Inflammatory response induced by cardiopulmonary bypass in fetal lambs submitted to ischemic preconditioning

• Grant number: 14/15123-3
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: February 28, 2018
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Renato Samy Assad
• Grantee: Renato Samy Assad
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated researchers: Luiz Felipe Pinho Moreira ; Paulina Sannomiya ; Vera Demarchi Aiello

Abstract

Systemic inflammatory response (SIR) remains one of the major causes of cardiopulmonary bypass (CPB) associated organ injury in the majority of patients undergoing cardiovascular surgery, especially in neonates submitted to surgical correction of congenital heart lesions with CPB support. The mechanism of SIR during CPB includes the interaction of blood and artificial surface of the circuit and endotoxemia. As a result of series of chain reactions, numerous inflammatory mediators are formed and released, causing fever, leukocytosis, renal dysfunction and capillary leaking. In clinical setting, the most common SIR-related organ damage is pulmonary dysfunction, which often is manifested by increased interstitial edema and pulmonary vascular congestion. Remote ischemic preconditioning (rIPC) has been studied as a strategy to attenuate ischemia-reperfusion (IR) injury related to the effects of inflammatory mediators. The preconditioning stimulus has systemic effects to protect distant tissues from subsequent ischemia. At the present, there are no studies regarding preconditioning stimulus and fetal CPB, an important cause of mortality during and after the procedure. To test the hypothesis that remote ischemic preconditioning reduces fetal inflammatory response after CPB, 30 fetal lambs will be randomly assigned to 3 groups (Negative Control, Sham and Preconditioned Group). rIPC will be induced by four 5-minutes cycles of lower limb ischemia, paired with 2-minutes of reperfusion, before establishment of CPB. Systemic inflammatory mediators and vital organs will be assessed, aiming at attenuation of fetal systemic inflammatory response by rIPC during and after fetal CPB. (AU)