Mechanical ventricular unloading in advanced heart failure (HF) has been shown to induce reverse remodeling in myocardial tissues. Little is known about the impact of ventricular unloading on myocardial energy metabolism. We hypothesized that left ventricular unloading reduces myocardial mitochondrial reactive oxygen species (ROS) production and improves mitochondrial coupling efficiency in patients suffering from advanced HF. Left ventricular tissue specimens were harvested from explanted hearts at the time of transplantation. We compared myocardial metabolism in explanted hearts supported with an unloading ventricular assist device prior to transplantation (LVAD-HTX; n = 9) with tissue specimens of unsupported failing hearts (HTX; n = 6). Myocardial mitochondrial ROS production was decreased by 40% in LVAD-HTX compared to HTX patients (1.5 ± 0.3 vs. 0.9 ± 0.1 pmol/(s/mg); p < 0.05). High-resolution respirometry revealed increased mitochondrial coupling efficiency in LVAD-HTX patients (respiratory/control ratio 1.7 ± 0.2 vs. 1.2 ± 0.2; p < 0.05). In conclusion, ventricular unloading is related to decreased mitochondrial ROS production and increased coupling efficiency in myocardium of human failing hearts, suggesting a novel pathomechanism of unloading-associated cardioprotection.
Keywords: Heart failure; Heart transplantation; High-resolution respirometry; Left ventricular assist device; Left ventricular unloading; Mitochondrial respiration; Myocardial energy metabolism; Reactive oxygen species.