CENTRO DE INVESTIGACIONES CARDIOVASCULARES "DR. HORACIO EUGENIO CINGOLANI"
Unidad Ejecutora - UE
capítulos de libros
Lipid peroxidation and reperfusion injury in hypertrophied hearts
FANTINELLI JC; IA PÉREZ NUÑEZ; LF GONZÁLEZ ARBELÁEZ; MOSCA SM
In Tech Publisher
Año: 2012; p. 141 - 156
Oxidative stress is in part responsible of myocardial and endothelial dysfunction produced by ischemia and reperfusion. Thus, these alterations may be attenuated by interventions such as ¨ischemic preconditioning¨ (IP) and treatment with antioxidants. Accumulating evidence suggests that hypertension increases production of reactive oxygen species (ROS). However, the relationship between lipid peroxidation- consequent to ROS attack- and postischemic damage has not been clearly analyzed in hypertrophied hearts. Objective Our aim was to determine whether changes in lipid peroxidation and endogenous antioxidants are linked to cell death in non-preconditioned, preconditioned and treated with the scavenger N-(2-mercaptopropionyl)-glycine (MPG) hypertrophied hearts. Methods Isolated hearts from spontaneously hypertensive rats (SHR) were subjected to 35-min or 50-min global ischemia (GI) followed by 2-hour reperfusion (R). IP was induced by a single cycle of 5-min GI and 10-min R (IP1) or three cycles of 2-min GI and 5-min R (IP3) applied before to prolonged ischemia; MPG (2mM) was administered during 10 min before 50-min GI and the first 10 min of R. Infarct size (IS), systolic and diastolic myocardial function, coronary resistance (CR) were measured. Thiobarbituric acid reactive substances (TBARS) concentration- as an indicator of lipid peroxidation and reduced glutathione (GSH) content and cytosolic activity of SOD-as antioxidants were also determined. Results IP and MPG treatment significantly decreased the IS, improved the postischemic recovery of myocardial function and decrease CR. IP and MPG also decreased TBARS, preserved GSH content and decreased SOD cytosolic activity. There was a positive correlation between TBARS vs IS and TBARS vs CR and a negative correlation between GSH vs IS and GSH vs CR in all experimental situations. Conclusion: Our data show that: 1) the level of lipid peroxidation and antioxidant defenses determines the infarct size and 2) a decrease in lipid peroxidation consequent to an improvement of antioxidant systems appears as a mechanism responsible for the vascular and myocardial protection achieved by IP and MPG treatment in hypertrophied hearts.