Effects of nitric oxide synthase inhibition on the cardiovascular response to low output shock.
OBJECTIVE
To study the role of nitric oxide in the cardiovascular response to a model of a low output syndrome.


METHODS
Prospective animal study.


METHODS
Animal research laboratory.


METHODS
Sheep anesthetized with pentobarbital, mechanically ventilated, and monitored with pulmonary arterial and peripheral arterial catheters.


METHODS
A low output state was induced by inflating a balloon-tip catheter placed in the right atrium. Cardiac index was maintained at 1 L/min/m2 throughout the experiment in three groups of sheep: a) control (n=6) b)LNNA group (pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine [LNNA, 100 mg/kg, iv bolus, n=6); and c) dexamethasone group (pretreated with dexamethasone (6 mg/kg, intravenous bolus, n=6). Dexamethasone is an inhibitor of the induction of nitric oxide synthase. LNNA or dexamethasone were administered 15 mins before inducing the low output state.


RESULTS
Hemodynamic and oxygen transport variables, and plasma lactate and pyruvate concentrations, were measured at baseline and during the next 3 hrs. For a comparable decrease in cardiac index and oxygen delivery in all groups, the LNNA group had less hypotension and a more marked increase in systemic vascular resistance as compared with the control group. Oxygen consumption and oxygen extraction were higher in the LNNA group as compared with the control group at 30 and 60 mins. Plasma lactate concentration increased significantly less in the LNNA group than in the control and the dexamethasone groups during the observation period.


CONCLUSIONS
Inhibition of nitric oxide synthesis during a severe low output state in sheep is associated with a better hemodynamic response, as evidenced by a greater vasoconstriction, and signs of less marked tissue hypoxia. It is likely that inhibition of nitric oxide synthesis in this model leads to an imbalance between the tonic relaxing action of nitric oxide and the influences of vasoconstrictor agents.
Lorente
J A
JA
Hospital Ramón y Cajal, Madrid, Spain.
Landin
L
L
Cañas
P
P
Delgado
M A
MA
Albaya
A
A
Renes
E
E
Jorge
P
P
Liste
D
D
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002303:Cardiac Output, Low / Q000150:complications / Q000201:enzymology / Q000503:physiopathology*; D002319:Cardiovascular System / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D004195:Disease Models, Animal; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000187:drug effects; D019335:Nitroarginine; D011446:Prospective Studies; D012756:Sheep; D012770:Shock, Cardiogenic / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology*
D019335:Nitroarginine; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase