title: Sildenafil selectively inhibits acute pulmonary embolism-induced pulmonary hypertension.
abstract: Selective pulmonary vasodilators attenuate acute pulmonary embolism (APE)-induced pulmonary hypertension. We examined the effects of intravenous sildenafil on the hemodynamic and respiratory changes caused by APE in anesthetized dogs. Sham operated animals (n=3) received only saline infusions. APE was induced by intravenous injections of microspheres in amounts adjusted to increase mean pulmonary artery pressures (MPAP) by 20 mmHg. Hemodynamic evaluation was performed and arterial blood samples were drawn for blood gas analysis at baseline, 15 and 30 min after APE was induced, and then 15, 30, and 45 min after the sildenafil infusion (1 mg kg(-1) infused intravenously in 15 min followed by 0.3 mg kg(-1) h(-1) for 30 min) started in the Sildenafil group (n=7), or saline infusion started in the control group (n=8). APE induced sustained pulmonary hypertension and 325% increase in pulmonary vascular resistance index (PVRI) without significant changes in the other hemodynamic parameters. While the animals in the control group showed no further changes in MPAP and PVRI, a significant decrease in MPAP and PVRI (-25 and -45%, respectively; P<0.05 both) was observed with sildenafil. No significant changes in the other hemodynamic parameters were observed in both groups. APE decreased PaO2, whereas sildenafil attenuated the decrease in PaO2 (P<0.05). We conclude that intravenous sildenafil can selectively attenuate the increases in MPAP and PVRI after APE.
authors.affiliation: Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, SP, Brazil.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Dias-Junior
authors.forename: Tadeu F
authors.initials: TF
authors.lastname: Vieira
authors.forename: Heitor
authors.initials: H
authors.lastname: Moreno
authors.forename: Paulo R
authors.initials: PR
authors.lastname: Evora
authors.forename: Jose E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D000818:Animals; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology*; D007262:Infusions, Intravenous; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011655:Pulmonary Embolism / Q000150:complications / Q000188:drug therapy*; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate