Intragastric nitric oxide is abolished in intubated patients and restored by nitrite*

Abstract

Nitrite in saliva is reduced to nitric oxide (NO) in the acidic stomach, and this NO may serve gastroprotective functions. We studied intragastric NO levels in healthy controls and in intubated intensive care unit patients before and after supplementation with nitrite. Prospective observational study involving patients and controls. A mixed intensive care unit and a university laboratory. Eight healthy volunteers and ten intubated, mechanically ventilated intensive care unit patients. A tonometric catheter was first evaluated in vitro and then used for all NO measurements. In fasting controls, gastric NO levels were measured repeatedly during periods of saliva depletion and after an intragastric nitrite infusion. In patients, changes in levels of intragastric NO, nitrite in plasma and gastric juice, and S-nitrosothiols in gastric juice were measured in response to an intragastric nitrite infusion. The tonometric catheter had a recovery of 80% with a high intraclass and interclass correlation. Median baseline NO levels in healthy volunteers were 21.6 ppm (interquartile range, 11.4-22.3 ppm) and decreased by 90% to 3.3 ppm (2.0-5.2 ppm) during 25-50 mins of saliva depletion. The NO level was restored by an intragastric nitrite infusion. Baseline NO levels in patients were almost abolished (0.1 ppm [0.07-0.4 ppm]) but increased rapidly to 124 ppm (range, 65-180 ppm) during intragastric nitrite infusion. Nitrite levels in plasma increased from 0.18 +/- 0.03 to 1.3 +/- 0.2 microM (p < .01), and levels of S-nitrosothiols in gastric juice increased from 0.12 +/- 0.09 to 6.7 +/- 1.8 microM. Intragastric generation of NO requires continuous delivery of nitrite-containing saliva and is almost abolished in critically ill, intubated patients. Enteral supplementation with nitrite could however fully restore gastric NO levels. Future studies will reveal if low NO levels contribute to stress ulcers and gastric overgrowth of bacteria often seen in these patients and in turn if restoring gastric NO with nitrite could be a useful therapeutic approach.