Pulmonary hypertension due to left heart disease causes intrapulmonary venous arterialization in rats

Objective: A rat model of left atrial stenosis-associated pulmonary hypertension due to left heart diseases was prepared to elucidate its mechanism.

Methods: Five-week-old Sprague-Dawley rats were randomly divided into 2 groups: left atrial stenosis and sham-operated control. Echocardiography was performed 2, 4, 6, and 10 weeks after surgery, and cardiac catheterization and organ excision were subsequently performed at 10 weeks after surgery.

Results: Left ventricular inflow velocity, measured by echocardiography, significantly increased in the left atrial stenosis group compared with that in the sham-operated control group (2.2 m/s, interquartile range [IQR], 1.9-2.2 and 1.1 m/s, IQR, 1.1-1.2, P < .01), and the right ventricular pressure-to-left ventricular systolic pressure ratio significantly increased in the left atrial stenosis group compared with the sham-operated control group (0.52, IQR, 0.54-0.60 and 0.22, IQR, 0.15-0.27, P < .01). The right ventricular weight divided by body weight was significantly greater in the left atrial stenosis group than in the sham-operated control group (0.54 mg/g, IQR, 0.50-0.59 and 0.39 mg/g, IQR, 0.38-0.43, P < .01). Histologic examination revealed medial hypertrophy of the pulmonary vein was thickened by 1.6 times in the left atrial stenosis group compared with the sham-operated control group. DNA microarray analysis and real-time polymerase chain reaction revealed that transforming growth factor-β mRNA was significantly elevated in the left atrial stenosis group. The protein levels of transforming growth factor-β and endothelin-1 were increased in the lung of the left atrial stenosis group by Western blot analyses.

Conclusions: We successfully established a novel, feasible rat model of pulmonary hypertension due to left heart diseases by generating left atrial stenosis. Although pulmonary hypertension was moderate, the pulmonary hypertension due to left heart diseases model rats demonstrated characteristic intrapulmonary venous arterialization and should be used to further investigate the mechanism of pulmonary hypertension due to left heart diseases.