Apoptosis and epicardial contributions act as complementary factors in remodeling of the atrioventricular canal myocardium and atrioventricular conduction patterns in the embryonic chick heart.

BACKGROUND: During heart development, it has been hypothesized that apoptosis of atrioventricular canal myocardium and replacement by fibrous tissue derived from the epicardium are imperative to develop a mature atrioventricular conduction. To test this, apoptosis was blocked using an established caspase inhibitor and epicardial growth was delayed using the experimental epicardial inhibition model, both in chick embryonic hearts. RESULTS: Chicken embryonic hearts were either treated with the peptide caspase inhibitor zVAD-fmk by intrapericardial injection in ovo (ED4) or underwent epicardial inhibition (ED2.5). Spontaneously beating embryonic hearts isolated (ED7-ED8) were then stained with voltage-sensitive dye Di-4-ANEPPS and imaged at 0.5-1 kHz. Apoptotic cells were quantified (ED5-ED7) by whole-mount LysoTracker Red and anti-active caspase 3 staining. zVAD-treated hearts showed a significantly increased proportion of immature (base to apex) activation patterns at ED8, including ventricular activation originating from the right atrioventricular junction, a pattern never observed in control hearts. zVAD-treated hearts showed decreased numbers of apoptotic cells in the atrioventricular canal myocardium at ED7. Hearts with delayed epicardial outgrowth showed also increased immature activation patterns at ED7.5 and ED8.5. However, the ventricular activation always originated from the left atrioventricular junction. Histological examination showed no changes in apoptosis rates, but a diminished presence of atrioventricular sulcus tissue compared with controls. CONCLUSIONS: Apoptosis in the atrioventricular canal myocardium and controlled replacement of this myocardium by epicardially derived HCN4-/Trop1- sulcus tissue are essential determinants of mature ventricular activation pattern. Disruption can lead to persistence of accessory atrioventricular connections, forming a morphological substrate for ventricular pre-excitation. Developmental Dynamics 247:1033-1042, 2018. © 2018 Wiley Periodicals, Inc.

[Ventricular pre-excitation in Wolff Parkinson White syndrome in the aged]. / La pre-eccitazione ventricolare da sindrome di Wolff Parkinson white nell'anziano.

AIM: To evaluate any differences in ventricular pre-excitation secondary to Wolff Parkinson White syndrome in the aged compared to young and adult patients. EXPERIMENTAL DESIGN: a clinical study was performed using a comparative prospective criterion with retrospective analysis. The duration of follow-up ranged between one and ten years. SETTING: the series was collected from the Cardiology Clinic of the Health District and the Cardiology Division of Gorizia, both forming part of no. 2 Isontina Health Service. PATIENTS OR PARTICIPANTS: the series included 17 patients suffering from Wolff Parkinson White syndrome who were divided into two study groups: 9 elderly patients and 8 young patients. The latter were subdivided into a first subgroup of 4 cases with Wolff Parkinson White syndrome with ECG positive for the presence of delta waves, and a second subgroup also with Wolff Parkinson White syndrome secondary to bundle. INTERVENTIONS: some young patients with Wolff Parkinson White syndrome who were symptomatic for tachycardia underwent ablative surgery with radiofrequency of the bundle. PARAMETERS: all patients underwent cardiological screening focused in particular on surface electrocardiogram. Those cases with Wolff-Parkinson White syndrome with occult bundle underwent transesophageal electrostimulation to find the conduction threshold of the anomalous bundle. RESULTS: Adult-elderly patients: six subjects were diagnosed with antero-septal and left ventricular Kent's bundle (type B common) and 3 cases with Mahaim-Wiston bundle (type A rare). Surface ECG revealed the presence of left ventricular hypertrophy in 6 cases, left anterior hemiblock and total block of the left branch in 3 cases, as well as myocardial pseudonecrosis correlated to Wolff Parkinson White syndrome. Young patients: four out of this group were affected by Kent's bundle with type B Wolff Parkinson White syndrome and the same number suffered from the same syndrome caused by occult bundle. Patients in the first subgroup showed an antero-septal, transitional and left ventricular orientation of Kent's bundle, with the onset of 2 cases of orthodromic and antidromic reciprocal rhythm respectively and 1 case of atrial fibrillation. The refractory nature of the anomalous pathway was not very high in 2 cases, equal to 60 milliseconds and 240 milliseconds with the proposed ablation of the anomalous bundle.