Tetralogy of Fallot: aorto-pulmonary collaterals and pulmonary arteries have distinctly different transcriptomes.

BACKGROUND: Tetralogy of Fallot patients with pulmonary atresia (TOF/PA) present a pulmonary blood supply directly from aortic collateral arteries. Major aorto-pulmonary collateral arteries (MAPCAs) present substantial clinical and surgical management challenges. Surgical operations to reestablish and promote further development of a pulmonary arterial connection preferentially utilize MAPCAs for reconstruction of central pulmonary arteries. However, the propensity of some MAPCAs to develop stenosis rather than growth may impair the response to reconstructions. METHODS: Probe sets prepared from MAPCAs, PA, and aorta mRNA were used to interrogate human genome microarrays. We compared expression differences between pairs of the three vessels to determine whether MAPCAs display distinct expression patterns. RESULTS: Functional clustering analysis identified differences in gene expression, which were further analyzed by gene ontology classification. A subset of highly regulated genes was validated using quantitative PCR. Expression differences among vessel types were observed for multiple gene classes. Of note, we observed that MAPCAs differentially express several genes at much higher levels than either PA or aorta. CONCLUSION: MAPCAs differ from PA or aorta by significantly altered levels in gene expression, suggesting a transcriptional basis for their physiology that will guide a further understanding of the pathobiology of MAPCAs and TOF.

Subaortic membrane and aorto-septal angle: an echocardiographic assessment and surgical outcome.

BACKGROUND: Development of a subaortic membrane is not fully understood. Recurrence after surgical removal continues to be high. We sought to assess the differences in aorto-septal angles (AoSA) to possibly explain alterations within the left ventricular outflow tract, hence in subaortic membrane formation. METHODS: A total of 113 patients who underwent subaortic membrane resection were matched by age and sex with 113 controls. The subaortic membrane resection group included isolated subaortic membranes (n = 34, group I), associated with ventricular septal defect (n = 29, group II), or patent ductus arteriosus (n = 50, group III). RESULTS: Mean (± standard deviation) AoSA (in degrees) were not different between subaortic membrane groups I, II, and III but were steeper than their control groups (126.2 ± 9.2 vs 138.6 ± 7.0, 129.2 ± 9.9 vs 137.7 ± 10.0, and 126.2 ± 8.1 vs 135 ± 8.5, respectively; all Ps < .05). Additionally, group II had lower preoperative gradients (28.8 ± 20.7 mm Hg) compared to groups I and III (67.0 ± 32.9 and 66.2 ± 33.1 mm Hg, respectively, P < .001). Follow-up ranged from 3 to 132 months. In 22 (32%) patients, a subaortic membrane recurred. Early postoperative residual gradients and development of aortic regurgutation were associated with the need for reoperation (P < .05). CONCLUSIONS: These findings suggest a contributing role of the AoSA in the development of subaortic membrane. Further rheological experiments are warranted. Whether the steeper the angle the higher the risk of recurrence may be revealed by longer follow-up periods.

Reconstruction of pulmonary artery in a newborn using a porcine small intestinal submucosal patch.

In this case report, we evaluated cellular structure and the growth potential of a porcine small intestinal submucosal patch used for pulmonary artery augmentation in a 20-day-old newborn with pulmonary atresia. The patch was resected 2 months postoperatively due to apparent abnormal wall thickening and evaluated by histologic and immunohistologic staining.

Are purified or expanded cord blood-derived CD133+ cells better at improving cardiac function?

Endothelial progenitor cells (EPCs), which express the CD133 marker, can differentiate into mature endothelial cells (ECs) and create new blood vessels. Normal angiogenesis is unable to repair the injured tissues that result from myocardial infarction (MI). Patients who have high cardiovascular risks have fewer EPCs and their EPCs exhibit greater in vitro senescence. Human umbilical cord blood (HUCB)-derived EPCs could be an alternative to rescue impaired stem cell function in the sick and elderly. The aim of this study was to purify HUCB-derived CD133(+) cells, expand them in vitro and evaluate the efficacy of the purified and expanded cells in treating MI in rats. CD133(+) cells were selected for using CD133-coupled magnetic microbeads. Purified cells stained positive for EPC markers. The cells were expanded and differentiated in media supplemented with fetal calf serum and basic fibroblast growth factor, insulin-like growth factor-I and vascular endothelial growth factor (VEGF). Differentiation was confirmed by lack of staining for EPC markers. These expanded cells exhibited increased expression of mature EC markers and formed tubule-like structures in vitro. Only the expanded cells expressed VEGF mRNA. Cells were expanded up to 70-fold during 60 days of culture, and they retained their functional activity. Finally, we evaluated the therapeutic potential of purified and expanded CD133(+) cells in treating MI by intramyocardially injecting them into a rat model of MI. Rats were divided into three groups: A (purified CD133(+) cells-injected); B (expanded CD133(+) cells-injected) and C (saline buffer-injected). We observed a significant improvement in left ventricular ejection fraction for groups A and B. In summary, CD133(+) cells can be purified from HUCB, expanded in vitro without loosing their biological activity, and both purified and expanded cells show promising results for use in cellular cardiomyoplasty. However, further pre-clinical testing should be performed to determine whether expanded CD133(+) cells have any clinical advantages over purified CD133(+) cells.