Hemodynamic response to norepinephrine with and without inhibition of nitric oxide synthase in porcine endotoxemia

The objective of this study was to determine the circuit and cardiac effect s of norepinephrine (NE) with and without endotoxin, and how these response s are modified by the inhibition of nitric oxide synthase (NOS). We anesthe tized eight pigs and instrumented them for measurements of cardiac output ( Q) arterial pressure (Part), and mean pulmonary arterial pressure (Ppa). We also placed a 40-ml balloon in the right atrium for transient obstruction of flow and measurement of the mean circulatory filling pressure (MCFP) and resistance to venous return (RVR). After baseline measurements, animals we re treated with 10 mu g/kg/h of Escherichia coli endotoxin. At 105 min the measurements were repeated. We then infused 12.5 mg/kg of N-G-nitro-L-argin ine methyl ester (L-NAME) for 10 min and repeated the measurements. At base line, at the end of endotoxin infusion, and after L-NAME infusion we infuse d 3, 9, and 27 mu g/min of NE for 10 min each, and recorded hemodynamic mea surements at each dose. NE shifted the venous return curve (i.e., increased MCFP) to the right without changing RVR, and increased cardiac output (CO) both at baseline and after endotoxin. Endotoxemia markedly flattened the d ose-response curves for the change in Part, Ppa, CO, and heart rate with NE . The peak response of Part to NE after endotoxemia was restored with L-NAM E, but the other dose-response curves were not affected. NE also did not sh ift the venous return curve after L-NAME. Furthermore, the increase in Part with NE was of shorter duration after L-NAME than in the baseline conditio n. In conclusion, NE shifts the venous return curve to the right and improv es CO in endotoxic and nonendotoxic conditions. Endotoxemia decreases the a rterial responsiveness to NE. L-NAME partly restored this loss of responsiv eness in arteries but not in the venous circulation.