Precapillary pulmonary hypertension leads to reversible bronchial hyperreactivity in rats

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.

Prevention of bronchial hyperreactivity in a rat model of precapillary pulmonary hypertension

“…Due to this technical difficulty, technically acceptable Ppa recordings were possible only in about two-third of the rats. According to literature [11,13,20], we also noted an elevated systolic Ppa in the rats in Group CS, confirming the validity of the experimental model for investigation of the pulmonary consequences of chronic precapillary PHT. It is noteworthy, however, that the model applied here mimics clinical conditions encountered in patients with left-to-right shunts and increased pulmonary blood flow, and the results may not be extrapolated to other forms of PHT.…”

“…It was earlier reported [11] that the creation of an ACS led to precapillary PHT, which was associated with enhanced airway responsiveness to MCh. This experimental model has been extensively validated previously both by ourselves and by other research groups, and has been proved to provide an increased pulmonary blood flow leading to PHT [11-13,20].…”

“…This experimental model has been extensively validated previously both by ourselves and by other research groups, and has been proved to provide an increased pulmonary blood flow leading to PHT [11-13,20]. Precise measurement of the pulmonary haemodynamics in rats was complicated by the small size of the animal and the lack of catheter-tip balloon, which normally helps to introduce to the pulmonary artery.…”

“…The surgical induction of precapillary PHT was performed as described in detail previously [11-13]. Briefly, a midline abdominal incision was made in a sterile manner and the infra-renal portions of the abdominal aorta and inferior vena cava were exposed at the site where the two vessels share a common fascia.…”

“…We earlier reported a lung function impairment in a reproducible model of precapillary PHT following the creation of a shunt between the abdominal aorta and the vena cava in rats [11]. We also demonstrated that precapillary PHT leads to the development of bronchial hyperresponsiveness (BHR) to methacholine subsequent to the altered mechanical interdependence between the pulmonary vasculature and the respiratory tract.…”