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Mechanisms of hypertonic saline solution associated to pentoxifylline and ethy-pyruvate in the reduction of multiple organ dysfunctions after trauma, sepsis and ischemia-reperfusion

Abstract

Our goal is to investigate the mechanisms by which hypertonic saline solution, associated to pentoxifylline and ethyl-piruvate may attenuate multiple organ dysfunctions after trauma, sepsis and ischemia-reperfusion, a major health worldwide problem due to its prevalence and to the high associated morbidity and mortality. We will test the hypothesis that hypertonic saline solution, associated to pentoxifylline, and/or ethyl-piruvate used in the treatment of hemorrhagic or septic shock, and of ischemia-reperfusion of large territories induced by surgical maneuvers, decreases multiple organ dysfunction due to its beneficial effects, particularly in the hepatosplanchnic area, through hemodynamic improvement at the macro and microcirculatory levels, by reducing ischemia-reperfusion injury and systemic inflammatory response, and preserving cellular function. Using clinically relevant experimental models of uncontrolled hemorrhage, sepsis by live bacteria injection, and ischemia-reperfusion by surgical maneuvers, we will evaluate the systemic and regional hemodynamic effects and the mechanisms by which such solutions may reduce multiple organ dysfunction in pigs. Complex organ function monitoring for a longer period (72 hours) than in our previous studies, and the maintenance of these animals in a facility similar to intensive care units is a critical step before testing the potential clinical use of those solutions. In parallel, we will be conducting studies in small animal models of hemorrhage, sepsis and ischemia-reperfusion addressing important aspects of the microcirculatory, cellular and inflammatory effects of those solutions, which remain to be understood. (AU)

Scientific publications (6)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ZANONI, FERNANDO LUIZ; MIRANDA COSTA CRUZ, JOSE WALBER; MARTINS, JOILSON OLIVEIRA; BENABOU, SIMON; GRECO, KARIN VICENTE; RAMOS MORENO, ANA CAROLINA; MARTINEZ, MARINA BAQUERIZO; CALDERARO, FRANCO FERRARO; ROCHA E SILVA, MAURICIO; SANNOMIYA, PAULINA. HYPERTONIC SALINE SOLUTION REDUCES MESENTERIC MICROCIRCULATORY DYSFUNCTIONS AND BACTERIAL TRANSLOCATION IN A RAT MODEL OF STRANGULATED SMALL BOWEL OBSTRUCTION. Shock, v. 40, n. 1, p. 35-44, JUL 2013. Web of Science Citations: 8.
ERLING JUNIOR, NILON; DE SOUZA MONTERO, EDNA FRASSON; SANNOMIYA, PAULINA; POLI-DE-FIGUEIREDO, LUIZ FRANCISCO. Local and remote ischemic preconditioning protect against intestinal ischemic/reperfusion injury after supraceliac aortic clamping. Clinics, v. 68, n. 12, p. 1548-1554, 2013. Web of Science Citations: 14.
ERLING, JR., NILON; NAKAGAWA, NAOMI KONDO; MIRANDA COSTA CRUZ, JOSE WALBER; ZANONI, FERNANDO LUIZ; COSTA BAPTISTA-SILVA, JOSE CARLOS; SANNOMIYA, PAULINA; POLI-DE-FIGUEIREDO, LUIZ FRANCISCO. Microcirculatory effects of local and remote ischemic preconditioning in supraceliac aortic clamping. JOURNAL OF VASCULAR SURGERY, v. 52, n. 5, p. 1321-1329, NOV 2010. Web of Science Citations: 7.
BALBINO, MARCOS; CAPONE NETO, ANTONIO; PRIST, RICARDO; FERREIRA, ALICE TEIXEIRA; POLI-DE-FIGUEIREDO, LUIZ F. Fluid Resuscitation With Isotonic or Hypertonic Saline Solution Avoids Intraneural Calcium Influx After Traumatic Brain Injury Associated With Hemorrhagic Shock. JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE, v. 68, n. 4, p. 859-864, APR 2010. Web of Science Citations: 7.
ZANONI, FERNANDO LUIZ; BENABOU, SIMON; GRECO, KARIN VICENTE; RAMOS MORENO, ANA CAROLINA; MIRANDA COSTA CRUZ, JOSE WALBER; FILGUEIRA, FERNANDO PARANAIBA; MARTINEZ, MARINA BAQUERIZO; POLI DE FIGUEIREDO, LUIZ FRANCISCO; ROCHA E SILVA, MAURICIO; SANNOMIYA, PAULINA. MESENTERIC MICROCIRCULATORY DYSFUNCTIONS AND TRANSLOCATION OF INDIGENOUS BACTERIA IN A RAT MODEL OF STRANGULATED SMALL BOWEL OBSTRUCTION. Clinics, v. 64, n. 9, p. 911-919, 2009. Web of Science Citations: 23.
NAKAGAWA, NAOMI K.; JUKEMURA, JOSÉ; AIKAWA, PRISCILA; NOGUEIRA, RAFAEL A.; POLI-DE-FIGUEIREDO, LUIZ F.; SANNOMIYA, PAULINA. In vivo observation of mesenteric leukocyte-endothelial interactions after cecal ligation/puncture and surgical sepsis source control. Clinics, v. 62, n. 3, p. 321-326, 2007.

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