Regional heterogeneity of decreased myocardial norepinephrine and increased lipid peroxidation levels in patients with end-stage failing heart secondary to dilated or ischemic cardiomyopathy.

BACKGROUND: Regional alterations in norepinephrine (NE) and lipid peroxidation in the myocardium of patients with heart failure is not well known. This study was designed to investigate regional myocardial NE levels and lipid peroxidation index and their relationships with the functional parameters in two pathologic conditions: dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM). METHODS: Biopsied heart samples were obtained from 13 DCM and 10 ICM patients (orthotopic cardiac transplantation). Tissue NE was assayed by high-pressure liquid chromatography with electrochemical detection. Tissue lipid peroxidation (malondialdehyde, MDA) was evaluated by the thiobarbituric acid (TBA) reaction. RESULTS: Non-failing hearts (controls, n = 4) were included in this study for comparison. Left ventricular dysfunction was present at rest with a mean left ventricular ejection fraction (LVEF) of 19.1 +/- 2.6% for DCM patients and 17.4 +/- 2.0% for ICM patients. The amount of NE in control hearts was significantly lower (p < 0.05) than in DCM or ICM hearts. For all patients, there were several differences in distribution of NE among the sub-divisions of the atria and ventricles studied. NE content was significantly higher in the right atria than in the left atria or ventricles. A significant correlation between LVEF and NE concentrations was observed in the left septum of ICM and DCM patients and in the left ventricle of the ICM group. In DCM and ICM patients, some parts of the left ventricle showed higher levels of lipid peroxides compared with controls. MDA levels in patients with DCM varied little from one region to another, whereas in ICM patients there was considerable variation. CONCLUSIONS: This study is the first demonstration of a correlation between the values of pre-operative LVEF and cardiac NE concentrations in specific parts of the myocardium. This effect could not be generalized to the entire heart. The pattern of myocardial MDA distribution did not follow that of the NE distribution.

Increase in Levels of BDNF is Associated with Inflammation and Oxidative Stress during Cardiopulmonary Bypass.

Cardiopulmonary Bypass (CPB) is thought to generate reactive oxygen species associated with a systemic inflammation and neurotrophins seem to be involved in cardiovascular inflammatory reactions. The aim of this study was to determine the impact of CPB on plasma neurotrophins levels and to appreciate the links existing between inflammation, oxidative stress and neurotrophins. Blood samples were taken from 27 patients undergoing cardiac surgery: before CPB, during ischemia and at reperfusion under CPB. Oxidative stress was evaluated using an Electron Spin Resonance technique by superoxide detection, and antioxidant defences by measurement of Endogenous Peroxidase Activity (EPA). The evolution of two neurotrophins: Brain Derived Neurotrophic Factor (BDNF) and Nerve Growth Factor (NGF) was assessed with an ELISA method. An inflammatory index was determined by a multiplex flow cytometry method. The inflammatory index showed that MCP-1, P-selectin, t-PA and interleukins 6, 8 and 10 levels increased during CPB (p<0.05). Superoxide production and EPA were higher during ischemia and reperfusion than before CPB (p<0.05). BDNF plasma levels were higher at reperfusion (p<0.05). NGF levels did not change. Our study shows an increase of BDNF levels, associated with an inflammatory phenomenon and a redox modification, in the plasma of patients undergoing cardiac surgery under CPB. The role played by this neurotrophin in this complex situation still needs to be elucidated, in particular its cellular origin. It is also necessary to understand whether BDNF has a beneficial or deleterious effect during CPB.