Nitric oxide metabolism in canine sepsis: relation to regional blood flow

Purpose: To investigate the role of nitric oxide (NO) in early endotoxemia on the systemic and regional blood flow by measuring the plasma nitrite/nitrate (NOx) and blood nitrosyl-hemoglobin (NO-Hb) levels. Materials and Methods: This was a prospective, controlled, experimental study conducted in an animal research laboratory on 15 male mongrel dogs. Escherichia coli endotoxin (1 mg/kg) was injected intravenously. Results: Hepatic, renal, and iliac blood flow and cardiac output (CO) were measured before and 15, 30, 45, 90 and 180 minutes after injection of Escherichia coli endotoxin (1 mg/kg) (n = 6). NOx efflux from the organs was calculated by measuring plasma NOx levels. The arterial blood levels of NO-Hb were also measured (n = 4). As control studies, blood samples from dogs (n = 5) without exposure to endotoxin were assayed at 180 minutes for NOx and NO-Hb. Following endotoxin injection, mean arterial pressure decreased and reached its lowest value at 90 minutes (baseline vs. 90 minutes: 119.1 ± 5.8 vs. 82.5 ± 16.7 mm Hg, P < .0001). Hepatic artery bloodflow increased significantly (baseline vs. 180 minutes: 23.6 ± 12.0 vs. 170.0 ± 68.4 mL/min, P < .0001). There were no significant changes in plasma levels of NOx, uptake or release of NOx across the measured vascular beds, NO-Hb levels at anytime point. In the portal system, the portal vein flow correlated with NOx release (R = 0.69, P < .0001). Conclusion: In the early phase of endotoxemia in the dog, the significant reduction in systemic vascular resistance and hepatic arterial resistance are not associated with any measurable NOx release in the systemic circulation or the liver.