Internal thoracic artery grafts for the entire heart at a mean of 12 years.

BACKGROUND: There is consensus today that the long-term results of bypassing the left anterior descending artery with an internal thoracic artery (ITA) graft are superior to those of a saphenous vein graft. Our hypothesis for this study was that three-vessel revascularization with only ITA grafts would also give excellent results. METHODS: Using our previously described techniques to enhance the length of ITA grafts by skeletonization and high mediastinal mobilization, we were able to perform tension-free, three-vessel revascularization using only ITA grafts in 125 (83%) of a consecutive series of 150 patients with three-vessel occlusive coronary disease. We followed 100% of these 125 exclusive ITA graft patients (average of 3.9 anastomoses per patient) to their time of death (59; 47.2%) or current living status (66; 52.8%). RESULTS: Combined intraoperative graft flows averaged 225 mL/min. Of the 125 patients in this study (average age, 63.5 years), 121 (96.8%) lived beyond 40 days. Of these 121 patients, 55 (45%) died at a mean of 7 years postoperatively and 66 (55%) are still living at a mean of 12.1 years. Of these 121 patients, 112 (93%) had angina at baseline. Of these 112, 92 (85%) were angina free at a mean of 9.1 years postoperatively. Freedom from infarction was 100% at 5 years and 97% at 10 years. Freedom from reintervention was 90% at a mean of 9.8 years. CONCLUSIONS: Use of ITA grafts for three-vessel coronary revascularization provides excellent results and is both practical and appropriate for many patients.

Novel vascular endothelial growth factor binding domains of fibronectin enhance vascular endothelial growth factor biological activity.

Interactions between integrins and growth factor receptors play a critical role in the development and healing of the vasculature. This study mapped two binding domains on fibronectin (FN) that modulate the activity of the angiogenic factor, vascular endothelial growth factor (VEGF). Using solid-phase assays and surface plasmon resonance analysis, we identified two novel VEGF binding domains within the N- and C-terminus of the FN molecule. Native FN bound to VEGF enhanced endothelial cell migration and mitogen-activated protein (MAP) kinase activity, but FN that is devoid of the VEGF binding domains failed to do so. Coprecipitation studies confirmed a direct physical association between VEGF receptor-2 (Flk-1) and the FN integrin, alpha5beta1, which required intact FN because FN fragments lacking the VEGF binding domains failed to support receptor association. Thrombin-activated platelets released intact VEGF/FN complexes, which stimulated endothelial cell migration and could be inhibited by soluble high affinity VEGF receptor 1 and antibodies to alpha5beta1 integrin. This study demonstrates that FN is potentially a physiological cofactor for VEGF and provides insights into mechanisms by which growth factor receptors and integrins cooperate to influence cellular behavior.