Milestones in pediatric cardiology: making possible the impossible.

Pediatric Cardiology as a discipline has been proposed to have been born on August 26, 1938, when Robert Gross at the age of 33 years, successfully ligated a patent ductus arteriosus of a 7 years girl at the Children's Hospital in Boston. In November 1944, Helen Taussig convinced Alfred Blalock to anastomose the left subclavian artery to the left pulmonary artery after Robert Gross had declined to cooperate with her. About the 1950s, at the University of Minneapolis, Clarence Walton Lillehei worked on a controlled "crossed circulation" in which the cardiopulmonary bypass machine was another human, generally one of the patient's parents. In 1966 Williams Rashkind introduced ballon septostomy as a palliative approach to complete transposition of the Great Arteries, followed later by Jean Kan's balloon valvuloplasty to open the pulmonary valve. During the 1960s Giancarlo Rastelli developed a new classification of the Atrio Ventricular Canal defect which allowed to have a strikingly better surgical results. Today, even the hypoplastic left heart syndrome (HLHS), at one time a fatal condition, is operable. The completion of the Human Genome Project has been an enormous help in the understanding the genetic causes of cardiac anomalies. However, there are very few approved application for stem cells, and stem cells will not likely replace organ transplantation any time soon. Recently, the protein survivin has been described as a novel player in cardioprotection against myocardial ischemia/reperfusion injury. The science needs to be made with love to warrant the humanity of Research.

Transposition of the great arteries.

PURPOSE OF REVIEW: Transposition of the great arteries (TGA) is a complex congenital heart defect usually defined within the group of conotruncal defects. Some astonishing similarities between the spiral pattern of great arteries and the spiral pattern of snail shells and a possible common genetic mechanism of normal and abnormal anatomical aspects of the heart and shells are examined. RECENT FINDINGS: The pulmonary vascular resistances in TGA and ventricular septal defect (VSD) need to be assessed before surgery, as they are the key factors for the success of the surgical procedure. A noninvasive method has been proposed to assess this key factor. A first series of the pregnancy outcomes in young women after arterial switch operation (ASO) is promising and encouraging for even better results. The systemic failing right ventricle (RV) is treated empirically using the same drugs and devices as for the failing left ventricle. The rationale for the treatment of ventricular failure, similar or different for predominantly right or left ventricle, is debated. The results of Rastelli operation are compared with those of the other surgical procedures for the treatment of TGA, VSD and pulmonary stenosis, namely reparation a l'ètage ventriculaire and Nikaidoh interventions. SUMMARY: This review outlines some new aspects of the embryologic cardiac development and reveals astonishing similarities between heart and shells. A new diagnostic noninvasive method for measuring pulmonary vascular resistances, the pregnancy outcome of a first series of women operated by ASO, and the pharmacological and cardiac devices used in the failing systemic RV are presented. Finally, the review comments on the Rastelli operation as the 'gold standard' for TGA, VSD, and pulmonary stenosis.

Growth factor-induced mobilization of cardiac progenitor cells reduces the risk of arrhythmias, in a rat model of chronic myocardial infarction.

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 ß-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.