Effects of different inspired oxygen fractions on sildenafil-induced pulmonary anti-hypertensive effects in a sheep model of acute pulmonary embolism.
OBJECTIVE
Sildenafil is a pulmonary anti-hypertensive agent whose action could be modified by different fractions of inspired oxygen (FiO2). We compared the effects of pure oxygen (FiO2 > 90%) or room air (21% FiO2) on the cardiopulmonary actions of sildenafil in sheep with acute pulmonary embolism (APE).


METHODS
Thirty-two anesthetized, mechanically ventilated sheep (34.9 ± 5.4 kg), were randomly distributed into four groups (n = 8 per group): FiO2 > 90% without intervention; APE induced by microspheres with FiO2 > 90%, followed 30 min later by placebo (Emb90); or APE followed 30 min later by intravenous sildenafil (0.7 mg/kg over 30 min) with FiO2 > 90% (Emb + Sild90) or 21% FiO2 (Emb + Sild21) [Corrected]. Variables were recorded until 30 min after the end of treatment administration.


RESULTS
Microsphere injection increased (P < 0.05) mean pulmonary artery pressure (MPAP) in all embolized groups (111-140% higher than that of baseline). Compared with values recorded 30 min after induction of APE (E30), sildenafil induced greater decreases in MPAP in the Emb + Sil90 group than in the Emb + Sil21 group (23% and 14% lower than E30, respectively). Hypotension (mean arterial pressure < 60 mm Hg) was precipitated by sildenafil due to systemic vasodilation in the Emb + Sil21 group. Embolization lowered the PaO2/FiO2 ratio and increased venous admixture, but sildenafil did not alter the oxygenation impairment induced by APE.


CONCLUSIONS
Sildenafil induces a more consistent pulmonary anti-hypertensive effect and causes less interference with the systemic circulation with the concomitant use of pure oxygen than that with room air in the APE setting.
Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Diana Rocío Becerra
DR
Velásquez
Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil; Departamento de Anestesiologia, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Francisco José
FJ
Teixeira-Neto
Departamento de Anestesiologia, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Angie
A
Paola Lagos-Carvajal
Departamento de Anestesiologia, Faculdade de Medicina, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Miriely
M
Steim-Diniz
Departamento de Cirurgia e Anestesiologia Veterinária, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil.
Nathalia Celeita
NC
Rodríguez
Departamento de Farmacologia, Instituto de Biociências de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, São Paulo, Brazil. Electronic address: carlosjunior@ibb.unesp.br.
Carlos Alan
CA
Dias-Junior
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000503:physiopathology; D010100:Oxygen / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000503:physiopathology; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011687:Purines / Q000494:pharmacology; D015656:Respiratory Mechanics / Q000187:drug effects; D012756:Sheep; D000068677:Sildenafil Citrate; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D010879:Piperazines; D011687:Purines; D013449:Sulfonamides; D000068677:Sildenafil Citrate; D010100:Oxygen
Acute pulmonary embolism; Pulmonary hypertension; Sildenafil