Exhaled nitric oxide before and after cardiac surgery with cardiopulmonary bypass--response to acetylcholine and nitroglycerin.
BACKGROUND
Pulmonary endothelial dysfunction may occur after ischaemia-reperfusion injury and can be revealed as a reduced vasodilatory response upon administration of acetylcholine (ACh). ACh also releases the endothelium-derived vasodilator nitric oxide but direct measurements of this gas are difficult to perform in vivo. We wanted to study the effects of i.v. administration of ACh and the endothelium-independent vasodilator nitroglycerin on exhaled nitric oxide in relation to pulmonary endothelial dysfunction after open-heart surgery and cardiopulmonary bypass (CPB).


METHODS
Basal exhaled nitric oxide and the response in exhaled nitric oxide to i.v. injections of ACh and nitroglycerin were measured with chemiluminescence in 10 patients before and after open-heart surgery.


RESULTS
Exhaled nitric oxide decreased significantly after CPB. I.V. bolus injections of ACh induced a reproducible and dose-dependent increase in exhaled nitric oxide that was unaltered after CPB. In contrast, the increase in exhaled nitric oxide evoked by nitroglycerin was attenuated after CPB. The response in pulmonary vascular resistance index (PVRI) to an infusion of ACh decreased after CPB, indicating endothelial dysfunction. The decrease in PVRI response to ACh correlated to the duration of CPB.


CONCLUSIONS
Interestingly, pulmonary vascular dysfunction after CPB was accompanied by a reduction in the exhaled nitric oxide response to nitroglycerin and lower levels of basal exhaled nitric oxide. The ACh-induced responses in exhaled nitric oxide were unchanged, which could indicate nitric oxide-independent mechanisms behind the endothelial dysfunction in this study. The possibility of using exhaled nitric oxide dynamics to investigate pulmonary endothelial dysfunction merits further studies.
Törnberg
D C
DC
Department of Surgical Sciences, Anaesthesiology and Intensive Care, Karolinska Institute and Karolinska University Hospital Solna, S-171 76 Stockholm, Sweden. danieltornberg@hotmail.com
Angdin
M
M
Settergen
G
G
Liska
J
J
Lundberg
J O
JO
Weitzberg
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D005996:Nitroglycerin / Q000494:pharmacology; D011183:Postoperative Complications / Q000378:metabolism* / Q000503:physiopathology; D011651:Pulmonary Artery / Q000503:physiopathology; D015427:Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D015415:Biomarkers; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005996:Nitroglycerin; D000109:Acetylcholine