CardiothoracicA Pulmonary Hypertension Model Induced by Continuous Pulmonary Air Embolization
Introduction
Clinically, pulmonary hypertension is defined as a sustained elevation of mean pulmonary arterial pressure to greater than 25 mm Hg at rest [1]. Pulmonary hypertension is characterized by progressive remodeling of the small pulmonary arteries, which promotes an increase in pulmonary arterial pressure and pulmonary vascular resistance, ultimately leading to right heart hypertrophy and failure. Idiopathic pulmonary arterial hypertension is rare with an extremely poor prognosis. Pulmonary hypertension presents more often associated with a common sequela of chronic lung conditions, especially chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis [2]. Regardless of advances in pharmaceutical therapy, pulmonary hypertension remains progressive and incurable 3, 4, 5, 6, 7. Medications have improved the quality of life for these patients, but many patients still require lung transplant. In 2007, emphysema and idiopathic pulmonary fibrosis accounted for more than 60% of lung transplants performed [8]. Also, pulmonary hypertension is one of the indications for lung transplant in patients with cystic fibrosis, another leading diagnosis group [9].
The role of a thoracic artificial lung in patients with pulmonary hypertension is unknown. An artificial lung may serve as a bridge until lung transplant is available. The function of the artificial lung in a setting of true clinical pulmonary hypertension and the effect of the high pulmonary vascular resistance on device function has not been adequately studied. A large animal model of chronic pulmonary hypertension is needed to evaluate the efficacy of an artificial lung device in this disease state.
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. 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.
Section snippets
Animal Preparation
All experimental procedures and protocols used in this study were reviewed and approved by the Institutional Animal Care and Use Committee (IACUC) of the University of Texas Medical Branch at Galveston, TX. Animals were handled in accordance with the Guide for the Care and Use of Laboratory Animals as adopted by the National Institutes of Health. Animal management protocol adherence was monitored daily by Animal Resource Center personnel with no conflict of interest. The animals were studied in
Hemodynamics
Figure 1 and Table 1 show hemodynamic changes. Following initiation of continuous air embolization, systemic arterial pressure was stable except for a slight decline at week 8 (P < 0.05), while pulmonary artery pressure in all the animals rose gradually but steadily (Fig. 1). At the end of wk 1, average MPAP reached 19.3 ± 0.5 mmHg, which was significantly higher than at baseline (13.8 ± 0.8 mmHg, P < 0.01). In individual sheep, the MPAP met pulmonary hypertension criteria (25 mmHg at rest)
Discussion
In this study, we developed a model of sustained chronic pulmonary hypertension in sheep by administering 8 wk of continuous air embolization into the pulmonary artery. All the animals completed the study. Pulmonary arterial pressure began to rise in the first wk of air embolization, was above 25 mmHg by wk 5 in all animals, and increased to 2.7-fold of baseline values by the end of wk 8. Pulmonary arterial pressure remained elevated for 1 wk after discontinuation of air embolization. Likewise,
Acknowledgment
The authors gratefully acknowledge the support of Shriners Hospital grant no. 8700 for funding this research.
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