Comparison of the haemodynamic effects of nitric oxide synthase inhibition and nitric oxide scavenging in endotoxaemic sheep. 1998

H G Bone, and R Waurick, and H Van Aken, and M Booke, and T Prien, and J Meyer
Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Münster, Germany. bone@uni-muenster.de

OBJECTIVE The present study compared the effects of nitric oxide (NO) synthase inhibition and NO scavenging with haemoglobin in endotoxaemic sheep. METHODS 12 sheep were instrumented for chronic study. Six sheep received LG-nitro-arginine-methylester (L-NAME, 2.5 mg/kg bolus followed by a continuous infusion of 0.5 mg/kg per h), the other 6 sheep received pyridoxalated haemoglobin polyoxyethylene conjugate (PHP, 100 mg/kg bolus followed by a continuous infusion of 20 mg/kg per h). RESULTS Haemodynamic and oxygenation parameters were measured in healthy sheep, after infusion of Salmonella typhosa endotoxin (10 ng/kg per min) for 24 h and after infusion of L-NAME or PHP. The infusion of endotoxin resulted in a hypotensive, hyperdynamic circulation. Infusion of L-NAME increased mean arterial pressure (MAP) from 76.1 +/- 4.2 mmHg to normal values of 95.8 +/- 5.7 mmHg (p < 0.05). PHP increased MAP from 73.0 +/- 3.0 to 88.6 +/- 4.7 mmHg (p < 0.05). This increase in MAP was associated in the L-NAME group with a more prominent drop in cardiac index (from 10.2 +/- 0.4 to 7.0 +/- 0.51.min-1.m-2; p < 0.05) than in the PHP group (from 10.7 +/- 0.2 to 9.3 +/- 0.61.min-1.m-2). During the first 90 min of infusion, cardiac index remained lower in the L-NAME group than in the PHP group. The increase in pulmonary vascular resistance was also higher in the L-NAME group. CONCLUSIONS These results suggest, that at the doses used in the experiment, NO scavenging with PHP has smaller effects on cardiac index and pulmonary vascular resistance than NO synthase inhibition with L-NAME. Therefore, the concept of NO scavenging in hyperdynamic sepsis should be further evaluated.

UI MeSH Term Description Entries
D010101 Oxygen Consumption The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346) Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006439 Hemodynamics The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM. Hemodynamic
D006454 Hemoglobins The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Eryhem,Ferrous Hemoglobin,Hemoglobin,Hemoglobin, Ferrous
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012485 Salmonella typhi A serotype of SALMONELLA ENTERICA which is the etiologic agent of TYPHOID FEVER. Salmonella enterica serovar Typhi,Salmonella typhosa
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D014435 Typhoid Fever An acute systemic febrile infection caused by SALMONELLA TYPHI, a serotype of SALMONELLA ENTERICA. Enteric Fever,Typhus, Abdominal,Salmonella typhi Infection,Typhoid,Abdominal Typhus,Enteric Fevers,Fever, Enteric,Fever, Typhoid,Fevers, Enteric,Fevers, Typhoid,Infection, Salmonella typhi,Infections, Salmonella typhi,Salmonella typhi Infections,Typhoid Fevers,Typhoids
D019331 NG-Nitroarginine Methyl Ester A non-selective inhibitor of nitric oxide synthase. It has been used experimentally to induce hypertension. L-NAME,N omega-Nitro-L-arginine Methyl Ester,NG-Nitro-L-Arginine Methyl Ester,N(G)-Nitro-L-arginine Methyl Ester,N(G)-Nitroarginine Methyl Ester,N(omega)-Nitro-L-arginine Methyl Ester,NG-Nitroarginine Methyl Ester, D-Orn-Isomer,NG-Nitroarginine Methyl Ester, L-Orn-Isomer, Monohydrochloride,Methyl Ester, NG-Nitro-L-Arginine,Methyl Ester, NG-Nitroarginine,N omega Nitro L arginine Methyl Ester,NG Nitro L Arginine Methyl Ester,NG Nitroarginine Methyl Ester,NG Nitroarginine Methyl Ester, D Orn Isomer

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