Establishment of canine pulmonary hypertension with dehydromonocrotaline. Importance of larger animal model for lung transplantation

Abstract

Single lung isografting in rats with pulmonary hypertension has been reported. However, it is hard to evaluate cardiopulmonary hemodynamics accurately or to use circulatory assists during procedures using rats. Therefore, we tried to establish a model of pulmonary hypertension in the beagle. Twenty young beagles were randomized into 3 groups. An injection of dehydromonocrotaline of 1.5 mg/kg (group 1, n = 7), 3.0 mg/kg (group 2, n = 10), or 4.5 mg/kg (group 3, n = 3) was performed via the right atrium. Two dogs in group 2 and all the dogs in group 3 died of acute pulmonary edema. During the 8 weeks after injection, the systolic pulmonary arterial pressure and pulmonary vascular resistance index increased significantly in group 2 from 21 +/- 2 to 56 +/- 9 mmHg and from 106 +/- 39 to 826 +/- 176 dynes.sec.cm-5.m2, respectively (P < 0.01). The changes in group 1 were less pronounced. The dogs in group 2 also had a rise in their plasma endothelin-1. Pathologic analysis revealed thickening of the media in small pulmonary arteries and hypertrophy of the right ventricular myocardium. Our data indicate that beagles treated with 3.0 mg/kg dehydromonocrotaline produced a unique, relatively noninvasive model of pulmonary hypertension. In the model, right ventricular failure prevented us from clamping one pulmonary artery. These relatively large animals with pulmonary hypertension will be valuable for further studies of lung transplantation.