Segmental vascular resistance in postobstructive pulmonary vasculopathy

Abstract

Chronic unilateral pulmonary arterial ligation has been touted as a model of arteriopathy resulting in a tremendous increase in anastomotic bronchial flow (Qbr) via collaterals. To investigate its effects on the pulmonary vasculature, we ligated the left main pulmonary artery of seven dogs and 120 days later pump perfused their left lower lobes (LLL) via a cannula in the pulmonary artery at pulmonary arterial flow (Qpa) of 250 ml/min. We measured Qbr (330 ml/min) and compared LLL with control contralateral right lower lobes (RLL) and three LLL from normal dogs. Pressure-flow (P-Q) curves were obtained by varying Qpa. With arterial and venous occlusion we measured total, arterial, venous, and middle segment resistances under baseline conditions, after serotonin and histamine, either with or without Qpa and with antegrade and retrograde Qbr. Light microscopy was done postmortem. The slope of the P-Q curve was 33.4 mmHg.l-1.min in the ligated lobes compared with 15.9 in the controls, attributable by the occlusion technique mainly to a rise in arterial resistance (22.4 mmHg.l-1.min compared with 7.4 in the controls) with a small rise in venous resistance. This was explained by significant arterial medial muscle thickening and some loss of LLL volume. The arterial segment was markedly hypersensitive to serotonin, and the venous segment was mildly hypersensitive to histamine compared with controls. The occlusion data also enabled us to model the point of entry of the bronchial circulation into the pulmonary circuit at the precapillary level and to calculate bronchial vascular resistance. We conclude that postobstructive vasculopathy substantially raises pulmonary vascular resistance, mainly upstream from the site of entry of the bronchial circulation. The role of the latter may be to keep it from rising excessively in the segments it perfuses, i.e., the middle and venous ones.

Bronchial circulation angiogenesis in the rat quantified with SPECT and micro-CT

“…In addition, an increase in systemic perfusion of the lung from 0.2% of the cardiac output to ∼ 5% was measured in mice using colored microspheres injected intravenous and intraaortic [19]. Similar results were also obtained in dogs where an increase in perfusion of up to 30% was measured using direct flow measurement techniques [13]. However, specific information on the extent and time course of the development of the bronchial circulation has not previously been presented, yet will be important for designing protocols for delivery of anti-cancer drugs.…”

“…After ligation of the left pulmonary artery (LPA), the bronchial circulation of the left lung has been shown to develop in sheep [3], dogs [10][11][12][13][14], rats [15][16][17][18], and mice [19,20] in an attempt to compensate for the lack of perfusion via the pulmonary circulation. Commonly, ligation of the LPA has been used because it is generally more accessible than the right lung, and in the rat, the left lung accounts for only one third of the total lung capacity, which can be partially compensated for by the right lung.…”

Chemokines as mediators of angiogenesis

“…The human lung is supplied by both the pulmonary and the bronchial circulation. Neovascularization and development of anastamoses between these circuits control pulmonary vascular resistance, necessary to maintaining blood flow to the metabolically active lung tissue in the context of injury and repair (78)(79)(80)(81). Compensatory neovascularization of up to 30% of the original pulmonary blood flow can occur in the bronchial circulation in all mammals in response to marked increases in pulmonary vascular resistance (81), and the mouse systemic circulation can supply 15% of the pulmonary flow within days after pulmonary artery ligation, a process that is associated with up-regulation of ELR+ CXC chemokines but not VEGF (82,83).…”

Inhibition of CXCR2attenuates bronchial angiogenesis in the ischemic rat lung

“…It normally provides less than 1% of cardiac output to the lung but has been shown to increase to as much as 30% of the original pulmonary blood flow after chronic unilateral pulmonary artery obstruction (13). This pathological feature of bronchial angiogenesis occurs during conditions of chronic inflammation such as cystic fibrosis (4), asthma (12), pulmonary fibrosis (27), lung cancer (16), and chronic thromboembolic disease (18).…”

“…This pathological feature of bronchial angiogenesis occurs during conditions of chronic inflammation such as cystic fibrosis (4), asthma (12), pulmonary fibrosis (27), lung cancer (16), and chronic thromboembolic disease (18). In animal models, pulmonary ischemia resulting from chronic pulmonary artery obstruction has been shown to cause proliferation of the systemic circulation to the lung in sheep (5), pigs (8), dogs (13), rats (28), and mice (14). However, little is known regarding the mechanisms that promote growth of bronchial arteries in chronic ischemia because most studies have focused on acute reperfusion injury or chronic pulmonary hypertension (8,20).…”