title: Differential effects of inhaled and intravenous sildenafil in the prevention of the pulmonary endothelial dysfunction due to cardiopulmonary bypass.
abstract: The objective of the present study was to evaluate the effects of inhaled and intravenous sildenafil on the pulmonary endothelium-dependent relaxations, the hemodynamic profile and oxygenation after cardiopulmonary bypass. Five groups of Landrace swine were compared: 1) control; 2) cardiopulmonary bypass: 90 min of normothermic cardiopulmonary bypass; 3) precardiopulmonary bypass sildenafil nebulization; 4) postcardiopulmonary bypass sildenafil nebulization; 5) intravenous sildenafil administration prior to cardiopulmonary bypass. All groups underwent a 60-min period of pulmonary reperfusion after cardiopulmonary bypass. Vascular reactivity of second-degree pulmonary arteries was evaluated in response to acetylcholine and bradykinin. Cardiopulmonary bypass caused a significant decrease in endothelium-dependent relaxations to both agonists; this dysfunction was prevented by administration of sildenafil, both intravenous and inhaled (P < 0.05). Both administration routes prevented the significant increase in mean pulmonary arterial pressure with a safe hemodynamic profile. Moreover, intravenous and inhaled sildenafil after cardiopulmonary bypass also prevented the increase in alveoloarterial gradient (P < 0.05). Both sildenafil formulations of administration prevent the occurrence of pulmonary endothelial dysfunction. Depending on the administration moment and the route, the administration of sildenafil improves the hemodynamic profile and post-cardiopulmonary bypass oxygenation.
authors.affiliation: Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Aubin
authors.forename: Steve
authors.initials: S
authors.lastname: Laurendeau
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mommerot
authors.forename: Yoan
authors.initials: Y
authors.lastname: Lamarche
authors.forename: André
authors.initials: A
authors.lastname: Denault
authors.forename: Michel
authors.initials: M
authors.lastname: Carrier
authors.forename: Louis P
authors.initials: LP
authors.lastname: Perrault
mesh_terms: D000109:Acetylcholine; D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008171:Lung Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000109:Acetylcholine; D001920:Bradykinin