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Lung volume reduction surgery in an animal emphysema model

Institution: University of California, Irvine
Investigator(s): Matthew Brenner, M.D.
Award Cycle: 2000 (Cycle 9) Grant #: 9RT-0094 Award: $456,336
Subject Area: Pulmonary Disease
Award Type: Research Project Awards
Abstracts

Initial Award Abstract
Emphysema is a severe and debilitating lung disease that results from smoking cigarettes. Patients with emphysema suffer from destruction of the lung tissue with symptoms of severe shortness of breath. The symptoms can progress to complete disability and death. Medical treatment of emphysema has little effect on disease symptoms or progression. Recently, new surgical techniques are being investigated to improve breathing function and symptoms for patients with severe emphysema. This surgery is called lung volume reduction surgery (LVRS) and involves removal of poorly functioning lung tissue. LVRS techniques must be improved in order to provide the greatest possible benefit and lowest possible risks to patients. Animal studies are needed in order to make substantial improvement in LVRS surgical treatments. We have developed animal models of emphysema that are very similar to human emphysema. We are studying lung volume reduction surgical techniques assessed using sophisticated heart and lung function measurement methods in these emphysematous animals. In accordance with the California TRDRP request for research into the effects of smoking and treatment of smoking related disease, we plan to study ways of substantially improving LVRS using this animal model.

There are a number of mechanisms by which LVRS effects lung function and symptoms in patients with emphysema. Some of the benefits from LVRS results from: 1) removal of poorly functioning areas of the lung, allowing more normal lung regions to expand and ventilate more effectively, 2) improving the balance between the regions of air flow and blood flow during breathing, 3) improving the position of the diaphragm, chest wall, and breathing muscles, and 4) tightening up loose lung tissue and allowing the lungs to exhale more quickly. The resistance slowing exhalation of emphysematous lungs can be improved following the LVRS surgery as well. Many of these effects are most noticeable during rapid breathing with exercise or stress.

LVRS involves removal of regions of poorly functioning lung regions. The major questions in this study involve finding the optimal amount of lung tissue to remove during surgery and the best methods for removal. Obviously, if too little lung tissue is removed, there will be no benefit from the surgery. If too much lung tissue is removed, there will be too little remaining lung to perform necessary breathing tasks. Therefore, methods need to be developed for optimizing the amount of lung tissue removal during LVRS.

Therefore, we will try to answer the following questions in this study: 1) What aspects of lung function (breathing rate, blood flow, or gas transfer) determine the preferred amount of lung to remove during LVRS? 2) What measures can be performed during surgery to guide the optimal extent of tissue removal for the surgeon? 3) What surgical techniques results in the greatest benefit and lowest risks from surgery (are staple tissue removal procedures, or combined staple and laser procedures preferable)? 4) Is it better to operate on one side at a time, or perform LVRS on both lungs simultaneously?

We will attempt to answer these questions using animal models of emphysema to determine the optimal LVRS response. The findings from this study should help improve surgical treatment for patients with severe emphysema. In addition, some patients with severe emphysema and lung cancer cannot be operated upon in attempt to cure their cancers because their lung function is too poor. By improving lung function with LVRS, many of these patients could then undergo surgery to potentially cure their lung cancer.
Publications

Pulmonary vascular pressures increase after lung volume reduction surgery in rabbits with more severe emphysema
Periodical: Journal of Surgical Research Index Medicus:
Authors: Powell LL, Ha HP, Serna D, et al ART
Yr: 2000 Vol: 92 Nbr: Abs: Pg: 157-164

The new NETT paradigm of health care financing agency sponsored clincal research trials: Advances and Dilemmas.
Periodical: Journal of Investigative Medicine Index Medicus:
Authors: Brenner M, Jones BU, Daneschvar HL, and Triff S ART
Yr: 2001 Vol: 7 Nbr: Abs: Pg:

Photodynamic therapy for patients with advanced non-small-cell carcinoma of the lung.
Periodical: Clinical Lung Cancer Index Medicus:
Authors: Jones BU, Helmy M, Brenner M, Serna DL, Williams J, Chen JC, and Milliken JC ART
Yr: 2001 Vol: 3 Nbr: 1 Abs: Pg:

NOn-invasive hemodynamic monitoring using near infrared frequency domain photon migration in rabbit hemorrhagic shock model.
Periodical: ATS/Respiratory and Critial Care Medicine Index Medicus:
Authors: Mina-Araghi R, Hanna N, Lee J, Cerussi A, Poggemeyer H, Krutzik M, Brenner M, et al. ABS
Yr: 2003 Vol: 167 Nbr: 7 Abs: Pg: A788

Optical coherence tomography of malignant hamster cheek pouches.
Periodical: ATS/Respiratory and Critial Care Medicine Index Medicus:
Authors: Brenner M, Mina Araghi R, Matheny E, Hanna N, Jung WG, Chen Z, Wilder-Smith P ABS
Yr: 2003 Vol: 167 Nbr: 7 Abs: Pg: A788

Evaluation of rabbit tracheal inflammation with optical coherence tomography.
Periodical: ATS/Respiratory and Critial Care Medicine Index Medicus:
Authors: Mina-Araghi R, Mahmood U, Han S, Jung WG, Chen Z, Poggemeryer H, Brenner M, et al. ABS
Yr: 2003 Vol: 167 Nbr: 7 Abs: Pg: A788

Evaluation of tracheal imaging by optical coherence tomography in multiple species.
Periodical: ATS/Respiratory and Critial Care Medicine Index Medicus:
Authors: Mina-Araghi R, Han S, Mahmood U, Jung WG, Chen Z, Krutzik M, Tran P, Brenner M, ABS
Yr: 2003 Vol: 167 Nbr: 7 Abs: Pg: A788

Optical coherence tomography of malignant hamster cheek pouches.
Periodical: Journal of Investigative Medicine Index Medicus:
Authors: Matheny E, Hanna N, Mina-Araghi R, Jung WG, Chen Z, Wilder-Smith P, Brenner M ABS
Yr: 2003 Vol: 51 Nbr: 1 Abs: Pg: S169

Non-invasive hemodynamic monitoring using near infrared frequency domain photon migration in rabbit hemorrhagic shock model.
Periodical: Journal of Investigative Medicine Index Medicus:
Authors: Hanna N, Mina-Araghi R, Lee J, Cerussi A, Poggemeyer H, Krutzik M, Jones B, Brenner M ABS
Yr: 2003 Vol: 51 Nbr: 1 Abs: Pg: S169

Evaluation fo tracheal imaging by optical coherence tomography in multiple species.
Periodical: Journal of Investigative Medicine Index Medicus:
Authors: Han S, Mahmood U, Mina-Araghi R, Jung Wg, Chen Z, Krutzik M, Walton R, Brenner M ABS
Yr: 2003 Vol: 51 Nbr: 1 Abs: Pg: S169

Evaluation of rabbit tracheal inflammation with optical coherence tomography.
Periodical: Journal of Investigative Medicine Index Medicus:
Authors: Mahmood U, Han S, Mina-Araghi R, Jung WG, Chen Z, Pggemeyer H, Brenner M, et al. ABS
Yr: 2003 Vol: 51 Nbr: 1 Abs: Pg: S16

Investigation of high resolution non-invasive optical coherence tomography imaging for airway and oral malignancy.
Periodical: TRDRP Annual Report to the State of California Legislature Index Medicus:
Authors: Brenner M, Mina R, Poggyemeyer H, Jung WG, Krutzik M, et al. ABS
Yr: 2002 Vol: Nbr: Abs: Pg: