Physiologically assessed collateral flow and intracoronary growth factor concentrations in patients with 1- to 3-vessel coronary artery disease.

Intracoronary Growth Factor Concentrations in Patients With 1to 3-Vessel Coronary Artery Disease To the Editor: We enjoyed reading the article by Fleisch et al1 but would like to point out a number of potential factors that detract from the data reported. In particular, we are concerned about the measurement of growth factors and collateral flow index (CFI). As the authors acknowledge, both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are heparin-binding peptides and, thus, their levels are significantly altered in the presence of heparin. The administration of “nearly identical doses of heparin” does not normalize for heparin’s effects, because plasma heparin levels will vary according to the patient’s body mass, plasma volume, and age.2 We have found that after a standard 10 000-unit heparin bolus, both arterial and venous plasma VEGF levels can be undetectable when using using the same enzyme-linked immunoabsorption assay (ELISA) as Fleisch et al,1 even when there is a 50-fold difference in baseline sample concentrations before heparin administration. This probably explains why one-fifth of the study patients had undetectable VEGF levels. Conversely, arterial bFGF levels are elevated after heparin administration. There is a 3to 5-fold increase at 30 minutes after heparinization for cardiopulmonary bypass, probably because heparin displaces bFGF from the subendothelial extracellular matrix and luminal surface of blood vessels.3 Similarly, we have found up to a 10-fold increase in arterial bFGF 5 minutes after the administration of 10 000 units of intravenous heparin before angioplasty. The effects of heparin on VEGF and the variable effect of bFGF displacement from the arterial luminal surface are fundamental confounding factors that were not adequately accounted for in this article. The accurate measurement of CFI is heavily dependant on a correct evaluation of right atrial pressure at the time of balloon inflation. In our experience, if the mean right atrial pressure is assumed to be 5 mm Hg, CFI is overestimated by an average of 30%. This may explain why Fleisch et al1 used a CFI of 0.3 as the cut off point for sufficient collateral vessel development to protect against ischemia, as opposed to the theoretical and experimentally validated ratio of 0.25.4 Therefore, significant differences exist in the true CFI of the patients studied, which could alter their assignment to the high and low CFI groups. In summary, we question the reliability of the measurements of growth factors and collateral flow and believe that their relationship may be less certain than the authors conclude.