Molecular and functional mechanisms of right ventricular adaptation in chronic pulmonary hypertension

Background. Chronic pulmonary hypertension can lead to compensatory changes in the right ventricle. In this study, the adaptive mechanisms of the righ t ventricle in the setting of pulmonary hypertension were assessed at the m olecular and functional level using a canine model of monocrotaline pyrrole -induced pulmonary hypertension. Methods. Animals underwent pulmonary artery catheterization to measure pulm onary hemodynamics before and 8 weeks after an injection of monocrotaline p yrrole, 3 mg/kg (n = 8) or placebo (n = 8) (controls). Systolic function wa s assessed with load-insensitive means (preload-recruitable stroke work). M yocardial biopsy specimens were collected to analyze membrane alpha(1)- and beta-adrenergic receptor density and adenylate cyclase activity. Results. Eight weeks after injection, significant increases in pulmonary he modynamic indices were noted in monocrotaline-injected dogs. Significant in creases in right ventricular preload-recruitable stroke work were also obse rved in these animals compared with controls and occurred in association wi th significant increases in right ventricular alpha(1)- and beta-adrenergic receptor density and isoproterenol hydrochloride-stimulated adenylate cycl ase activity. No significant differences in basal adenylate cyclase activit y in the right ventricle were noted between the two groups. Conclusions. These data suggest that alterations in right ventricular funct ion in the setting of chronic pulmonary hypertension may partially be due t o changes in myocardial adrenergic receptor signaling. (Ann Thorac Surg 199 9;67:1053-8) (C) 1999 by The Society of Thoracic Surgeons.