A model of embolic chronic pulmonary hypertension in the dog

Abstract

Despite numerous efforts, a reliable model of chronic embolic pulmonary hypertension has not been established. To develop such a model five conscious mongrel dogs were embolized repeatedly over 16-30 wk with Sephadex microspheres 286 +/- 70 micron in diameter. Hemodynamic and respiratory measurements were obtained just prior to each embolization. Chronic pulmonary hypertension developed in all dogs. Pulmonary hypertension was not accounted for by increased cardiac output, wedge pressure, right atrial pressure, or systemic arterial pressure. Gas exchange was little altered. Lung histological study revealed microspheres clustered within vessels. In three dogs increased pulmonary arterial pressure was sustained despite cessation of embolization for up to 5 mo. Reembolization in one of these caused further pulmonary hypertension. In two dogs acute pulmonary vasodilation by O2 breathing and administration of prostaglandin E1 reduced, but did not abolish, the increased pulmonary vascular resistance, suggesting some vascular tone was present. An embolic model of chronic pulmonary hypertension in awake dogs allows further investigation into the evolution of pulmonary hypertension.

RhoA/Rho-kinase signaling: a therapeutic target in pulmonary hypertension

“…Another documented animal model of PAH involves the formation of chronic emboli in pulmonary vessels. Shelub et al induced chronic embolic PAH through repeated microembolizations with the injection of Sephadex ® microspheres 20. The utilization of this approach allows different-sized vessels to be targeted depending on the diameter size of the microspheres that are injected, and vascular obstruction and vasoconstriction are the primary mechanisms of the high pulmonary vascular resistance that occurs 20,21.…”

A Pulmonary Hypertension Model Induced by Continuous Pulmonary Air Embolization

“…A titratable infusion rate plus the long duration of insult enabled us to minimize animal death by preventing fatal events such as acute lung edema or acute heart failure that have been reported in previous studies [10,12]. Also, PaO 2 levels were maintained above 80 mmHg or higher through the experimental course.…”

“…Shelub et al [10], Weimann et al [12], and Sato et al [21] reported that recurrent microembolism with microspheres caused pulmonary hypertension. Unfortunately, a high mortality rate or a lack of histologic evidence of pulmonary vascular remodeling weakens the interpretation of these studies.…”

“…However, these models either showed only mild elevation of pulmonary pressure or inadequate morphological data of the lung and the right ventricle. Some models lack reproducibility due to high animal mortality [10,12]. The goal of the present study was to develop a reliable chronic pulmonary hypertension model in large animals by continuous pulmonary air embolization.…”

“…Previous chronic large animal models with embolization have been reported [10][11][12]. However, these models either showed only mild elevation of pulmonary pressure or inadequate morphological data of the lung and the right ventricle.…”