Intrapulmonary shear stress enhancement: a new therapeutic approach in pulmonary arterial hypertension

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.

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).

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.

Induced with an appropriate device, intrapulmonary shear stress-mediated endothelial function enhancement provides a more effective nearly physiological therapy for PAH.