PURPOSE: Diseases of the trachea and bronchi, including carcinoma, asthma and malacia, could potentially be treated with local, direct infusion of medications into the bronchial wall and adventitia. Cardiovascular adventitial drug delivery has shown circumferential and longitudinal distribution, but controlled and effective delivery and confirmation of cylindrical distribution in the bronchial adventitia has not been demonstrated. Our aim was to determine the ability of a micro-infusion catheter to target the bronchial adventitia and to measure distribution of bronchial adventitial infusions in vivo.
METHODS: The transbronchoscopic catheter (Blowfish(tm) Micro-Infusion Catheter, Mercator MedSystems, Inc.) deploys a fixed-length 35Ga needle perpendicularly into the bronchial wall. A porcine subject underwent flexible bronchoscopy with the catheter advanced through the working channel. Methylene blue and radiopaque contrast were infused to bronchial adventitia in volumes of 0.1ml (N=3), 0.3ml (N=7) or 1.0ml (N=3). Two needle lengths were tested: 0.9mm (6 infusions) and 1.2mm (7 infusions). X-ray fluoroscopy and bronchoscopy were used to confirm infusion success. The subject was sacrificed 1 hour after delivery. Formalin-fixed bronchi were cut into 2-4 mm thick rings with surrounding parenchymal tissue intact. Gross diffusion range was visually assessed for circumferential and longitudinal distribution.
RESULTS: One infusion with the 1.2mm needle was parenchymal based on X-ray fluoroscopic images and was excluded from analysis. Infusion volumes of 0.1ml, 0.3ml and 1.0ml resulted in methylene blue dye surrounding 67±29%, 55±17% and 80±20% of the infusion site circumference, with longitudinal distribution of 4.0±1.7mm, 8.1±4.1mm and 18.0±3.0mm, each respectively. No significant bleeding was seen during bronchoscopic observation.
CONCLUSION: This catheter is a new tool for localized drug delivery into the bronchial adventitia. Diffusion is positively correlated with infusion volume and primarily located in the bronchial wall and adventitia. Infusions of 1.0ml provided nearly circumferential coverage with effective longitudinal distribution within one hour of delivery.
CLINICAL IMPLICATIONS: Prevalence of bronchial diseases that may be treated with local drug delivery is substantial and growing. The development of local drug therapies for these diseases warrants further investigation.
DISCLOSURE: Armin Ernst, Grant monies (from sources other than industry) The project described was supported by Award Number R41CA141907 from the National Cancer Institute. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.; Shareholder Dr. Kirk Seward is a shareholder of Mercator MedSystems, Inc.; Employee Dr. Kirk Seward is President and Chief Technology Officer of Mercator MedSystems, Inc.; Fiduciary position (of any organization, association, society, etc, other than ACCP Dr. Kirk Seward is on the Board of Directors of Mercator MedSystems, Inc.; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. The Blowfish Micro-Infusion Catheter is not yet approved by the FDA.