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Response of the septic vasculature to prolonged vasopressor therapy with N(omega)-monomethyl-L-arginine and epinephrine in canines.
- Source :
-
Critical care medicine [Crit Care Med] 1998 May; Vol. 26 (5), pp. 877-86. - Publication Year :
- 1998
-
Abstract
- Objective: To investigate the effect of blocking nitric oxide production on cardiovascular function and survival in canine septic shock treated with or without a conventional vasopressor.<br />Design: Randomized, controlled trial.<br />Setting: An animal research laboratory at the National Institutes of Health.<br />Subjects: Sixty purpose-bred beagles.<br />Interventions: Fibrin clots containing Escherichia coli were surgically placed into the peritoneal cavity. N(omega)-monomethyl-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr), epinephrine (1 microg/kg/min), both, or neither were infused for 24 hrs beginning 6 hrs after the onset of infection. All animals received fluid and antibiotic therapy.<br />Measurements and Main Results: Serum nitric oxide metabolites, nitrite and nitrate, increased with infection (p = .024) and decreased with L-NMMA (p = .004, all doses combined). Myocardial nitric oxide synthase activity was ranked as follows: nonsurvivors > survivors > noninfected controls (p < .01). Other tissues examined showed the same pattern. L-NMMA produced sustained increases in systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after the onset of infection (p < or = .04). Left ventricular ejection fraction was depressed by septic shock (p = .01) and further decreased by L-NMMA (p = .02). However, control and L-NMMA cardiac index values were similar (p > .4), perhaps because L-NMMA increased pulmonary artery occlusion pressure (p = .02). From 9 to 24 hrs, epinephrine, in the absence or presence of L-NMMA, blunted recovery of cardiac index (p < .02) and had a diminishing vasopressor effect (p = .05). Neither L-NMMA nor epinephrine, individually or combined, significantly altered survival rates at the doses investigated (p > or = .69).<br />Conclusions: The tested doses showed that nitric oxide production was inhibited by L-NMMA in canine septic shock, but mortality and myocardial depression were unaffected. These results suggest that if L-NMMA has a beneficial effect on survival rates in septic shock, it is small.
- Subjects :
- Animals
Dogs
Drug Combinations
Hemodynamics drug effects
Nitric Oxide biosynthesis
Nitric Oxide blood
Nitric Oxide metabolism
Nitric Oxide Synthase metabolism
Enzyme Inhibitors therapeutic use
Epinephrine therapeutic use
Escherichia coli Infections drug therapy
Nitric Oxide Synthase antagonists & inhibitors
Sepsis drug therapy
Vasoconstrictor Agents therapeutic use
omega-N-Methylarginine therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 0090-3493
- Volume :
- 26
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Critical care medicine
- Publication Type :
- Academic Journal
- Accession number :
- 9590318
- Full Text :
- https://doi.org/10.1097/00003246-199805000-00022