Heart repair by stem cell treatment may involve life-threatening arrhythmias. Cardiac progenitor cells (CPCs) appear best suited for reconstituting lost myocardium without posing arrhythmic risks, being commissioned towards cardiac phenotype. In this study we tested the hypothesis that mobilization of CPCs through locally delivered Hepatocyte Growth Factor and Insulin-Like Growth Factor-1 to heal chronic myocardial infarction (MI), lowers the proneness to arrhythmias. We used 133 adult male Wistar rats either with one-month old MI and treated with growth factors (GFs, n = 60) or vehicle (V, n = 55), or sham operated (n = 18). In selected groups of animals, prior to and two weeks after GF/V delivery, we evaluated stress-induced ventricular arrhythmias by telemetry-ECG, cardiac mechanics by echocardiography, and ventricular excitability, conduction velocity and refractoriness by epicardial multiple-lead recording. Invasive hemodynamic measurements were performed before sacrifice and eventually the hearts were subjected to anatomical, morphometric, immunohistochemical, and molecular biology analyses. When compared with untreated MI, GFs decreased stress-induced arrhythmias and concurrently prolonged the effective refractory period (ERP) without affecting neither the duration of ventricular repolarization, as suggested by measurements of QTc interval and mRNA levels for K-channel α-subunits Kv4.2 and Kv4.3, nor the dispersion of refractoriness. Further, markers of cardiomyocyte reactive hypertrophy, including mRNA levels for K-channel α-subunit Kv1.4 and β-subunit KChIP2, interstitial fibrosis and negative structural remodeling were significantly reduced in peri-infarcted/remote ventricular myocardium. Finally, analyses of BrdU incorporation and distribution of connexin43 and N-cadherin indicated that cytokines generated new vessels and electromechanically-connected myocytes and abolished the correlation of infarct size with deterioration of mechanical function. In conclusion, local injection of GFs ameliorates electromechanical competence in chronic MI. Reduced arrhythmogenesis is attributable to prolongation of ERP resulting from improved intercellular coupling via increased expression of connexin43, and attenuation of unfavorable remodeling.
SummaryBackground: The Senning operation for transposition of the great arteries (TGA) was first introduced by Senning in 1959 and was revived by Quaegebeur et al. in the late 1970s, thus becoming the intervention of choice for the correction of TGA in many centers.Hypothesis: The purpose of this study was to evaluate the long-term follow-up of a group of patients undergoing surgery with the Senning procedure for TGA.Methods: From November 1978 to November 1987, 73 consecutive patients underwent the Senning operation. The 70 survivors had an average follow-up of 19 years (16-25 years).Results: (1) Cardiac rhythm: with time there was a progressive decrease in stable sinus rhythm (60% after 20 years) and a progressive increase of supraventricular tachyarrhythmias requiring therapy (10% after 20 years). (2) Right ventricular function: 20% of the patients had reduced ejection fraction. (3) Late mortality: in the last 12 years of follow-up years there were two sudden deaths (2.8%). (4) Functional status: 80% of patients were in NYHA class I, 17% in class II, and 3% in class III.Conclusions: Our results confirm that the patients who undergo the Senning procedure have a progressive loss of sinus rhythm, an increase in active arrhythmias, and other important adverse outcomes such as late sudden death and a decrease in right ventricular function; however, most patients (93% in our series) are alive and in good functional status.
Isolation of the left subclavian artery has been reported in cases of tetralogy of Fallot with a right aortic arch. As the isolated left subclavian artery is supplied by the left vertebral artery (in which the blood flow direction is inverted), this anomaly is usually responsible for a congenital subclavian steal phenomenon. In our case the isolated left subclavian artery was connected by a patent ductus arteriosus to the main pulmonary artery. Therefore the left vertebral artery did not supply the distal left subclavian artery but supplied the main pulmonary artery (congenital pulmonary artery steal).
Successful transcatheter device closure of secundum atrial septal defect has achieved worldwide acceptance with the clinical use of the Amplatz atrial septal occluder. However, device closure of multiple fenestrated secundum atrial septal defects remains a challenge for the interventionist and in some cases may be only effectively closed surgically. This case report of multiple fenestrated atrial septal defects represents a further expansion of technologic efforts to improve the results and simplify the mechanism of device closure of fenestrated defects. When device closure with more than one device seems impractical or disadvantageous, consolidation of multiple defects in a fenestrated fossa ovalis by simple balloon atrial septostomy as demonstrated by this case report provides an easy mechanism to allow implantation of a single large device which will effectively close all of the defects. This approach is similar to the surgical approach for resection of the fenestrated membrane with secondary patch closure of the enlarged defect. Excellent and complete closure of a fenestrated secundum atrial septal defect is illustrated in this case report.
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