Role of neurosympathetic pathways in the vascular response to sepsis

Purpose: The aim of this study was to determine the role of sympathetic neu ral activity in the hemodynamic adaptations to sepsis in pigs with an empha sis on circuit adaptations. A fall in resistance to venous return (RVR) was predicted in contrast to what was previously observed in sympathetically i ntact animals that had no change in RVR. Materials and Methods: We anesthetized and ventilated 13 pigs and gave 5 mg /kg of indomethacin. We measured cardiac output (CO) by thermodilution and measured pulmonary arterial (PAP), pulmonary capillary wedge (Pcw), right a trial pressure (Pra), and arterial pressure (MAP). Intermittent inflation o f a 50-mL balloon in the right atrium was used to transiently arrest the ci rculation for the measurement of mean circulatory filling pressure (MCFP). RVR was calculated from (MCFP - Pra)/CO. Animals were divided into two grou ps; 6 received 10 mg/kg of the ganglionic blocker, hexamethonium and norepi nephrine to maintain MAP; 7 had their spinal cords cut at C-2, After baseli ne measurements, all animals received 10 mu g/kg/h of endotoxin for 2 hours , and hemodynamic measurements were repeated. Plasma samples were obtained for measurements of immunoreactive endothelin-1 (ET-1), which was assayed b y a radioimmunoassay. Results: Hexamethonium had no significant effect on hemodynamics except for an increase in heart rate. After endotoxin, MAP and SVR fell, PAP rose, an d CO and RVR did not change. Spinal section resulted in an increase in hear t rate and small increase in PAP and MCFP. After endotoxin, there was a fur ther increase in heart rate, PAP, and MCFP with a marked fall in MAP and CO . RVR increased from 2.1 +/- 0.46 after spinal section to 3.6 +/- 54 mm min /L. (P < .05). ET-1 in the hexamethonium group (n = 2) rose from 2.21 +/- . 14 to 11.5 +/- 2.1 pg/ml at 2 hours, and in the spinal group (n = 7) from 2 .04 +/- 0.77 to 6.85 +/- 3.9 pg/mL at 45 minutes. Conclusion: Spinal section resulted in a more profound fall in blood pressu re and less increase in MCFP than in previously studied animals with sympat hetic nervous system intact, but there was still an increase in RVR and PAP ET-1 is a possible mediator of the increase in RVR and PAP Copyright (C) 1 998 by W.B. Saunders Company.