Role of neurosympathetic pathways in the vascular response to sepsis.
OBJECTIVE
The aim of this study was to determine the role of sympathetic neural activity in the hemodynamic adaptations to sepsis in pigs with an emphasis on circuit adaptations. A fall in resistance to venous return (RVR) was predicted in contrast to what was previously observed in sympathetically intact animals that had no change in RVR.


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 atrial pressure (Pra), and arterial pressure (MAP). Intermittent inflation of a 50-mL balloon in the right atrium was used to transiently arrest the circulation for the measurement of mean circulatory filling pressure (MCFP). RVR was calculated from (MCFP - Pra)/CO. Animals were divided into two groups; 6 received 10 mg/kg of the ganglionic blocker, hexamethonium and norepinephrine to maintain MAP; 7 had their spinal cords cut at C-2. After baseline measurements, all animals received 10 microg/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 by 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, and CO and RVR did not change. Spinal section resulted in an increase in heart rate and small increase in PAP and MCFR After endotoxin, there was a further 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 x 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.


CONCLUSIONS
Spinal section resulted in a more profound fall in blood pressure and less increase in MCFP than in previously studied animals with sympathetic 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.
Magder
S
S
Division of Critical Care, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.
Rastepagarnah
M
M
D000222:Adaptation, Physiological; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003714:Denervation; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D005730:Ganglionic Blockers / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D018805:Sepsis / Q000097:blood / Q000503:physiopathology*; D013116:Spinal Cord / Q000601:surgery; D013552:Swine; D013564:Sympathetic Nervous System / Q000187:drug effects
D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D005730:Ganglionic Blockers; D018738:Hexamethonium; D007213:Indomethacin