Vascular growth factors as an adjunct to surgical revascularization

Strong theoretical concerns remain regarding the overall benefit of these therapies to prospective patients. The majority of the clinical manifestations of ischemic coronary artery disease are believed to result from the obstruction of medium-sized conduits that carry bulk flow to the heart, and the well documented benefit of revascularization therapy in these patients has come from re-establishment of that bulk flow through similarly large conduits. It remains to be seen whether an enhanced microvascular network that reduces vascular resistance can achieve similar increases in bulk blood flow. This question is particularly important when severe triple vessel disease exists, in which enhanced collateralization can only be achieved between equally poor sources of blood flow. Preclinical studies have indicated a relative increase in blood flow to ischemic tissues, but the functional significance of this effect has been less consistent, and its translation to a human clinical benefit is similarly uncertain. Furthermore, the long-term stability of this enhanced blood flow has not yet been established. The most realistic early applications of therapeutic neovascularization are therefore likely to reside in enhancement, rather than replacement, of conventional therapies. Neovascularization, which will almost always require weeks to months, is never likely to provide a means for treatment of acute ischemic syndromes. Adjunctive therapy for bypass and angioplasty may also prove an important arena for application, not just for areas of the heart that are inaccessible to bypass or angioplasty, but also to potentially enhance the benefit in tissue perfusion via further improvement of flow and microscopic collateralization. In this regard, higher patency rates, lower restenosis rates and even better symptomatic clinical outcomes may be achieved. Clinical scientists and vascular biologists are truly on the threshold of a new era in cooperation and in translation of basic science into clinical practice. The degree and speed with which this promise is realized will likely depend on the responsible and consistent approach that is adopted by investigators in the coming years.

Duke Scholars

Author Victor J. Dzau Medicine, Cardiology