Increased organ blood flow in chronic endotoxemia is reversed by nitric oxide synthase inhibition.
We evaluated regional blood flows in a hyperdynamic sepsis model and the reversal of increased flows by blockade of nitric oxide (NO) synthase. Seven awake sheep were continuously infused with Escherichia coli endotoxin [lipopolysaccharide (LPS), 10 ng.kg-1.min-1] for 48 h. The NO synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg) was injected after 24 h. Blood flows to systemic organs were determined with the radioactive microsphere technique. LPS induced elevation of cardiac index by 36% (P < 0.05) and a fall in systemic vascular resistance index by 37% (P < 0.05) at 0 h [time of L-NAME administration, 24 h after infusion of LPS had begun] L-NAME administration normalized cardiac index [6.1 +/- 0.5 at 4 h posttreatment, 6.1 +/- 0.5 l.min-1.m-2 at -24 h (baseline)] and systemic vascular resistance index (1,333 +/- 105 at 4 h posttreatment, 1,280 +/- 163 dyn.s.cm-5.m2 at -24 h) and reduced all regional blood flows to near-baseline levels for the remainder of the study period (24 h). O2 consumption was unaffected by treatment.
Meyer
J
J
Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-1091.
Hinder
F
F
Stothert
J
J
Traber
L D
LD
Herndon
D N
DN
Flynn
J T
JT
Traber
D L
DL
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002908:Chronic Disease; D004926:Escherichia coli; D005260:Female; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008070:Lipopolysaccharides; D008863:Microspheres; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D014115:Toxemia / Q000503:physiopathology*; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D007773:Lactates; D008070:Lipopolysaccharides; D019344:Lactic Acid; D013929:Thromboxane B2; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester