula
authors.forename: Nicolás
authors.initials: N
authors.lastname: Nin
authors.forename: Amelia
authors.initials: A
authors.lastname: Moscoso
authors.forename: Alberto
authors.initials: A
authors.lastname: Sánchez-Ferrer
authors.forename: Francisco
authors.initials: F
authors.lastname: Perez-Vizcaino
authors.forename: Andrés
authors.initials: A
authors.lastname: Esteban
mesh_terms: D000138:Acidosis / Q000188:drug therapy*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015687:Cell Hypoxia / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004927:Escherichia coli Infections / Q000150:complications / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006835:Hydrazones / Q000494:pharmacology* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000187:drug effects*; D008102:Liver Circulation / Q000187:drug effects*; D008833:Microcirculation / Q000187:drug effects; D023421:Models, Animal; D010538:Peritonitis / Q000150:complications / Q000503:physiopathology; D011168:Portal System / Q000187:drug effects*; D011724:Pyridazines / Q000494:pharmacology* / Q000627:therapeutic use; D012772:Shock, Septic / Q000209:etiology / Q000503:physiopathology*; D000077464:Simendan; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan