Increase in exhaled nitric oxide and protective role of the nitric oxide system in experimental pulmonary embolism.
OBJECTIVE
Pulmonary embolism (PE) represents a real diagnostic challenge. PE is associated with pulmonary hypertension due to pulmonary vascular obstruction and vasoconstriction. We recently reported that pulmonary gas embolism transiently increases exhaled nitric oxide (FENO), but it is not known whether solid emboli may alter FENO, and whether an intact endogenous NO synthesis has a beneficial effect in experimental solid pulmonary embolism.


METHODS
We used anaesthetised and ventilated rabbits in these experiments. To mimic PE, a single intravenous infusion of homogenized autologous skeletal muscle tissue (MPE) was given to rabbits with intact NO production (MPE of 60, 15, or 7.5 mg kg(-1); group 1) and to another group (group 2) with inhibited NO synthesis (L-NAME 30 mg kg(-1); MPE of 7.5, 15 or 30 mg kg(-1)).


RESULTS
In group 1, after MPE, FENO increased rapidly and dose-dependently and FENO was still significantly elevated after 60 min with the two highest emboli doses. All these animals survived more than 60 min after embolization. In group 2, MPE of 7.5, 15 and 30 mg kg(-1), in combination with NO synthesis inhibition, resulted in 67%, 50% and 25% survival at 60 min respectively, representing a statistically significant decrease in survival. Cardiovascular and blood-gas changes after MPE were intensified by pre-treatment with NO synthesis inhibitor.


CONCLUSIONS
We conclude that solid PE causes a sustained, dose-dependent increase in FENO, giving FENO a diagnostic potential in PE. Furthermore, intact NO production appears critical for tolerance to acute PE.
Nilsson
K F
KF
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden. kristofer.nilsson@ki.se
Gustafsson
L E
LE
Adding
L C
LC
Linnarsson
D
D
Agvald
P
P
D000758:Anesthesia; D000818:Animals; D001784:Blood Gas Analysis; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007262:Infusions, Intravenous; D018482:Muscle, Skeletal / Q000737:chemistry; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011655:Pulmonary Embolism / Q000378:metabolism* / Q000503:physiopathology*; D011817:Rabbits; D012121:Respiration, Artificial; D016019:Survival Analysis
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester