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Background: The purpose of this study was to test the hypothesis that there is a relation between collateral flow and intracoronary concentrations of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) and that the combined concentrations of both growth factors and the extent of coronary artery disease (CAD) play a role as covariables in such an association., Methods and Results: In 76 patients undergoing balloon angioplasty, a collateral flow index (CFI, no units) was determined with sensor-tipped guidewires. Simultaneously, serum concentrations of bFGF and VEGF, obtained at the aortic root from the ostium of the collateralized coronary artery (n = 76) and from the distal position of the occluded coronary artery (n = 34), were determined. There was a direct correlation between CFI and distal VEGF (r = 0.33, P = 0.05) but not bFGF concentrations. Focusing on the proximal sampling site, there was a direct correlation between CFI and both bFGF (r = 0.29, P = 0.01) and VEGF concentrations (r = 0.44, P < 0.0001). The sum of the concentrations of both growth factors was directly associated with CFI irrespective of the proximal (r = 0.51, P < 0.0001) or distal sampling site (r = 0.34, P = 0.048). There was a trend toward higher proximal VEGF concentrations in patients with higher numbers of coronary stenotic lesions (r = 0.25, P = 0.03)., Conclusions: In patients with CAD, there is an association between a directly measured index of collateral flow and intracoronary concentrations of bFGF and VEGF. This direct relation is dependent on the site of blood sampling within the coronary artery tree. The association is closest when the combined bFGF and VEGF concentrations are taken into account. In the case of VEGF, it is influenced by the degree of coronary atherosclerosis.

Background: Endothelin is a potent endothelium-derived vasoconstrictor peptide with proliferative properties. Elevated levels of the peptide occur in coronary artery disease; however, its pathophysiological role as a regulator of coronary tone and structure is uncertain. Endothelin-receptor antagonists are specific tools to clarify this issue and might be useful in the treatment of coronary artery disease., Methods and Results: In a double-blind, placebo-controlled randomized study, we investigated the effects of the ETA/ETB endothelin-receptor antagonist bosentan or placebo on systemic and coronary hemodynamics in 28 patients with angiographically documented stable coronary artery disease by quantitative coronary angiography and an intracoronary Doppler guidewire. Bosentan 200 mg IV decreased systolic blood pressure (P<0. 05), whereas heart rate increased slightly (P<0.05). Coronary diameter increased, particularly in vessels with no or mild angiographic changes (P<0.01). Glycerol trinitrate did not further dilate these segments, whereas coronary diameter increased significantly after nitrate in the placebo group. The increase in coronary diameter after bosentan correlated inversely with plasma LDL-cholesterol levels (P<0.01) in both stenotic and angiographically normal coronary segments. Coronary flow velocity did not change. Bosentan was well tolerated., Conclusions: Endogenous endothelin exerts a vasoconstrictor tone in epicardial coronary arteries of patients with coronary artery disease, as evidenced by the vasodilation exerted by the combined ETA/ETB endothelin-receptor antagonist bosentan under acute conditions. Bosentan can safely be given to these patients. Hence, further long-term studies are necessary to determine the therapeutic potential of endothelin-receptor antagonists in patients with coronary artery disease.

Background: Coronary steal is defined as a fall in blood flow toward a certain vascular region in favor of another area during arteriolar vasodilatation, ie, a coronary flow velocity reserve (CFVR) <1. The purpose of this study was to determine the frequency of steal in patients with a wide range of collateral supply to a vascular area of interest and to assess whether steal is associated with the amount of collateral flow., Methods and Results: One hundred patients 57+/-9 years old with a coronary artery stenosis to be dilated were examined with intracoronary (IC) Doppler guidewires. IC adenosine-induced CFVR<1 obtained distal to the stenosis was defined as steal. An index for collateral flow was determined by positioning the Doppler guidewire in the collateral-dependent vessel distal to the stenosis and measuring the flow velocity time integral during (Vi(occl), cm) and after (Vi(ø-occl)) balloon occlusion. Vi(occl)/Vi(ø-occl) was determined without and with intravenous adenosine (140 microg x kg(-1) x min(-1)). Coronary steal occurred in 10 of 100 patients. Patients with steal showed superior collaterals compared with those without steal: Vi(occl)/Vi(ø-occl)=0.65+/-0.24 in patients with steal versus 0.29+/-0.18 in those without steal (P=.0001). In all patients with steal, there was a reduction in collateral flow during intravenous adenosine-induced hyperemia, whereas in the majority (70%) of patients without steal, collateral flow increased or remained unchanged during hyperemia., Conclusions: Coronary steal assessed by intracoronary Doppler flow velocity measurements occurs in 10% of patients with a wide range of coronary collaterals to the vascular area from which blood flow is redistributed. There is a direct association between the presence of steal away from and the amount of collateral flow toward the region under investigation. Collateral flow to the vascular region studied decreases during adenosine-induced hyperemia, which indicates a mechanism of steal via the extensive collaterals.