Vascular growth and remodeling in compensatory lung growth following right lobectomy

Abstract

Studies in animal models have shown that, following lobectomy (LBX), there is compensatory growth in the remaining lung. The vascular growth response following right LBX (R-LBX) is poorly understood. To test the hypothesis that arterial growth and remodeling occur in response to LBX, in proportion to the amount of right lung tissue removed, two (24% of lung mass; R-LBX2 group) or three right lobes (52% of lung mass; R-LBX3 group) were removed via thoracotomy from adult rats. Sham control animals underwent thoracotomy only. Arteriograms were generated 3 wk after surgery. The areas of the left lung arteriogram, arterial branching, length of arterial branches, arterial density, and arterial-to-alveolar ratios were measured. To determine whether R-LBX causes vascular remodeling and pulmonary hypertension, muscularization of arterioles and right ventricular hypertrophy were assessed. Lung weight and volume indexes were greater in R-LBX3. Arterial area of the left lung increased 26% in R-LBX2 and 47% in R-LBX3. The length of large arteries increased in R-LBX3 and to a lesser extent in R-LBX2. The ratio of distal pulmonary arteries to alveoli was similar after R-LBX2 compared with sham but was 30% lower in R-LBX3. Muscularization of arterioles increased after R-LBX3, but not in R-LBX2. Right ventricular hypertrophy increased 50-70% in R-LBX3, but not in R-LBX2. Whereas removal of three right lung lobes induced arterial growth in the left lungs of adult rats, which was proportionate to the number of lobes removed, the ratio of distal pulmonary arteries to alveoli was not normal, and vascular remodeling and pulmonary hypertension developed.

Vascular endothelial growth factor accelerates compensatory lung growth after unilateral pneumonectomy

“…Support for the role of angiogenesis in the development of lung tissue can be found in studies showing that the anti-angiogenic agents fumagillin, thalidomide, and SU-5416 attenuate vascular growth and reduce alveolarization in developing rat lung (15). Additionally, it has been shown that compensatory vascular growth in lung tissue is proportional to the amount of tissue removed during pneumonectomy (21). Taken together, this research suggests a significant role for angiogenesis in both the normal development and compensatory growth of the lung.…”

Compensatory Lung Growth After Pneumonectomy

“…When a bilobectomy was performed in rats (24% of lung tissue removed), the arterial area of the remaining lung increased by 26% compared to sham animals. Furthermore, when lung resection was more extensive (trilobectomy, 52%) we found that the increase in arterial area increased by 47% (Le Cras, et al, 2005). Other researchers have shown the effects of exogenous angiogenic factors, such as vascular endothelial growth factor (VEGF) in the mouse model.…”

“…Our laboratory has shown that angiogenesis is necessary for successful CLG by demonstrating that angiogenesis inhibitors such as fumagillin or thalidomide prevented increased lung weight and volume after pneumonectomy (Maxey, et al, 2003). We have also shown that pneumonectomy induces arterial growth including the increase in length and number of branches of pulmonary arteries and that these changes are proportional to the amount of tissue removed (Le Cras, et al, 2005). When a bilobectomy was performed in rats (24% of lung tissue removed), the arterial area of the remaining lung increased by 26% compared to sham animals.…”

Vascular Endothelial Growth Factor Isoform and Receptor Expression During Compensatory Lung Growth

“…1). Arterial density, length, and surface area increase as blood flow to the remaining lung doubles [3,27,28]. Compensatory lung growth cannot occur without appropriate generation of functional gasexchange regions, which also requires significant and immediate peripheral blood vessel growth.…”