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Aims: Anatomical re-entry is an important mechanism of ventricular tachycardia, characterized by circular electrical propagation in a fixed pathway. It's current investigative and therapeutic approaches are non-biological, rather unspecific (drugs), traumatizing (electrical shocks), or irreversible (ablation). Optogenetics is a new biological technique that allows reversible modulation of electrical function with unmatched spatiotemporal precision using light-gated ion channels. We therefore investigated optogenetic manipulation of anatomical re-entry in ventricular cardiac tissue. Methods and results: Transverse, 150-μm-thick ventricular slices, obtained from neonatal rat hearts, were genetically modified with lentiviral vectors encoding Ca2+-translocating channelrhodopsin (CatCh), a light-gated depolarizing ion channel, or enhanced yellow fluorescent protein (eYFP) as control. Stable anatomical re-entry was induced in both experimental groups. Activation of CatCh was precisely controlled by 470-nm patterned illumination, while the effects on anatomical re-entry were studied by optical voltage mapping. Regional illumination in the pathway of anatomical re-entry resulted in termination of arrhythmic activity only in CatCh-expressing slices by establishing a local and reversible, depolarization-induced conduction block in the illuminated area. Systematic adjustment of the size of the lightexposed area in the re-entrant pathway revealed that re-entry could be terminated by either wave collision or extinction, depending on the depth (transmurality) of illumination. In silico studies implicated source-sink mismatches at the site of subtransmural conduction block as an important factor in re-entry termination. Conclusions: Anatomical re-entry in ventricular tissue can be manipulated by optogenetic induction of a local and reversible conduction block in the re-entrant pathway, allowing effective re-entry termination. These results provide distinctively new mechanistic insight into re-entry termination and a novel perspective for cardiac arrhythmia management. [ABSTRACT FROM AUTHOR]

Aims: Premature ventricular complexes (PVCs) due to spontaneous calcium (Ca) release (SCR) events at the cell level can precipitate ventricular arrhythmias. However, the mechanistic link between SCRs and PVC formation remains incompletely understood. The aim of this study was to investigate the conditions under which delayed afterdepolarizations resulting from stochastic subcellular SCR events can overcome electrotonic source-sink mismatch, leading to PVC initiation. Methods and results: A stochastic subcellular-scale mathematical model of SCR was incorporated in a realistic model of the rabbit ventricles and Purkinje system (PS). Elevated levels of diastolic sarcoplasmic reticulum Ca2+ (CaSR) were imposed until triggered activity was observed, allowing us to compile statistics on probability, timing, and location of PVCs. At CaSR= 1500 µmol/L PVCs originated in the PS. When SCR was incapacitated in the PS, PVCs also emerged in the ventricles, but at a higher CaSR (=1550 µmol/L) and with longer waiting times. For each model configuration tested, the probability of PVC occurrence increased from 0 to 100% within a well-defined critical CaSR range; this transition was much more abrupt in organ-scale models (~50 µmol/L CaSR range) than in the tissue strand (~100 µmol/L) or single-cell (~450 µmol/L) models. Among PVCs originating in the PS, ~68% were located near Purkinje-ventricular junctions (<1 mm). Conclusion: SCR events overcome source-sink mismatch to trigger PVCs at a critical CaSR threshold. Above this threshold, PVCs emerge due to increased probability and reduced variability in timing of SCR events, leading to significant diastolic depolarization. Sites of lower electronic load, such as the PS, are preferential locations for triggering. [ABSTRACT FROM AUTHOR]

OBJECTIVES In clinical practice, maximum diameter is used as a criterion to estimate aneurysm-rupture risk; however, it is only a general indicator and its value becomes difficult to estimate in the thoracic segment. Improved understanding of aortic aneurysm complexity and biomechanics is needed to achieve advancements in surgical repair techniques. The objective of this study was to determine the maximum wall stress by using imaging-derived data and a specific probabilistic design integrated into finite element (FE) analysis. METHODS Computed tomography images of thoracic aortic aneurysms from our database were analysed and the main morphological features were identified by means of a specific automatic routine. Morphological data were used to develop an idealized finite element library of thoracic aortic arch models. Sensitivity analyses were performed by using the geometrical parameters as input variables for a statistical wall stress assessment. Numerical results were compared with those obtained from deterministic analysis on patient-specific three-dimensional reconstructions. RESULTS The results showed that in small aneurysms, wall stress values similar to those of large aneurysms can be obtained if a significant eccentricity is achieved. In small aneurysms, the peak stress is primarily affected by the eccentricity of the bulge [correlation coefficient (CC) = 0.86], while for diameters in the range of 50–60 mm, the CC is 0.43 for the eccentricity and 0.72 for the maximum diameter. CONCLUSIONS The stress distribution in small aneurysms may contribute to the pathogenesis of aortic rupture and dissections. Our method can provide a novel and efficient procedure for generating computational models to estimate the wall stress in a comparative multivariate manner. [ABSTRACT FROM PUBLISHER]