A MODEL TO ASSESS INTERVENTIONS TO IMPROVE COLLATERAL BLOOD-FLOW - CONTINUOUS ADMINISTRATION OF AGENTS INTO THE LEFT CORONARY-ARTERY IN DOGS

Objective: The aim was to develop an experimental model in which angio genic growth factor(s) could be targeted locally to enhance myocardial collateral formation. A preparation was developed in which agents cou ld be infused selectively into the left main coronary artery on a chro nic basis to assess the potential of acidic fibroblast growth factor ( FGF) to improve collateral blood flow. Methods: Ameroid constrictors w ere placed on the left circumflex coronary artery of mixed hounds. Fiv e 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 con nected to an implantable infusion pump that provided continuous intrac oronary drug infusion for 4 weeks. Dogs were randomised to receive aci dic FGF with heparin (30 mug-h-1 and 30 IU.h-1, respectively, n=16) or heparin alone (30 IU.h-1, n=14). Regional myocardial blood flow was d etermined in the conscious state at the beginning and end of treatment . Results: There were no deaths or important surgical complications re lated to the establishment of the coronary artery infusions. During th e 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 hepar in; however, similar improvement was noted in dogs treated with hepari n alone. Ischaemic zone and normal zone vascular density was also equi valent in the two groups. Conclusions: This preparation makes possible the chronic intracoronary administration of agents which may promote myocardial angiogenesis, and allows assessment of collateral blood flo w before and after treatment. As given in this investigation, acidic F GF had no demonstrable effect on collateral blood flow; however, this model may facilitate the identification of agents that do enhance myoc ardial collateral formation.