Endothelial-dependent relaxation response alerations during acute and chronic sepsis.

摘要

Septic shock has been demonstrated to cause reduced reactivity of microvessels with intact endothelium. The objective of this study was to determine changes in the endothelial-dependent relaxation response progressing from acute to chronic sepsis in skeletal muscle. Using a novel sponge inoculation model for inducing sepsis, at 4, 24, and 72 hours following the initiation of sepsis, the endothelial-dependent relaxation response of the cremaster microcirculation in pentobarbital-anesthetized rats was determined via in vivo videomicroscopy. Hemodynamics were also assessed continuously throughout the experiment. The first order arterioles and venules were unresponsive to increasing concentrations of acetylcholine (10{dollar}sp{lcub}-9{rcub}{dollar} to 10{dollar}sp{lcub}-5{rcub}{dollar} M) in both saline control and infected animals at all time points. This finding indicates that these microvessels were dilated from the beginning of the experiment. Fourth order arterioles demonstrate an increase in sensitivity to acetylcholine (12.5%, p {dollar}<{dollar} 0.05) 4 hours following bacterial inoculation suggesting an increase in constitutive nitric oxide synthase at this time point. Third and fourth order arterioles demonstrate a depressed endothelial-dependent relaxation response 72 hours following bacterial inoculation (14.1% and 14.9% respectively, p {dollar}<{dollar} 0.05). This response is indicative of a decreased sensitivity to acetylcholine due to either a disruption of the signal transduction pathway or an imbalance of vasoactive agents.