Less-invasive method for microsphere delivery to coronary circulation and evaluation of myocardial ischemic change in...

We developed a less-invasive method for semi-selective administration of drugs into coronary arteries in small animals. With this method, we created microvascular myocardial ischemia in rabbits by microsphere injection. A 4F catheter was inserted into the left ventricle via the right common carotid artery and a balloon catheter into the descending thoracic aorta. Microspheres were administered into the left ventricle with temporary occlusion of the descending aorta and carotid arteries. In these conditions, regional blood flow in the heart was 10.8-times as much as in the kidney. Seventeen days after microsphere injection, the contractile function of the heart muscle deteriorated and the left ventricular endodiastolic pressure was increased. Patchy NADH-fluorescence was observed all over the left ventricular myocardium. Myocardial lactate concentration was higher than the normal standard animals. Histological analysis revealed that microscopic patchy necrosis was noted only in the myocardium but not in other organs. Semi-selective delivery of recombinant adenovirus expressing lacZ using the same method induced a gene expression in the heart. Thus, a unique model for microvascular myocardial ischemia was created by semi-selective delivery of microspheres into the coronary artery without special technique or equipment. The present model is also applicable to semi-selective gene transfer to the heart.