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Updated: Jun 14, 2026

Establishment and Validation of a Rat Model of Pulmonary Arterial Hypertension Associated with Pulmonary Fibrosis
Published on: May 23, 2025
Precapillary pulmonary hypertension leads to reversible bronchial hyperreactivity in rats
Britta S von Ungern-Sternberg1, Walid Habre, Adrian Regli
1Pediatric Anesthesia Unit, Geneva Children's Hospital, Geneva, Switzerland.
Abstract:
Congenital heart disease with left-to-right shunt may lead to precapillary pulmonary hypertension (PREPHT) with potential lung function impairment. The authors investigated the effects of PREPHT on lung responsiveness in a rat model of PREPHT by creating and repairing an abdominal aortocaval shunt (ACS). Rats were studied 4 weeks after the induction of ACS, and 4 weeks after its surgical repair. Control rats underwent sham surgery. To assess bronchial hyperreactivity, airway resistance (Raw) was measured at baseline and after increasing doses of methacholine. Raw was estimated by model fitting of the mechanical impedance of the respiratory system generated by forced oscillation technique. Lung morphological changes were assessed by histology. The prolonged presence of the ACS led to only minor changes in the basal respiratory mechanics, whereas it induced marked bronchial hyperreactivity, the methacholine-induced elevations in Raw being 49% +/- 5% before and 232% +/- 32% (P <.001) after ACS. These alterations were not associated with any changes in lung histology and were completely reversible on closure of the shunt. These results suggest that the induction of chronic increases in pulmonary blood flow and pressure causes reversible bronchial hyperreactivity. This may be consequent to the altered mechanical interdependence between the pulmonary vasculature and the respiratory tract.
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