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Study of the cardioprotective effects of esmolol in an experimental model of septic shock

Grant number: 11/21327-2
Support Opportunities:Regular Research Grants
Duration: June 01, 2012 - May 31, 2014
Field of knowledge:Health Sciences - Medicine - Surgery
Principal Investigator:José Otávio Costa Auler Junior
Grantee:José Otávio Costa Auler Junior
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated researchers:Denise Aya Otsuki


Septic shock is responsible for approximately 10% of the admissions to intensive care units (1), with an unnaceptable rate of mortality still nowadays. New treatments, such as the use of beta-blockers, have demonstrated benefits on the metabolism, cytokine expression and myocardial function in septic patients (2). Objective: Evaluate the effects of the esmolol infusion in the myocardium in an experimental swine model of septic shock.Experimental design: Twenty female pigs submitted to experimentally induced sepsis through E. coli infusion will be used. The animals will be randomized in three groups: NE group, where the animals will receive treatment with fluid resuscitation and norepinephrine to keep MAP > 65mmHg and CVP between 8-12mmHg; and NEBETA group, where the same treatment will be established with the addiction of a esmolol infusion titrated to reduce in 20% the heart rate. The animals will be evaluated in a baseline moment, considered as 30 minutes after finishing the instrumentation; immediately after and 30 minutes after sepsis induction, and then at each every hour, during 12 hours. The heart rate variability (HRV) will also be evaluated where fluid resuscitation or norepinephrine are required. Hemodynamic and respiratory parameters, oxygenation and perfusion, urine output, lactate, glucose; cytokine, cardiac troponin I and B-type natriuretic peptide levels and HRV will be evaluated. In the end of the experimental procedure, myocardial samples will be collected for histological analysis. For data comparison between times within the same group, the analysis of variance with repeated measures (RM-ANOVA) is going to be used, followed by Tukey test when necessary. The comparison among groups will be performed using the Student t test (p < 0.05). (AU)

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