Low-Dose Endotoxin Reduces Human Cerebrovascular Reactivity and Produces Procoagulant State
Stroke risk is increased in the presence of some infections. We studied potential mechanisms linking infections and stroke risk. We used endotoxin, a component of gram negative bacteria, as a standardized inflammatory stimulus. We infused low-dose endotoxin (1ng/kg) as a bolus in four healthy men, and analyzed cerebrovascular and hemostatic effects over 24 hours. We measured cerebral vasomotor reactivity, using transcranial Doppler ultrasonography to calculate breath-holding index (BHI); the latter consists of the percent change of middle cerebral artery blood flow velocity over time during breath holding. We also measured thrombin-antithrombin complexes (TAT, an index of thrombin generation), and soluble e-selectin (a marker of endothelial activation). Following infusion of endotoxin, there were substantial physiological changes primarily at three to six hours post-infusion. Temperature peaked at 100 °F (p<.05), with no significant change in mean arterial pressure. BHI showed maximum decline from 1.55 ± 0.88 to 0.33 ± 0.35 %/sec (p<.05). TAT levels increased from 3.0 ± 0.9 to 41.0 ± 21.1 ug/ml (p<.05). Soluble e-selectin levels increased from 66.6 ± 35.2 to 207.4 ± 78.9 ug/ml (p<.05). These findings indicate that a standardized low-dose inflammatory stimulus produces a marked decline in human cerebrovascular reactivity while simultaneously inducing a procoagulant state with endothelial activation . The reduction in cerebrovascular reactivity combined with a procoagulant state may contribute to increased stroke risk in this setting.