Modulation of myocardial perfusion and vascular reactivity by pericardial basic fibroblast growth factor: Insight into ischemia-induced reduction in endothelium-dependent vasodilatation

Objectives: The present study was designed to study the effects of a single intrapericardial injection of basic fibroblast growth factor on myocardial vascular resistance and endothelium-dependent microvascular dilatation in a porcine model of chronic myocardial ischemia and to investigate the mechanism of ischemia-induced impairment of endothelium-dependent vasodilatation, Methods: Yorkshire pigs underwent ameroid constrictor placement on the left circumflex coronary artery. At 3 weeks, animals were randomized to a single intrapericardial injection of saline solution (n = 10), 30 mu g basic fibroblast growth factor (n = 10), or 2 mg basic fibroblast growth factor (n = 10), Myocardial vascular resistance in the normal (left anterior descending) and ischemic collateral-dependent (left circumflex artery) territories (using colored microspheres) and microvascular reactivity to adenosine diphosphate and sodium nitroprusside were measured before treatment and 4 weeks after treatment. The expression of inducible and endothelial nitric oxide synthase was determined in normal and ischemic myocardium by means of reverse transcriptase-polymerase chain reaction and Western analysis, and the effect of nitric oxide on endothelium-dependent vasodilatation was determined. Results: Compared with results in the control group, treatment with basic fibroblast growth factor resulted in significant improvement in left circumflex artery resistance and endothelium-dependent vasodilatation, reflecting increased collaterals. Myocardial ischemia was associated with increased expression of inducible nitric oxide synthase with no change in endothelial nitric oxide synthase, However, the nitric oxide donor sodium nitroprusside did not affect endothelium-dependent vasodilatation to adenosine diphosphate. Conclusions: A single intrapericardial bolus of basic fibroblast growth factor may be a useful therapeutic strategy for the treatment of myocardial ischemia in patients with coronary artery disease. Although chronic myocardial ischemia is associated with increased expression of inducible nitric oxide synthase, it does not appear to be the cause of altered endothelial function.