title: Intrapulmonary shear stress enhancement: a new therapeutic approach in pulmonary arterial hypertension.
abstract: OBJECTIVE
  Pulmonary arterial hypertension (PAH) is a dysfunctional endothelium disease with increased pulmonary vascular resistance (PVR) and poor prognosis. Current therapies are still insufficient. Here we propose a new pulsatile device as a more effective tool for PAH management compared with traditional treatments.
  
  
  METHODS
  Twelve piglets (10.3 ± 3.8 kg) were given either intrapulmonary pulsatile [P (n = 6)] or nonpulsatile [NP (n = 6)] tadalafil treatment. After median sternotomy and heparin injection (250 IU/kg), both groups underwent aorto-pulmonary surgical shunt for 1 h. During a second 1 h period in group P, a catheter prototype, driven by a small ventilator, was introduced into the pulmonary trunk and pulsated intermittently at 110 bpm irrespective of heart rate (90.6 ± 10.74 bpm). In group NP, tadalafil was given orally (1 mg/kg).
  
  
  RESULTS
  Hemodynamics and cardiac output (CO) were significantly (p < 0.05) improved in group P compared with group NP: CO was 0.56 ± 0.0.26 versus 0.54 ± 0.11 (L/min), respectively. Mean pulmonary artery pressure (PAP) was decreased in group P compared with group NP: PAP was 9.6 ± 2.97 versus 32.2 ± 5.07, respectively. Vascular resistances (dynes.s.cm(-5)/kg) were significantly lower in group P versus group NP: pulmonary resistance was 85 ± 42.12 versus 478 ± 192.91 and systemic resistance was 298.8 ± 172.85 versus 1301 ± 615.79, respectively. Using Western blot analysis, endogenous NO synthase expression in PA segments was nonsignificantly (p > 0.05) greater in group P (0.81 ± 0.78) versus (0.62 ± 0.35) group NP.
  
  
  CONCLUSIONS
  Induced with an appropriate device, intrapulmonary shear stress-mediated endothelial function enhancement provides a more effective nearly physiological therapy for PAH.
authors.affiliation: Laboratory of Biosurgical Research (Alain Carpentier Foundation), Pompidou Hospital, University Paris Descartes, 75015, Paris, France. nourmd@mac.com
authors.forename: Sayed
authors.initials: S
authors.lastname: Nour
authors.forename: Gang
authors.initials: G
authors.lastname: Dai
authors.forename: Daniel
authors.initials: D
authors.lastname: Carbognani
authors.forename: Minze
authors.initials: M
authors.lastname: Feng
authors.forename: Daya
authors.initials: D
authors.lastname: Yang
authors.forename: Nermine
authors.initials: N
authors.lastname: Lila
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Chachques
authors.forename: Guifu
authors.initials: G
authors.lastname: Wu
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D002243:Carbolines / Q000494:pharmacology; D002302:Cardiac Output; D004195:Disease Models, Animal; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000379:methods*; D065627:Familial Primary Pulmonary Hypertension; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000503:physiopathology* / Q000601:surgery*; D052250:Nitric Oxide Synthase Type III / Q000097:blood; D033081:Shear Strength / Q000502:physiology*; D013552:Swine; D000068581:Tadalafil; D014655:Vascular Resistance
chemical_list: D015415:Biomarkers; D002243:Carbolines; D000068581:Tadalafil; D052250:Nitric Oxide Synthase Type III