Surrogate markers of tissue perfusion in models of tissue hypoxia

• Grant number: 05/03459-8
• Support Opportunities: Regular Research Grants
• Start date: December 01, 2005
• End date: November 30, 2009
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Eliezer Silva
• Grantee: Eliezer Silva
• 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

Abstract

Multiple Organ Dysfunction Syndrome is the main cause of death in intensive care units. This syndrome results form a complex pathophysiological process encompassing both tissue hypoxia and systemic inflammatory response. Tissue hypoxia in critically ill patients is secondary to three major mechanisms: low cardiac output, low arterial oxygen content (either by low hemoglobin level or by hypoxemia), and mitochondria dysfunction. Several surrogate markers have been used at bedside to reveal tissue hypoxia and to guide hemodynamic resuscitation, including lactate levels, mixed venous oxygen saturation and arterial-venous oxygen and CO2 gradients. However, all these markers have limitations, especially when they are individually analyzed. The present study will address the hypothesis that the combination of those surrogate markers could be used to reveal the exact time that tissue hypoxia takes place. Additionally, we will use tissue PO2, microcirculatory blood flow, and tissue ATP measurements to confirm tissue hypoxia. Thirty pigs will be monitored with aortic and pulmonary artery catheters. After splenectomy, portal vein will be cannulated and flow transducers will be placed around portal and renal veins. A tonometry catheter will be inserted into the jejunum. Lactate levels, O2 and CO2 gradients will be measured in arterial, mixed venous and portal venous blood samples. Finally, bare fiber sensors and microelectrodes will be placed in the muscles and jejunum mucosal. The animal will be divided in 4 groups: Sham (n=3): only surgical procedures; Stagnant hypoxia, n=9: progressive cardiac tamponade; Anemic hypoxia, n=9: progressive hemodilution (hemoglobin around 3 g/dL); Hypoxic hypoxia, n=9: animals under mechanical ventilation with FiO2 below 0.21. Every animal, except for sham group, will receive Lactate Ringer 5 ml/kg/h, over the whole experiment. The total time for each experiment will be 120 minutes. The animal will be sacrificed after the conclusion of the experiment. (AU)