Publications

Percutaneous Intramyocardial Delivery is an Efficient Modality for Local Myocardial Treatment

Mehrdad Rezaee, Alan C Yeung, Peter Altman, Takeshi Suzuki, Dieter Lubbe, Robert S Schwartz, Simon H Stertzer, John D Altman

Background: Therapeutic angiogenesis requires the induction and recruitment of new blood vessel formation for the treatment of peripheral vascular and coronary artery disease. Efficacious application of this new therapy requires optimizing multiple factors including the therapeutic agent, dosing, frequency of administration, and delivery modality. Intramyocardial injection is evolving as the modality of choice for local myocardial treatment. In this study, we examined the distribution pattern and the efficiency of percutaneous intramyocardial injection for local protein delivery.

Methods: The device applied consisted of a helical needle infusion system that allowed stable myocardial engagement and delivery. 125Iodine-labeled albumin (0.4 ml total volume) was delivered in to the predetermined area of left ventricle in 8 swine (single delivery). Animals were sacrificed 1 hour later, and 1-2 gram sections of the entire cardiac tissue were examined for radioactivity. Continuous arterial and coronary sinus samples were collected to monitor the "wash-out" and re-circulation of the radioactivity after the delivery.

Results: Percutaneous intramyocardial delivery resulted in a high concentration of radiolabel at the treatment site: 16.4 ± 2.1% of delivered activity and 81.4 ± 2.6% of the total cardiac activity was concentrated at the site of delivery. Continuous coronary sinus and aortic blood sampling demonstrated that within 15 minutes following intramyocardial injection the majority of unbound protein is found within the coronary sinus. Despite direct intramyocardial delivery, significant amounts of radioactivity were found in non-trageted organs (24.3 ± 3.6% in liver, 11.5 ± 3.0% in kidneys, and 6.7 ± 1.9% in the lungs). However, the specific activity at the treatment site (radioactive counts per gram of tissue) was 115 ± 36, 226 ± 55, and 47 ± 10 fold higher compared to liver, lung, and kidney, respectively.

Conclusions: This study indicates that percutaneous intramyocardial injection is an efficient method for local myocardial treatment, and drug levels may be modulated by temporary occlusion of coronary sinus drainage during the delivery.

Journal of the American College of Cardiology, abstract 1157-28, Feb 2001.