ABSTRACT
Right ventricular (RV) and left ventricular (LV) dysfunction is common in a significant number of hospitalized coronavirus disease 2019 (COVID-19) patients. This study was conducted to assess whether the improved mitochondrial bioenergetics by cardiometabolic drug meldonium can attenuate the development of ventricular dysfunction in experimental RV and LV dysfunction models, which resemble ventricular dysfunction in COVID-19 patients. Effects of meldonium were assessed in rats with pulmonary hypertension-induced RV failure and in mice with inflammation-induced LV dysfunction. Rats with RV failure showed decreased RV fractional area change (RVFAC) and hypertrophy. Treatment with meldonium attenuated the development of RV hypertrophy and increased RVFAC by 50%. Mice with inflammation-induced LV dysfunction had decreased LV ejection fraction (LVEF) by 30%. Treatment with meldonium prevented the decrease in LVEF. A decrease in the mitochondrial fatty acid oxidation with a concomitant increase in pyruvate metabolism was noted in the cardiac fibers of the rats and mice with RV and LV failure, respectively. Meldonium treatment in both models restored mitochondrial bioenergetics. The results show that meldonium treatment prevents the development of RV and LV systolic dysfunction by enhancing mitochondrial function in experimental models of ventricular dysfunction that resembles cardiovascular complications in COVID-19 patients.
Subject(s)
Cardiotonic Agents/pharmacology , Methylhydrazines/pharmacology , Animals , COVID-19/complications , Cardiotonic Agents/therapeutic use , Cardiotoxicity/drug therapy , Disease Models, Animal , Endothelium/drug effects , Heart Failure/drug therapy , Heart Failure/metabolism , Heart Ventricles/drug effects , Hydrogen Peroxide/metabolism , Lung/drug effects , Male , Methylhydrazines/therapeutic use , Mice, Inbred C57BL , Mitochondria/drug effects , Oxygen Saturation/drug effects , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Reperfusion Injury/drug therapy , Stroke Volume/drug effects , Ventricular Dysfunction, Left/drug therapy , Ventricular Dysfunction, Right/drug therapy , COVID-19 Drug TreatmentABSTRACT
BACKGROUND: Acute respiratory compromise caused by complications of COVID-19, such as acute respiratory distress syndrome (ARDS) or thromboembolic disease, is a complex syndrome with unique challenges in treatment. Management often requires time and intensive care through a multiprofessional, multispecialty approach. Initial management is particularly challenging within the limited-resource environment of the emergency department (ED). The emergency physician's toolbox of treatments with reasonably rapid onset remains limited to respiratory support, prone positioning, steroids, and anticoagulation. CASE REPORT: We present a case of a patient with COVID-19 complicated by ARDS and bilateral pulmonary emboli with severe right ventricular dysfunction and systemic hypotension treated with nebulized nitroglycerin and systemic thrombolytic therapy in the ED. Serial evaluation of right ventricular function using point of care ultrasound over the next 2 h showed improvement of function with both agents as well as improvement in the patient's respiratory rate and work of breathing. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case describes a novel use of a widely available medication for patients with COVID-19-induced right ventricular dysfunction. Nebulized nitroglycerin may be an option to improve right ventricular function when other inhaled pulmonary vasodilators are not available in the initial ED setting. © 2021 Elsevier Inc.