Proceedings of The Physiological Society

University of Oxford (2011) Proc Physiol Soc 23, PC215

Poster Communications

Cerebral oxygen vasoreactivity after lipopolysaccharide infusion in healthy humans

R. M. Berg1, K. A. Evans2, R. R. Plovsing3, C. B. Christiansen1, N. Holstein-Rathlou4, D. M. Bailey2, K. Møller1,5

1. Centre of Inflammation and Metabolism, M7641, University Hospital Rigshospitalet, Copenhagen

  • Figure 1. Effects of a four-hour lipopolysaccharide (LPS) infusion on cerebral oxygen vasereactivity (COVR) in ten healthy humans (mean

Sepsis, the systemic inflammatory response to infection, is frequently complicated by brain dysfunction, which may involve disturbances in cerebral oxygen transport. We have previously established lipopolysaccharide (LPS) infusion as a human-experimental model of systemic inflammation that mimics the early stages of sepsis (Taudorf et al. 2007). In the present study, we hypothesised that LPS infusion impairs cerebral oxygen vasoreactivity (COVR). Ten healthy male volunteers aged 23 (mean, SD 2) years were enrolled in the study. A catheter was inserted in the radial artery, and volunteers underwent a four-hour intravenous infusion of Escherichia coli LPS (total dose of 2 ng/kg). Prior to the infusion and immediately after, cortical oxygenation and middle cerebral artery blood flow velocity (MCAv) were measured by dual-wavelength near-infrared light spectroscopy and transcranial Doppler ultrasonography, respectively. During measurements, three interventions were conducted in a randomised fashion using a closed system (Ambu 'E' valve) with a tight-fitting mask: 20 minutes of normoxia (21% O2), 20 minutes of hyperoxia (40% O2), and 20 minutes of hypoxia (12% O2). To avoid the contaminating effects of hypocapnia-mediated vasoconstriction, all interventions were conducted in eucapnia by continuously monitoring and adjusting end-tidal CO2. The cerebrovascular resistance (CVR) was calculated as mean arterial pressure/MCAv, and the arterial blood content of oxygen (CaO2) was calculated as Hgb x SaO2 + PaO2 x 0.01, where Hgb is the haemoglobin concentration, and SaO2 and PaO2 is the arterial oxygen saturation and partial pressure of oxygen, respectively. COVR was subsequently calculated as the change in CVR per mmol change in CaO2 by linear regression. The pro-inflammatory cytokine tumour necrosis factor alpha (TNF) was measured in arterial plasma by use of a Multiplex assay (Luminex). LPS induced an immense systemic inflammatory response with fever, flu-like symptoms, neutrocytosis, and a 34 (mean, SD 12)-fold increase in the circulating levels of TNF (all P < 0.001). However, LPS infusion per se neither influenced CaO2, cortical oxygenation (both NS), or COVR (Figure 1). Although LPS-infusion induced a marked systemic inflammatory response, it did not appear to affect COVR. Our data suggest that COVR is intact, at least in the early stages of sepsis. Future studies should address other potential mechanisms of sepsis-associated brain dysfunction, such as impaired cerebral blood flow autoregulation and CO2 reactivity.

Where applicable, experiments conform with Society ethical requirements