Complement activation, endothelin-1 and neuropeptide Y in relation to the cardiovascular response to endotoxin-induced systemic inflammation in healthy volunteers
Endotoxin is a major stimulus for triggering the host response in septicaemia. The pathophysiology of sepsis involves activation of the vascular endothelium and leukocytes, resulting in the release of various mediators, e.g. cytokines, nitric oxide (NO), endothelin (ET-1) and complement factors. We evaluated the blood levels of complement activation, ET-1 and neuropeptide Y (NPY) in parallel with the haemodynamic and oxygen transport response during human experimental endotoxemia. Methods:
Eleven healthy men had venous, arterial and pulmonary arterial catheters placed for continuous haemodynamic measuring. After 30 min rest endotoxin (E. Coli 4 ng kg−1, Lot G1) was intravenously administered. Blood samples from pulmonary and arterial catheters were collected hourly over 4 h. Results:
Body temperature augmented significantly from baseline values (36.7 ± 0.7 °C, mean ± SEM) with a maximum after 3.5 h (39.1 ± 0.3 °C, P < 0.001). Cardiac output increased by 100%, systemic vascular resistance decreased by 50%, the oxygen consumption and the tissue oxygen transport increased. Activation of the complement system was indicated by an increase in SC5b-9. Endothelin-1-like immunoreactivity (ET-1-LI) increased over time in arterial blood. NPY-like immunoreactivity (NPY-LI) did not change over time. Conclusion:
A dose of endotoxin associated with reproducible systemic vasodilation and fever in healthy subjects causes complement activation and increased systemic levels of ET-1-LI, illustrating that the model is a useful tool for inducing moderate systemic inflammation where several mediator systems are activated.
Document Type: Research Article
Affiliations: 1: Department of Anaesthesiology and Intensive Care, Center for Surgical Sciences, Huddinge University Hospital, 2: Department of Anaesthesiology and Intensive Care, Danderyds Hospital, 3: Department of Surgical Sciences, Section of Anaesthesiology and Intensive Care, Karolinska Hospital, 4: Department of Physiology and Pharmacology, Karolinska Institutet, all at Karolinska Institutet, Stockholm; 5: Department of Anaesthesiology and Intensive Care, Sahlgrenska University Hospital, Institute of Surgical Sciences, Göteborg, Sweden
Publication date: January 1, 2004