Evaluation of the percutaneous intramyocardial injection for local myocardial treatment.
Therapeutic angiogenesis requires the induction 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. In this study, a helical needle drug infusion catheter was applied for optimal application of percutaneous intramyocardial delivery (PIMD). (125)Iodine-labeled albumin was injected by PIMD into the left ventricle myocardium in eight swine. After 1 hr, PIMD resulted in a high concentration of radiolabel at the treatment site; 16.4% +/- 2.1% of delivered and 81.4% +/- 2.6% of the total cardiac activity was concentrated at the site of delivery. The depth of needle penetration correlated with the myocardial retention of delivered protein. The myocardial retention of radiolabel in animals with shallow injections was 10.1% +/- 0.8%, compared to 18.9% +/- 3.3% retention after deep injections. The specific activity at the treatment site (radioactive counts per gram of tissue) was 115 +/- 36, 226 +/- 55, and 47 +/- 10 times higher compared to liver, lung, and kidney, respectively. Continuous coronary sinus and aortic blood sampling indicates that within 15 min following intramyocardial injection, a significant amount of nonretained protein is found within the coronary sinus. This study defines some of the parameters that can affect optimal application of PIMD and demonstrates that PIMD is a safe and efficient method for local drug delivery.
Rezaee
M
M
Division of Cardiovascular Medicine, Stanford University Hospital, Stanford, California, USA. mrezaee@leland.stanford.edu
Yeung
A C
AC
Altman
P
P
Lubbe
D
D
Takeshi
S
S
Schwartz
R S
RS
Stertzer
S
S
Altman
J D
JD
D000818:Animals; D009202:Cardiomyopathies / Q000628:therapy*; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000008:administration & dosage; D005471:Fluoroscopy; D007267:Injections / Q000379:methods*; D007457:Iodine Radioisotopes; D008863:Microspheres; D009206:Myocardium / Q000737:chemistry
D005456:Fluorescent Dyes; D007457:Iodine Radioisotopes