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The article “Vascular Histomolecular Analysis By Sequential Endoarterial Biopsy in a Shunt Model of Pulmonary Hypertension” in Pulmonary Circulation, Volume 3, Number 1, January to March 2013, pp. 50-57 by Abraham Rothman, Robert G. Wiencek, William N. Evans, Humberto Restrepo, Valeri Sarukhanov, Erkki Ruoslahti, Roy Williams, and David Mann details how endoarterial biopsy provides a new method of assessing pulmonary vascular histology and gene expression in pulmonary arterial hypertension (PAH). Percutaneous pulmonary endoarterial biopsy coupled with histologic and molecular analysis represents a potential new paradigm for diagnosis and potential treatment of PAH. Histomolecular analysis could become a routine component of the diagnostic information obtained in patients with pulmonary vascular diseases at the time of cardiac catheterization. In addition to obtaining pressures, cardiac output, calculation of pulmonary vascular resistance, angiography and vasodilator testing, endoarterial biopsy with histologic and molecular analysis would add a whole new dimension of biologic information to aid in diagnosis and choice of therapy. This analysis could identify novel applications for existing and new PAH drugs. The detection of stage- and disease-specific variation in gene expression could lead to individualized therapies.
The paper “Hemodynamic and Histologic Characterization of a Swine (Sus scrofa domestica) Model of Chronic Pulmonary Arterial Hypertension (PAH)” in Comparative Medicne, Volume 61, Number 3, June 2011 , pp. 258-262(5) by Abraham Rothman, Robert G. Wiencek, Stephanie Davidson, William N Evans, Humberto Restrepo, Valeri Sarukhanov, Amanda Rivera-Begeman, and David Mann, describes the use of an experimental endoarterial biopsy catheter to describe the hemodynamic, angiographic, and histologic progression of a swine aortopulmonary shunt model of chronic pulmonary hypertension. The animal model described in this paper showed hemodynamic, angiographic, and histologic characteristics of chronic pulmonary arterial hypertension that mimicked the arterial pulmonary hypertension of systemic-to-pulmonary arterial shunts in humans. The use of the endoarterial biopsy catheter allowed for sequential pulmonary vascular biopsy procedures as the PAH model developed. This PAH large animal model can be used to test therapeutic agents or interventions at several hemodynamic and disease stages, including at baseline prior to shunt surgery, during the initial high-flow but low-pressure state, and during the development of PAH. Experimental data obtained using this and other models and application of an in vivo endoarterial biopsy technique may aid in understanding mechanisms and developing therapies for experimental and human pulmonary arterial hypertension.
An animal model of lung transplantation was created in order to determine if VCAM mRNA in pulmonary arterial biopsy samples could be a marker of transplant rejection. Please see Increased Expression of Endoarterial Vascular Cell Adhesion Molecule-1 mRNA in an Experimental Model of Lung Transplant Rejection: Diagnosis by Pulmonary Arterial Biopsy by A. Rothman, D. Mann et. al. Transplantation. Vol. 75, No. 7. April 15, 2003. This animal model was developed to demonstrate that endoarterial biopsy samples obtained in a lung transplant model of organ transplant rejection would show an increase in VCAM mRNA levels with increasing rejection. RT-PCR analysis of endoarterial biopsy specimens assessed the allo-immune response on the pulmonary vasculature, which is the first point of contact between the recipient’s immune system and the donor organ. Endoarterial biopsy samples could be useful in the surveillance and early diagnosis of lung transplant rejection.
An animal model of pulmonary hypertension was created by monthly infusions of ceramic microspheres to occlude pulmonary vessels and increase pulmonary arterial pressure. Please see Percutaneous Pulmonary Endoarterial Biopsy in an Experimental Model of Pulmonary Hypertension by A. Rothman, M.D., D. Mann et. al. Chest. Vol. 114, No. 1. July 1998: 241-250. This animal model was developed in order to test the safety and effectiveness of the device at elevated pressures and to study the progressive changes that occur in pulmonary vasculature through the use of a new tool, the endoarterial biopsy catheter.
The endoarterial biopsy catheter was tested in the pulmonary arteries of normotensive animals in order to determine initial feasibility, safety and effectiveness of the device at normal arterial pressures. Please see Transvenous Procurement of Pulmonary Artery Smooth Muscle and Endothelial Cells Using a Novel Endoarterial Biopsy Catheter in a Canine Model by A. Rothman, M.D., D. Mann et. al. Journal of American College of Cardiology. Vol. 27, No. 1. January 1996: 218-224.