Model of unidirectional block formation leading to reentrant ventricular tachycardia in the infarct border zone of postinfarction canine hearts

AbstractBackgroundWhen the infarct border zone is stimulated prematurely, a unidirectional block line (UBL) can form and lead to double-loop (figure-of-eight) reentrant ventricular tachycardia (VT) with a central isthmus. The isthmus is composed of an entrance, center, and exit. It was hypothesized that for certain stimulus site locations and coupling intervals, the UBL would coincide with the isthmus entrance boundary, where infarct border zone thickness changes from thin-to-thick in the travel direction of the premature stimulus wavefront.MethodA quantitative model was developed to describe how thin-to-thick changes in the border zone result in critically convex wavefront curvature leading to conduction block, which is dependent upon coupling interval. The model was tested in 12 retrospectively analyzed postinfarction canine experiments. Electrical activation was mapped for premature stimulation and for the first reentrant VT cycle. The relationship of functional conduction block forming during premature stimulation to functional block during reentrant VT was quantified.ResultsFor an appropriately placed stimulus, in accord with model predictions: 1. The UBL and reentrant VT isthmus lateral boundaries overlapped (error: 4.8±5.7mm). 2. The UBL leading edge coincided with the distal isthmus where the center-entrance boundary would be expected to occur. 3. The mean coupling interval was 164.6±11.0ms during premature stimulation and 190.7±20.4ms during the first reentrant VT cycle, in accord with model calculations, which resulted in critically convex wavefront curvature and functional conduction block, respectively, at the location of the isthmus entrance boundary and at the lateral isthmus edges.DiscussionReentrant VT onset following premature stimulation can be explained by the presence of critically convex wavefront curvature and unidirectional block at the isthmus entrance boundary when the premature stimulation interval is sufficiently short. The double-loop reentrant circuit pattern is a consequence of wavefront bifurcation around this UBL followed by coalescence, and then impulse propagation through the isthmus. The wavefront is blocked from propagating laterally away from the isthmus by sharp increases in border zone thickness, which results in critically convex wavefront curvature at VT cycle lengths

Challenges associated with interpreting mechanisms of AF

Determining optimal treatment strategies for complex arrhythmogenesis in AF is confounded by the lack of consensus regarding the mechanisms causing AF. Studies report different mechanisms for AF, ranging from hierarchical drivers to anarchical multiple activation wavelets. Differences in the assessment of AF mechanisms are likely due to AF being recorded across diverse models using different investigational tools, spatial scales and clinical populations. The authors review different AF mechanisms, including anatomical and functional re-entry, hierarchical drivers and anarchical multiple wavelets. They then describe different cardiac mapping techniques and analysis tools, including activation mapping, phase mapping and fibrosis identification. They explain and review different data challenges, including differences between recording devices in spatial and temporal resolutions, spatial coverage and recording surface, and report clinical outcomes using different data modalities. They suggest future research directions for investigating the mechanisms underlying human AF

Contribution of tocols to food Sensorial properties, stability, and overall quality

This paper reviews the contribution of tocopherols and tocotrienols (tocols) to food quality as well as their bioactivity and health-promoting properties, which have attracted researchers and food technologists. Tocols are lipophilic phenolic antioxidants encompassing tocopherols that are characterized by a saturated side chain and tocotrienols with an unsaturated isoprenoid side chain. Tocols are natural constituents of several foods like dairy, vegetable oils, nuts, and grains. Their presence in foods, namely, as food additives, helps prevent lipid oxidation, which negatively affects the sensorial quality of foods, and even the nutritional value and safety. Supplementation of animals’ diets with tocopherols has proven its effectiveness in preserving fresh color and flavor of the meat. Although alfa-tocopherol displays much higher vitamin E activity than other tocols, health outcomes have been reported for tocotrienols, thus calling for more studies.info:eu-repo/semantics/publishedVersio

Slow uniform electrical activation during sinus rhythm is an indicator of reentrant VT isthmus location and orientation in an experimental model of myocardial infarction.

BACKGROUND: To validate the predictability of reentrant circuit isthmus locations without ventricular tachycardia (VT) induction during high-definition mapping, we used computer methods to analyse sinus rhythm activation in experiments where isthmus location was subsequently verified by mapping reentrant VT circuits. METHOD: In 21 experiments using a canine postinfarction model, bipolar electrograms were obtained from 196-312 recordings with 4mm spacing in the epicardial border zone during sinus rhythm and during VT. From computerized electrical activation maps of the reentrant circuit, areas of conduction block were determined and the isthmus was localized. A linear regression was computed at three different locations about the reentry isthmus using sinus rhythm electrogram activation data. From the regression analysis, the uniformity, a measure of the constancy at which the wavefront propagates, and the activation gradient, a measure that may approximate wavefront speed, were computed. The purpose was to test the hypothesis that the isthmus locates in a region of slow uniform activation bounded by areas of electrical discontinuity. RESULTS: Based on the regression parameters, sinus rhythm activation along the isthmus near its exit proceeded uniformly (mean r2= 0.95±0.05) and with a low magnitude gradient (mean 0.37±0.10mm/ms). Perpendicular to the isthmus long-axis across its boundaries, the activation wavefront propagated much less uniformly (mean r2= 0.76±0.24) although of similar gradient (mean 0.38±0.23mm/ms). In the opposite direction from the exit, at the isthmus entrance, there was also less uniformity (mean r2= 0.80±0.22) but a larger magnitude gradient (mean 0.50±0.25mm/ms). A theoretical ablation line drawn perpendicular to the last sinus rhythm activation site along the isthmus long-axis was predicted to prevent VT reinduction. Anatomical conduction block occurred in 7/21 experiments, but comprised only small portions of the isthmus lateral boundaries; thus detection of sinus rhythm conduction block alone was insufficient to entirely define the VT isthmus. CONCLUSIONS: Uniform activation with a low magnitude gradient during sinus rhythm is present at the VT isthmus exit location but there is less uniformity across the isthmus lateral boundaries and at isthmus entrance locations. These factors may be useful to verify any proposed VT isthmus location, reducing the need for VT induction to ablate the isthmus. Measured computerized values similar to those determined herein could therefore be assistive to sharpen specificity when applying sinus rhythm mapping to localize EP catheter ablation sites

Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

The advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase, 5HT3 antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK1 antagonists) belong to a new class of antiemetic agents that specifically target the NK1 receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK1 antagonists to dual therapy with a 5HT3 antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled

Retrograde semaphorin-plexin signalling drives homeostatic synaptic plasticity.

Homeostatic signalling systems ensure stable but flexible neural activity and animal behaviour. Presynaptic homeostatic plasticity is a conserved form of neuronal homeostatic signalling that is observed in organisms ranging from Drosophila to human. Defining the underlying molecular mechanisms of neuronal homeostatic signalling will be essential in order to establish clear connections to the causes and progression of neurological disease. During neural development, semaphorin-plexin signalling instructs axon guidance and neuronal morphogenesis. However, semaphorins and plexins are also expressed in the adult brain. Here we show that semaphorin 2b (Sema2b) is a target-derived signal that acts upon presynaptic plexin B (PlexB) receptors to mediate the retrograde, homeostatic control of presynaptic neurotransmitter release at the neuromuscular junction in Drosophila. Further, we show that Sema2b-PlexB signalling regulates presynaptic homeostatic plasticity through the cytoplasmic protein Mical and the oxoreductase-dependent control of presynaptic actin. We propose that semaphorin-plexin signalling is an essential platform for the stabilization of synaptic transmission throughout the developing and mature nervous system. These findings may be relevant to the aetiology and treatment of diverse neurological and psychiatric diseases that are characterized by altered or inappropriate neural function and behaviour