Physiological Effects of Lactate in Individuals With Chronic Heart Failure

Summary

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, echocardiography, and frequent venous blood sample collections. These measurements and samples will be taken at specific intervals during the study visits.

Intervention:

To investigate the isolated hemodynamic and physiological effects of lactate, the study utilizes lactate infusion and ingestion to induce a state of hyperlactatemia within the physiological range. The intended dosages aim to stay within the physiological range, with no values expected to exceed 3-4 mmol/L.

Conditions

• Heart Failure, Systolic

Interventions

OTHER

Sodium lactate infusion

Dosage of sodium-lactate: 0.5 mol/L; 3 mL/kg/time; maximal 300 mL/hour.

OTHER

Sodium lactate ingestion

Oral dose is equal to the i.v. dose.

Sponsors & Collaborators

• Henrik Wiggers

  lead OTHER

Principal Investigators

• Henrik Wiggers, Professor · Dept. of Cardiology, Aarhus University Hospital

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-11-22

Primary Completion

2025-01-16

Completion

2025-01-16

Countries

• Denmark

Study Locations