Abstract 3744: Measurement of Myocardial Free Radical Production in Patients with Congestive Heart Failure Using EPR Spectroscopy
Increased myocardial free radical (ROS) production may contribute to the pathogenesis of congestive heart failure (CHF). In humans, indirect measurements of oxidative stress are increased in blood and pericardial fluid and tissue samples harvested at the time of transplantation demonstrate an increase in ROS production when measured by electron paramagnetic spectroscopy (EPR). However, no previous direct measurements of ROS production have been made in the intact human heart. Six patients (63±3 years) with severe LV dysfunction (LVEF − 33±3 %) were studied during implantation of a biventricular pacemaker. ROS production was measured in Aortic and Coronary Sinus (CS) blood during rest and in response to rapid pacing (140 bpm x 2mins) using EPR spectroscopy in conjunction with the spin trap PBN (0.14 mol/L). Samples were extracted in toluene and were deoxygenated for 15 minutes at 25 degrees C over nitrogen to increase the sensitivity of the EPR signal. ( 70 G scan width, 100 kHz field modulation, microwave frequency = 9.378 GHz, power = 20 mW, magnetic field center = 3,345 G, receiver gain = 90dB and number of scans = 30 to 90 ). Increased myocardial work with pacing decreased systolic pressure from 112±8 to 98±3 and was accompanied by a decrease in the CS PO2 from 26 to 22 mmHg. Aortic and CS levels of ROS were not different at rest but significantly increased during rapid pacing. The hyperfine splitting constants were consistent with a carbon and/or oxygen centered alkoxyl radical. These results demonstrate for the first time a measurable EPR signal in the intact human heart.