PURPOSE: This study establishes a new model of sustained pulmonary hypertension induced by recurrent microembolism in pigs and evaluates the effects of nitric oxide (NO) inhalation in this model. MATERIALS AND METHODS: Fourteen pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of 7 weeks. Four pigs served as untreated controls. Hemodynamic and gas exchange measurements were performed on days 1 and 7 after the last embolization. RESULTS: Recurrent microembolism caused sustained pulmonary hypertension (mean pulmonary artery pressure [MPAP] 26 +/- 2 and 18 +/- 1 mm Hg on days 1 and 7, respectively) compared with the control group (MPAP 13 +/- 1 mm Hg each for days 1 and 7; P < .05, respectively). Right heart hypertrophy was present at autopsy as indicated by an increase in minimal myocyte diameter. Inhaled NO (5 and 40 parts per million [ppm]) was administered on days 1 and 7. On both days, inhaled NO significantly reduced MPAP and pulmonary vascular resistance without affecting systemic hemodynamics. There were no differences in responses to 5 and 40 ppm inhaled NO. CONCLUSION: We conclude that recurrent microembolization in pigs provides a reliable model of sustained pulmonary hypertension. In this model inhaled NO is a selective pulmonary vasodilator, indicating that active vasoconstriction significantly contributes to sustained pulmonary hypertension after recurrent microembolism.
PURPOSE: This study establishes a new model of sustained pulmonary hypertension induced by recurrent microembolism in pigs and evaluates the effects of nitric oxide (NO) inhalation in this model. MATERIALS AND METHODS: Fourteen pigs were embolized under general anesthesia with 300-microm microspheres intravenously three times over a period of 7 weeks. Four pigs served as untreated controls. Hemodynamic and gas exchange measurements were performed on days 1 and 7 after the last embolization. RESULTS: Recurrent microembolism caused sustained pulmonary hypertension (mean pulmonary artery pressure [MPAP] 26 +/- 2 and 18 +/- 1 mm Hg on days 1 and 7, respectively) compared with the control group (MPAP 13 +/- 1 mm Hg each for days 1 and 7; P < .05, respectively). Right heart hypertrophy was present at autopsy as indicated by an increase in minimal myocyte diameter. Inhaled NO (5 and 40 parts per million [ppm]) was administered on days 1 and 7. On both days, inhaled NO significantly reduced MPAP and pulmonary vascular resistance without affecting systemic hemodynamics. There were no differences in responses to 5 and 40 ppm inhaled NO. CONCLUSION: We conclude that recurrent microembolization in pigs provides a reliable model of sustained pulmonary hypertension. In this model inhaled NO is a selective pulmonary vasodilator, indicating that active vasoconstriction significantly contributes to sustained pulmonary hypertension after recurrent microembolism.
Authors: Maria E Campian; Maxim Hardziyenka; Martin C Michel; Hanno L Tan Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2006-09 Impact factor: 3.000
Authors: Jaume Aguero; Kiyotake Ishikawa; Kenneth M Fish; Nadjib Hammoudi; Lahouaria Hadri; Ana Garcia-Alvarez; Borja Ibanez; Valentin Fuster; Roger J Hajjar; Jane A Leopold Journal: PLoS One Date: 2015-04-29 Impact factor: 3.240
Authors: Frédéric Perros; Maria-Rosa Ghigna; Fanny Loisel; Denis Chemla; Benoit Decante; Vincent de Montpreville; David Montani; Marc Humbert; Elie Fadel; Olaf Mercier; David Boulate Journal: Biomedicines Date: 2020-11-11