Lactate Metabolism After an Endotoxin Challenge in Healthy Humans

Effects of an Acute Administration of Bacterial Endotoxin on Whole Body and Regional Lactate Metabolism in Healthy Male Volunteers

Sepsis is characterized by hyperlactatemia, the severity of which is proportionate with sepsis severity. The pathophysiological mechanisms (increased lactate production vs decreased lactate utilization; tissues involved in sepsis-induced lactate production) remain largely unknown.

In this study, the investigators will assess whole body and regional metabolism in healthy young male subjects on two occasions, once after administration of an intravenous bacterial endotoxin challenge, and once without intervention.

In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge

• Energy expenditure and net substrate oxidation rates (indirect calorimetry)
• Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion)
• Glucose kinetics (measured with 6,6 d2 glucose)
• Hemodynamic parameters and body temperature
• Blood clinical chemistry In one group of subjects, whole body lactate metabolism will be measured over 10 hours after the endotoxin challenge
• Energy expenditure and net substrate oxidation rates (indirect calorimetry)
• Lactate kinetics (measured by means of a continuous, exogenous sodium lactate infusion)
• Glucose kinetics (measured with 6,6 d2 glucose)
• Hemodynamic parameters and body temperature
• Blood clinical chemistry

In a second group of subjects, regional muscle lactate metabolism will be measured over 10 hours after the endotoxin challenge by means of muscle microdialysis

Inclusion Criteria:

• gender male
• body mass index (BMI) < 25 kg/m2
• absence of known disease

Exclusion Criteria:

• any known pathology
• abnormal cardio-pulmonary and hemodynamic status
• electrocardiographic alterations
• history of allergy
• current medications
• drug abuse
• consumption of more than 20g/day alcohol