Received for publication November 10, 2004.
Revised May 4, 2005.
Accepted for publication May 4, 2005.

Transendocardial and trans-epicardial intramyocardial FGF-2 administration: Myocardial and Tissue Distribution

Abstract

Effective local delivery to the heart remains an obstacle to successful therapeutic application of a number of drugs and biological agents. This study was designed to study and optimize the delivery characteristics of trans-endocardial intramyocardial (IM) administration, determine myocardial deposition and retention over time, and compare it to trans-epicardial IM injection. Thirty-nine pigs were used for the study [15 for catheter optimization, 15 for trans-endocardial IM delivery, and 9 for trans-epicardial IM delivery). ¹²⁵I-FGF2 (25µCi) was used as prototype molecule. Tissue and myocardial distribution was determined at 1 and 24 hours and 7 days. Using 1-hour ¹²⁵I-FGF2 myocardial deposition as a parameter for delivery efficiency, the optimal needle length and delivery volume for transendocardial based delivery were determined to be 6-mm and 0.1-ml, respectively. Using these parameters for endocardial delivery, ¹²⁵I-FGF2 cardiac activity was 18.01±3.84% of delivered activity at 1-hour, 11.65±5.17% at 24-hours, and 2.32±0.87% at 7-days in ischemic animals. Studies in non-ischemic animals produced similar results. For trans-epicardial delivery, ¹²⁵I-FGF2 cardiac specific activity was 23.14±12.67% for the 6-mm needle, declining to 12.32±8.50% 24 hr and did not significantly differ from values obtained following trans-endocardial delivery. Thus, optimized trans-endocardial intramyocardial delivery using Biosense^R-guidance results in efficient delivery of FGF-2 to the target myocardium that is comparable to trans-epicardial delivery, both providing markedly higher myocardial deposition and retention and lower systemic recirculation of FGF-2 than intracoronary, intrapericardial, or intravenous delivery. However, myocardial distribution is limited to injection sites.

Key words: drug clearance, drug delivery, drug disposition, drug distribution, targeted delivery

This article has been cited by other articles:

				D. J. Chambers Editorial comment Eur. J. Cardiothorac. Surg., April 1, 2008; 33(4): 651 - 652. [Full Text] [PDF]

				P. Voisine, A. Rosinberg, J. J. Wykrzykowska, Y. Shamis, G. F. Wu, E. Appelbaum, J. Li, F. W. Sellke, D. Pinto, C. M. Gibson, et al. Skin-derived microorgan autotransplantation as a novel approach for therapeutic angiogenesis Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H213 - H219. [Abstract] [Full Text] [PDF]