Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lu ng ischemia-reperfusion (YR)-induced injuries. We studied the role of iNO ( 10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 +/- 522 to 615 +/- 105 mu l and prevented the increase in lung wet-t o-dry weight ratio. To study the mechanisms of this prevention, we evaluate d the role of nitric oxide (NO) transport and lung exposure with matched ex periments by using either lungs or blood of animals exposed to iNO and bloo d or lungs of naive animals, iNO-exposed blood with naive lungs did not lim it the extravascular albumin accumulation (2,561 +/- 397 mu l), but iNO-exp osed lungs showed a leak not significantly different from the group in whic h both lungs and blood were iNO exposed (855 +/- 224 vs. 615 +/- 105 mu l). An improvement in heart I/R left ventricular developed pressure in the ani mals exposed to iNO showed that blood-transported NO was, however, sufficie nt to trigger remote organ endothelium and reduce the consequences of a del ayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based. on tissue or endothelium triggering.