A model to assess interventions to improve collateral blood flow: continuous administration of agents into the left coronary artery in dogs

Abstract

The aim was to develop an experimental model in which angiogenic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents could be infused selectively into the left main coronary artery on a chronic basis to assess the potential of acidic fibroblast growth factor (FGF) to improve collateral blood flow. Ameroid constrictors were placed on the left circumflex coronary artery of mixed hounds. Five weeks after ameroid placement, the artery was ligated and transected at the point of ameroid occlusion; a catheter was inserted and passed retrogradely into the left main coronary artery. The catheter was connected to an implantable infusion pump that provided continuous intracoronary drug infusion for 4 weeks. Dogs were randomised to receive acidic FGF with heparin (30 micrograms.h-1 and 30 IU.h-1, respectively, n = 16) or heparin alone (30 IU.h-1, n = 14). Regional myocardial blood flow was determined in the conscious state at the beginning and end of treatment. There were no deaths or important surgical complications related to the establishment of the coronary artery infusions. During the treatment interval (5-9 weeks after ameroid placement) the ratio of maximum ischaemic zone/normal zone blood flow increased from 0.39(SD 0.10) to 0.50(0.11) (p < 0.01) in dogs treated with acidic FGF plus heparin; however, similar improvement was noted in dogs treated with heparin alone. Ischaemic zone and normal zone vascular density was also equivalent in the two groups. This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flow before and after treatment. As given in this investigation, acidic FGF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myocardial collateral formation.