Background-We investigated whether catheter-based, intramyocardial transplantation of autologous endothelial progenitor cells can enhance neovascularization in myocardial ischemia. Methods and Results-Myocardial ischemia was induced by placement of an ameroid constrictor around swine left circumflex artery. Four weeks after constrictor placement, CD31ϩ mononuclear cells (MNCs) were freshly isolated from the peripheral blood of each animal. After overnight incubation of CD31ϩ MNCs in noncoated plates, nonadhesive cells (NA/CD31ϩ MNCs) were harvested as the endothelial progenitor cell-enriched fraction. Nonadhesive CD31Ϫ cells (NA/CD31Ϫ MNCs) were also prepared. Autologous transplantation of 10 7 NA/CD31ϩ MNCs, 10

The surgical treatment of aortopulmonary window has a low risk, even if associated with major cardiac anomalies. Prompt operative treatment achieves excellent long-term results.

Both VEGF protein and VEGF DNA in combination with an adenoviral vector have been shown to enhance collateral formation in a porcine model of chronic myocardial ischemia. We sought to determine whether direct intramyocardial injection of naked DNA encoding for VEGF could similarly improve myocardial perfusion. Initially, 23 nonischemic pigs received either 200 microg of plasmid DNA encoding beta-galactosidase (pCMVbeta, n = 11) or 500 microg of phVEGF165 (n = 12) into four separate sites in the myocardium via a small anterolateral thoracotomy incision in the fourth intercostal space. Two additional groups of pigs received an intramyocardial injection of either phVEGF165 (n = 6) or pCMVbeta (n = 7) 3 to 4 weeks after implantation of an ameroid constrictor around the left circumflex coronary artery. The injections caused no change in heart rate or blood pressure, and no ventricular arrhythmias or histologic evidence of inflammation. VEGF protein was detected by Western blot in VEGF-treated animals, with the strongest bands closest to the injection site. Plasma VEGF concentration (ELISA) increased from 3+/-2 to 27+/-13 pg/ml (p = 0.035) by day 4 after treatment. No increase in VEGF protein was noted in pCMVbeta-treated animals whereas these did stain positive for beta-Gal. Resting myocardial blood flow (colored microspheres) was significantly reduced in the ischemic versus nonischemic territory in control animals (1.07+/-0.05 versus 1.32+/-0.05; p < 0.05) but not VEGF-treated pigs (1.32+/-0.24 versus 1.13+/-0.12; p = NS). Maximal vasodilatation with adenosine significantly increased flow to the ischemic region in VEGF-treated pigs (2.16+/-0.57 versus 1.32+/-0.24; p < 0.05) but not controls (1.31+/-0.05 versus 1.17+/-0.06;p = NS). Collateral filling of the occluded circumflex artery improved in five of six VEGF-treated pigs (mean change in Rentrop score, +1.5). We conclude that direct intramyocardial transfection phVEGF165 is safe and capable of producing sufficient VEGF protein to enhance collateral formation and myocardial perfusion. This approach may offer an alternative therapy for patients with intractable myocardial ischemia not amenable to PTCA or CABG.

Coronary artery fistula is a very rare congenital malformation with an abnormal coronary-cameral communication that may involve any chamber and any or all coronary artery branches. We present our experience with 11 consecutive patients (mean age 16.6 years, ranging from 4 to 64 years); 9 of them were treated surgically, spontaneous closure of the fistula was observed in 1 patient and 1 patient is still under observation. Nine patients were under 17 years of age at the time of operation whereas only 2 patients were older (56 and 64 years). Fistulas originated from the right coronary artery in 4 patients and drained either into the right (n = 3) or into the left system (n = 1). In 8 patients, the origin of the coronary artery from the aorta was normal and the fistulous communication developed with the right cardiac structures only. In 2 patients, both coronary arteries were involved in the pathological drainage and 2 patients were demonstrated to have multiple drainage from the left coronary artery. Additional congenital cardiac malformations were found in 2 patients: severe tricuspid valve regurgitation in 1 and ventricular septal defect in another patient. Surgical closure of the fistula was successful in all operated patients (in 1 case treatment was possible without cardiopulmonary bypass). Simple ligation of the fistula was performed in 1 patient, intracardiac closure of the fistula was combined with different reconstructive procedures in the other patients. No hospital mortality nor severe complications occurred in this small group of patients. The mean follow-up interval was 39.4 months and all patients were in NYHA functional class I, except 1 with moderate tricuspid and mitral valve regurgitation. In the presence of symptoms of congestive heart failure, significant left-to-right shunt and arrhythmias, elective closure of coronary fistula is generally accepted, whereas the indication is more controversial in asymptomatic patients. Considering the low perioperative morbidity, we recommend surgical closure of coronary fistulas with significant shunt and/or increased coronary artery diameter.

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