Local intracoronary heparin delivery with a microporous balloon catheter

Arterial thrombosis plays a major role in the pathogenesis of acute coronary syndromes such as unstable angina and acute myocardial infarction. Heparin is efficacious in treating both disorders; however, systemically administered heparin is associated with bleeding complications. Local intracoronary delivery of heparin may be a safer, more effective method of administration. This study was performed to determine the fate of heparin infused with a specially designed catheter for local intracoronary delivery. To quantitate heparin delivery, tritiated-labeled heparin was dissolved in a solution of unlabeled heparin (1,000 U/ml). A microporous balloon catheter was placed in the left anterior descending (LAD) and left circumflex arteries of anesthetized pigs (n = 15), and 1 ml of the heparin solution was infused. The animals were euthanized within 1 hour, and the treated arteries and controls were harvested, processed, and the tritiated activity was measured. To assess the distribution of the heparin in the arterial wall, 1 ml of fluorescein-isothiocyanate (FITC)-labeled heparin was locally delivered into the walls of the LAD and left circumflex arteries with the microporous balloon catheter. To visualize the dynamic fluid transfer of the device, a microporous balloon catheter was inflated in the LAD, and 1 ml of diluted contrast medium was infused under cinefluoroscopy. The arteries treated with tritiated-labeled heparin contained 0.6% ± 0.2% of the infused heparin dose. Control arteries contained 0.01% of the administered heparin. Animals that were infused with FITC-labeled heparin displayed fluorescence throughout all layers of the artery, especially in the adventitia. In animals that were injected with 1 ml of diluted contrast medium through the microporous balloon, a relatively large amount of the infusate appeared in the arterial lumen proximal to the balloon. In conclusion, these results suggest that heparin can be delivered to coronary arteries with a microporous balloon catheter. However, <1% of the infused dose can be found in the artery 1 hour after delivery. Infused haperin is distributed throughout the arterial wall, but most of the infused solution appears in the arterial lumen proximal to the inflated balloon and is probably washed downstream after balloon deflation.