TY - JOUR
T1 - Response of the septic vasculature to prolonged vasopressor therapy with N(ω)-monomethyl-l-arginine and epinephrine in canines
AU - Freeman, Bradley D.
AU - Zeni, Fabrice
AU - Banks, Steven M.
AU - Eichacker, Peter Q.
AU - Bacher, John D.
AU - Garvey, Edward P.
AU - Tuttle, Joel V.
AU - Jurgensen, Cynthia H.
AU - Natanson, Charles
AU - Danner, Robert L.
PY - 1998/5/19
Y1 - 1998/5/19
N2 - Objective: To investigate the effect of blocking nitric oxide production on cardiovascular function and survival in canine sep- tic shock treated with or without a conventional vasopressor. Design: Randomized, controlled trial. Setting: An animal research laboratory at the National Institutes of Health. Subjects: Sixty purpose-bred beagles. Interventions: Fibrin clots containing Escherichia coil were surgically placed into the peritoneal cavity. N(ω)- monomethyI-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr), epinephrine (1 μg/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. 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 in creases in systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after the onset of infection (p < .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 ≤ .69). 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.
AB - Objective: To investigate the effect of blocking nitric oxide production on cardiovascular function and survival in canine sep- tic shock treated with or without a conventional vasopressor. Design: Randomized, controlled trial. Setting: An animal research laboratory at the National Institutes of Health. Subjects: Sixty purpose-bred beagles. Interventions: Fibrin clots containing Escherichia coil were surgically placed into the peritoneal cavity. N(ω)- monomethyI-L-arginine (L-NMMA) 10 mg/kg followed by 0.5, 1.0, or 4.0 mg/kg/hr), epinephrine (1 μg/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. 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 in creases in systemic vascular resistance index and mean arterial pressure 9 and 24 hrs after the onset of infection (p < .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 ≤ .69). 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.
KW - Endotoxin
KW - Epinephrine
KW - Hemodynamics
KW - Nitric oxide
KW - Sepsis
KW - Septic shock
KW - Survival
KW - Tumor necrosis factor
UR - http://www.scopus.com/inward/record.url?scp=17344380897&partnerID=8YFLogxK
U2 - 10.1097/00003246-199805000-00022
DO - 10.1097/00003246-199805000-00022
M3 - Article
C2 - 9590318
AN - SCOPUS:17344380897
SN - 0090-3493
VL - 26
SP - 877
EP - 886
JO - Critical care medicine
JF - Critical care medicine
IS - 5
ER -