Systemic lobar shunting induces advanced pulmonary vasculopathy

Objectives: We characterized the morphology and vasomotor responses of a lo calized, high-flow model of pulmonary hypertension. Methods: An end-to-side anastomosis was created between the left lower lobe pulmonary artery and the aorta in 23 piglets. Control animals had a thorac otomy alone or did not have an operation, Eight weeks later, hemodynamic me asurements were made. Then shunted and/or nonshunted lobes were removed for determination of vascular resistance and compliance by occlusion technique s under conditions of normoxia. hypoxia (FIO2 = 0.03), and inspired nitric oxide administration. Quantitative histologic studies of vessel morphology were performed. Results: Eighty-three percent of animals having a shunt survived to final s tudy, Aortic pressure, main pulmonary artery and wedge pressures, cardiac o utput, blood gases, and weight gain were not different between control pigs and those receiving a shunt. Six of 9 shunted lobes demonstrated systemic levels of pulmonary hypertension in vivo. Arterial resistance was higher (2 4.3 +/- 12.0 vs 1.3 +/- 0.2 mm Hg . mL(-1) . s(-1). P =.04) and arterial co mpliance was lower (0.05 +/- 0.01 vs 0.16 +/- 0.03 mL/mm Hg, P =.02) in shu nted compared with nonshunted lobes. Hypoxic vasoconstriction was blunted i n shunted lobes compared with nonshunted lobes (31 % +/- 13% vs 452% +/- 10 7% change in arterial resistance, during hypoxia, P <.001). Vasodilation to inspired nitric oxide was evident only in shunted lobes (34% +/- 6% vs 1.8 % +/- 8.2% change in arterial resistance during administration of inspired nitric oxide, P =.008). Neointimal and medial proliferation was found in sh unted lobes with approximately a 10-fold increase in wall/luminal area rati o. Conclusions: An aorta-lobar pulmonary artery shunt produces striking vascul opathy, The development of severe pulmonary hypertension within a short tim e frame, low mortality, and localized nature of the vasculopathy make this model highly attractive for investigation of mechanisms that underlie pulmo nary hypertension.