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Background Neonatal murine hearts possess -for a brief period after birth- a robust capacity for spontaneous myocardial regeneration following cardiac injury. Whether hearts of neonatal large mammals possess similar regenerative potential is a matter of active investigation. Recently, two studies reported that 1-day-old and 2-day-old neonatal pigs exhibit a significant cardiac regenerative response post-myocardial infarction (MI), characterized by minimal cardiac fibrosis and spontaneous recovery of left ventricular (LV) function; this regenerative capacity is purportedly lost after the first two days of life. Purpose We sought to evaluate the regenerative potential of neonatal porcine hearts after MI. Methods Twenty-one neonatal farm pigs were randomly assigned to undergo MI by permanent ligation of the left anterior descending artery on postnatal day 1 (P1) or postnatal day 3 (P3). Infarcted P1 and P3 pigs were euthanized either at 1 week or at 7 weeks post-MI. Hearts explanted at 1 week post-MI underwent fluorescent immunohistochemistry for Ki67 and alpha-sarcomeric actinin to quantify myocyte cell cycle re-entry. Transthoracic echocardiography was performed at 7 weeks post-MI to quantify fractional shortening and systolic thickening of the anterior (infarcted) LV wall and the posterior (non-infarcted) LV wall. Hearts explanted at 7 weeks post-MI underwent staining with triphenyl-tetrazolium chloride and Masson's Trichrome to quantify infarct size, infarct circumference and infarct transmurality. Results Fourteen animals successfully completed the protocol. Infarct size (P1: 9.5±2.2% vs P3: 8.9±3.6% of LV, p=0.797), infarct circumference (P1: 33.8±7.1% vs P3: 29.8±10.6% of LV, p=0.566) and infarct transmurality (P1: 38.1±4.3% vs P3: 40.4±13.7% of anterior wall, p=0.764) were comparable in P1 and P3 animals at 7 weeks post-MI. LV fractional shortening (an index of global LV systolic function) was similar in P1 and P3 animals at 7 weeks post-MI (P1: 25.5±2.9% vs P3: 23.7±4.5%, p=0.662). Furthermore, systolic thickening in the anterior (infarcted) LV wall was depressed to a similar degree in P1 and P3 animals (P1: 31.8±5.3% vs P3: 32.3±8.5%, p=0.914) compared to systolic thickening in the posterior (non-infarcted) wall (P1: 72.5±9.0% vs P3: 69.0±11.4%, p=0.666) at 7 weeks post-MI. Myocyte cell cycle re-entry in the infarct border zone was increased in P1 animals compared to P3 animals (P1: 4.5±1.3 vs P3: 2.3±0.6 per field of view, p=0.045) at 1 week post-MI. Conclusions In contrast to recently-published reports, we did not observe a robust cardiac regenerative response in neonatal porcine hearts post-MI. Hearts of both 1-day-old and 3-day-old neonatal pigs exhibited substantial scarring and significant hypokinesia of the infarcted myocardium post-MI. Additional research is warranted to assess the cardiac regenerative potential of neonatal large mammals. Acknowledgement/Funding Co-financed by Greece and the European Union - European Social Fund

Aims Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart. Methods and Results In vitro, confluent lesions were reliably created by a ‘dielectrode’ catheter (energy delivered simultaneously (in parallel) from two 4mm electrodes spaced 1mm apart, towards an indifferent electrode), and a ‘bipolar’ catheter (energy delivered (in series) between two 4mm electrodes spaced 5mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30s duration (70°C) were administered to the inferior vena cava–tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length×width×depth measured 7·4 (2·4)×5·4 (2·2)×2·8 (0·8)mm in the standard unipolar mode, 10·2 (1·4)×6·3 (0·7)×3·3 (1·1)mm in the dielectrode mode and 14·0 (3·6)×6·0 (1·7)×3·8 (1·2)mm in the bipolar mode. Thus lesion length increased significantly through the three groups ( P

Purpose: T-wave abnormalities are used to identify risk for life-threatening arrhythmias. However, the exact genesis of the T-wave is still unclear. Therefore, we conducted an experimental study to correlate the ventricular repolarization pattern derived from intramural electrograms with the corresponding T-wave on the surface map. Methods: Pig hearts (n=9) were perfused according to Langendorff and paced from the atrium (cycle length 650 ms). Transmural needles (32-45 needles, 4 electrode terminals each) were inserted and local activation and repolarization times (AT and RT) were derived from unipolar electrograms. RT differences (maximum minus minimum) were determined along 4 anatomical axes: LV apico-basal, LV anterior-posterior, left-right ventricle and LV transmural. The hearts were immersed in a blood-filled container with 61 electrodes. From the simultaneously recorded electrograms, a pseudo body surface map (BSM) was derived. From the BSM the maximum T-wave duration was determined using the tangent method in the pseudo ECG with the largest T-wave amplitude. Results: Activation occurred earliest at the septum and latest at RV basal free wall and outflow tract, as in the human heart. Transmural activation was almost simultaneous, due to the transmural Purkinje network in the porcine heart. The T-wave in the body surface electrograms had a maximum duration of 93±4 ms (mean ± sem, n=9). In general, repolarization started at the septum and terminated at the left (LV) and right (RV) free walls. The maximum absolute temporal RT differences were: LV apico-basal (51±6 ms, n=9), LV anterior-posterior (51±9 ms, n=9) and between LV and RV (66±6 ms, n=9). The maximum absolute transmural RT difference in the LV was 34±7 ms (n=9). Latest minus earliest moment of repolarization within the hearts was 73±6 ms independent of axes. T-wave onset was always earlier (20±6 ms) than the minimum repolarization moment. T-wave end was similar to the maximum repolarization moment (0±3 ms). Conclusions: The major part of the electrocardiographic T-wave is explained by temporal repolarization differences across the entire heart, and not by only left-right, LV anterior-posterior, LV apico-basal or LV transmural RT differences. The discrepancy between T-wave onset and earliest RT may be explained by differences in action potential morphology.