Differential effects of inhaled and intravenous sildenafil in the prevention of the pulmonary endothelial dysfunction due to cardiopulmonary bypass.
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.
Aubin
Marie-Claude
MC
Department of Pharmacology, Université de Montréal, Montreal, Quebec, Canada.
Laurendeau
Steve
S
Mommerot
Arnaud
A
Lamarche
Yoan
Y
Denault
André
A
Carrier
Michel
M
Perrault
Louis P
LP
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*
D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D000068677:Sildenafil Citrate; D000109:Acetylcholine; D001920:Bradykinin