Physiological Effects of Lactate in Individuals With Chronic Heart Failure

Background: Lactate is continuously produced in the human body through two primary processes: glycolysis and microbial fermentation in the gastrointestinal tract. At rest, its concentration in the bloodstream typically ranges from 1 to 2 mmol/L. However, during periods of physical exertion or insufficient oxygen supply, such as during intense exercise, lactate levels significantly increase. Traditionally, lactate was perceived as a byproduct of anaerobic metabolism. Nevertheless, emerging research has illuminated its vital role as both a signaling molecule and a crucial energy source for vital organs like skeletal muscle, brain, and the heart. Objectives: The primary aim of this study is to investigate the impact of physiological levels of circulating lactate on the hemodynamics of individuals with chronic heart failure. This research seeks to understand how lactate affects the cardiovascular response in this specific patient population. Design and Endpoints: The study design employs a double-blind, randomized crossover approach involving 12 heart failure patients. Each participant will undergo two separate visits. Visit 1: Participants will receive a three-hour intravenous infusion of either a racemic (D/L) mixture of sodium lactate or an intravenous isotonic sodium chloride placebo, with a subsequent crossover to the opposite infusion on the same day. Visit 2: Similar to the first visit, participants will receive either an orally administered racemic (D/L) mixture of sodium lactate or an isocaloric, isovolumic oral placebo (maltodextrin), with a crossover to the opposite administration after three hours. The study's endpoints include cardiac output (primary), mixed venous saturation (SVO2), pulmonary wedge pressure, resting echocardiography (left ventricular ejection fraction and myocardial work efficiency), and measurements of vasoactive substances in blood samples. Methods: The study employs invasive Swan-Ganz monitoring to measure cardiac output, echo