Ann Thorac Surg 2000;70:2118
© 2000 The Society of Thoracic Surgeons
Invited commentary
Todd Rosengart, MDa
a Division of Cardiothoracic Surgery, Evanston Northwestern Healthcare, Northwestern University Medical School, 2650 Ridge Ave, Evanston, IL 60201, USA
e-mail: trosengart{at}enh.org
A growing number of experimental studies continue to strengthen the evidence base suggesting the feasibility of administering angiogenic growth factor as a means of "biologically" revascularizing ischemic tissues. This strategy, termed therapeutic angiogenesis, has now been shown to induce the neovascularization of a wide variety of tissues. A number of studies, including this report by Sato and associates, suggest that this neovascularization response to growth factor delivery is sufficiently robust to significantly enhance myocardial function, as well as perfusion. In fact, similarly effective results with a wide variety of angiogenic mediators have thus far made it difficult to discern a relative efficacy advantage of one of these mediators as compared with any others. As noted by Sato and associates, the most significant difference in reported results of angiogenic regimens appears to be in regard to method of delivery. For the treatment of cardiac disease, localized intracoronary or intramyocardial therapy appears to be uniformly superior to systemic therapy. While intracoronary therapy yielded significant results in the present study, other reports suggest potentially advantageous pharmacokinetics with intromyocardial as opposed to intracoronary delivery. In this regard, one unanswered question is whether the potential ease of catheter-based intracoronary delivery outweighs the potentially superior efficacy of intramyocardial delivery of angiogenic growth factors (whether delivered "surgically" via an epicardial route or percutaneously via an endocardial route).
An even more daunting challenge to the promise of angiogenic therapy is presented by the apparent discrepancy between the robust responses noted in experimental angiogenic models in "normal" tissues such as in the present study, and the somewhat less profound responses reported from initial clinical trials. It is unknown whether this discrepancy represents a "false negative" due to the limitations of clinical diagnostic methodologies, or whether the challenge of inducing angiogenesis in a potentially unfavorable millieu (elderly, diabetic, hypercholesterolemic, atherosclerotic subjects) is a true barrier to clinical success. More stringent experimental studies and clinical trials, possibly involving more sophisticated angiogenic "cocktails" or sequenced growth factor administration regimens, in addition to the adaptation of refined diagnostic modalities, will likely be needed before this question can be answered. While the initial data regarding angiogenic therapies remain encouraging, much work remains ahead.
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Ann. Thorac. Surg. 2000 70: 2113-2118.
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