Anthropomorphic simulator for minimally invasive epicardial access procedures

We have developed a prototype, in?vitro anthropomorphic model for simulating pressure-guided, subxiphoid access procedures done to enable minimally invasive epicardial cardiac procedures including treatments for ventricular tachycardia. Life-size replicas of the heart and lungs were modelled using anatomically accurate surrogates. The dynamic pressure–frequency profiles of simulated pericardial fluid surrounding the water-pumped replica heart were measured and validated against previously acquired human intrapericardial pressure observations (Pearson's r?=?0.88, p?<?0.001). In replicating access procedures for approaching and entering the pericardial space, the system produced physiologically appropriate pressure measurements at each intermediate point along the needle's insertion pathway. Details of construction and performance are presented and discussed.     

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.     

The characteristics of the lobular arrangement indicate the dynamic role played by the infrapatellar fat pad in knee kinematics

The infrapatellar fat pad (IFP) is an intracapsular but extrasynovial structure, located between the patellar tendon, the femoral condyles and the tibial plateau. It consists of white adipose tissue, organised in lobules defined by thin connective septa. The aim of this study is the morphometric and ultrasonographic analysis of IFP in subjects without knee pathology during flexion‐extension movements. The morphometric study was conducted on 20 cadavers (15M, 5F, mean age 80.2 years). Ultrasound was performed on 24 volunteers with no history of knee diseases (5M, 19F, mean age: 45 years). The characteristics of the adipose lobules near the patellar tendon and in the deep portion of the IFP were evaluated. Numerical models were provided, according to the size of the lobules. At histological examination, the adipose lobules located near the patellar tendon were larger (mean area 12.2 mm² ± 5.3) than those at a deeper level (mean area 1.34 mm² ± 0.7, P < 0.001) and the thickness of the septa of the deepest adipose lobules (mean value 0.35 mm ± 0.32) was greater than that of the superficial one (mean value 0.29 mm ± 0.25, P < 0.001). At ultrasound, the IFP was seen to be composed of very large lobules in the superficial part (mean area 0.29 cm² ± 0.17 in extension), with a significant reduction in flexion (mean area 0.12 cm² ± 0.07, P < 0.01). The deep lobules were smaller (mean area 0.11 cm² ± 0.08 in extension) and did not change their values (mean area 0.19 cm² ± 0.52 in flexion, P > 0.05). In the sagittal plane, the reduction of thickness of the superficial layer (with large adipose lobules) during flexion was 20.6%, whereas that of the deep layer (with small adipose lobules) was 1.3%. Numerical simulation of vertical loads, corresponding to flexion of the knee, showed that stress mainly developed within the interlobular septa and opposed bulging of the lobules. The characteristics of the lobular arrangement of the IFP (large lobules with superficial septa in the superficial part and small lobules with thick septa in the deep one), significant changes in the areas and perimeters of the superficial lobules, and the reduced thickness of the superficial layer during flexion all indicate the dynamic role played by the IFP in knee kinematics.     

Separation of early afterdepolarizations from arrhythmogenic substrate in the isolated perfused hypokalaemic murine heart through modifiers of calcium homeostasis

Aims: We resolved roles for early afterdepolarizations (EADs) and transmural gradients of repolarization in arrhythmogenesis in Langendorff‐perfused hypokalaemic murine hearts paced from the right ventricular epicardium. Methods: Left ventricular epicardial and endocardial monophasic action potentials (MAPs) and arrhythmogenic tendency were compared in the presence and absence of the L‐type Ca²⁺ channel blocker nifedipine (10 nm –1 μm ) and the calmodulin kinase type II inhibitor KN‐93 (2 μm ). Results: All the hypokalaemic hearts studied showed prolonged epicardial and endocardial MAPs, decreased epicardial‐endocardial APD₉₀ difference, EADs, triggered beats and ventricular tachycardia (VT) (n = 6). In all spontaneously beating hearts, 100 (but not 10) nm nifedipine reduced both the incidence of EADs and triggered beats from 66.9 ± 15.7% to 28.3 ± 8.7% and episodes of VT from 10.8 ± 6.3% to 1.2 ± 0.7% of MAPs (n = 6 hearts, P < 0.05); 1 μm nifedipine abolished all these phenomena (n = 6). In contrast programmed electrical stimulation (PES) still triggered VT in six of six hearts with 0, 10 and 100 nm but not 1 μm nifedipine. 1 μm nifedipine selectively reduced epicardial (from 66.1 ± 3.4 to 46.2 ± 2.5 ms) but not endocardial APD₉₀, thereby restoring ΔAPD₉₀ from ?5.9 ± 2.5 to 15.5 ± 3.2 ms, close to normokalaemic values. KN‐93 similarly reduced EADs, triggered beats and VT in spontaneously beating hearts to 29.6 ± 8.9% and 1.7 ± 1.1% respectively (n = 6) yet permitted PES‐induced VT (n = 6), in the presence of a persistently negative ΔAPD₉₀. Conclusions: These findings empirically implicate both EADs and triggered beats alongside arrhythmogenic substrate of ΔAPD₉₀ in VT pathogenesis at the whole heart level.     

Influence of body mass index and weight lifting on bicep brachii muscle and distal bicep tendon stiffness evaluated using ultrasound elastography

Background

There is an increased interest in quantifying and characterizing epicardial fat which has been linked to various cardiovascular diseases such as coronary artery disease and atrial fibrillation. Recently, three-dimensional single-phase Dixon techniques have been used to depict the heart and to quantify the surrounding fat. The purpose of this study was to investigate the merits of a new high-resolution cine 3D Dixon technique for quantification of epicardial adipose tissue and compare it to single-phase 3D Dixon in patients with cardiovascular disease.

Methods

Fifteen patients referred for clinical CMR examination of known or suspected heart disease were scanned on a 1.5 T scanner using single-phase Dixon and cine Dixon. Epicardial fat was segmented by three readers and intra- and inter-observer variability was calculated per slice. Cine Dixon segmentation was performed in the same cardiac phase as single-phase Dixon. Subjective image quality assessment of water and fat images were performed by three readers using a 4-point Likert scale (1 = severe; 2 = significant; 3 = mild; 4 = no blurring of cardiac structures).

Results

Intra-observer variability was excellent for cine Dixon images (ICC = 0.96), and higher than single-phase Dixon (ICC = 0.92). Inter-observer variability was good for cine Dixon (ICC = 0.76) and moderate for single-phase Dixon (ICC = 0.63). The intra-observer measurement error (mean ± standard deviation) per slice for cine was − 0.02 ± 0.51 ml (− 0.08 ± 0.4%), and for single-phase 0.39 ± 0.72 ml (0.18 ± 0.41%). Inter-observer measurement error for cine was 0.46 ± 0.98 ml (0.11 ± 0.46%) and for single-phase 0.42 ± 1.53 ml (0.17 ± 0.47%). Visual scoring of the water image yielded median of 2 (interquartile range = [Q3-Q1] 2–2) for cine and median of 3 (interquartile range = 3–2) for single-phase (P < 0.05) while no significant difference was found for the fat images, both techniques yielding a median of 3 and interquartile range of 3–2.

Conclusion

Cine Dixon can be used to quantify epicardial fat with lower intra- and inter-observer variability compared to standard single-phase Dixon. The time-resolved information provided by the cine acquisition appears to support the delineation of the epicardial adipose tissue depot.

     

Pharmacological separation of early afterdepolarizations from arrhythmogenic substrate in DeltaKPQ Scn5a murine hearts modelling human long QT 3 syndrome

Aim: To perform an empirical, pharmacological, separation of early afterdepolarizations (EADs) and transmural gradients of repolarization in arrhythmogenesis in a genetically modified mouse heart modelling human long QT syndrome (LQT) 3. Methods: Left ventricular endocardial and epicardial monophasic action potentials and arrhythmogenic tendency were compared in isolated wild type (WT) and Scn5a+/Δ hearts perfused with 0.1 and 1 μm propranolol and paced from the right ventricular epicardium. Results: All spontaneously beating bradycardic Scn5a+/Δ hearts displayed EADs, triggered beats and ventricular tachycardia (VT; n = 7), events never seen in WT hearts (n = 5). Perfusion with 0.1 and 1 μm propranolol suppressed all EADs, triggered beats and episodes of VT. In contrast, triggering of VT persisted following programmed electrical stimulation in 6 of 12 (50%), one of eight (12.5%), but six of eight (75%) Scn5a+/Δ hearts perfused with 0, 0.1 and 1 μm propranolol respectively in parallel with corresponding alterations in repolarization gradients, reflected in action potential duration (ΔAPD₉₀) values. Thus 0.1 μm propranolol reduced epicardial but not endocardial APD₉₀ from 54.7 ± 1.6 to 44.0 ± 2.0 ms, restoring ΔAPD₉₀ from ?3.8 ± 1.6 to 3.5 ± 2.5 ms (all n = 5), close to WT values. However, 1 μm propranolol increased epicardial APD₉₀ to 72.5 ± 1.2 ms and decreased endocardial APD₉₀ from 50.9 ± 1.0 to 24.5 ± 0.3 ms, increasing ΔAPD₉₀ to ?48.0 ± 1.2 ms. Conclusion: These findings empirically implicate EADs in potentially initiating spontaneous arrhythmogenic phenomena and transmural repolarization gradients in the re‐entrant substrate that would sustain such activity when provoked by extrasystolic activity in murine hearts modelling human LQT3 syndrome.     

心外膜脂肪组织转染人apM1基因抑制兔冠状动脉粥样硬化的形成**☆

背景：心外膜脂肪分泌的脂联素水平下降可能是导致冠状动脉粥样硬化的主要原因之一。 目的：观察人脂联素基因apM1转染至兔心外膜脂肪组织对高脂喂食兔冠状动脉粥样硬化形成的影响。 方法：向兔心包腔内注射脂质体包裹的pEGFP-apM1重组质粒50 μL,分别于注射后2,7,28 d观察转染效率。采用高脂喂食方法制备兔冠状动脉粥样硬化模型,并按上述方法转染apM1基因,于转染后4周取材。 结果与结论：心包腔内转染apM1基因2 d后即可检测到兔心外膜脂肪组织apM1基因高表达,并可持续至28 d。心外膜脂肪转染apM1基因对高脂喂食引起的外周血脂联素、肿瘤坏死因子α、总胆固醇、高密度脂蛋白胆固醇及低密度脂蛋白胆固醇水平无显著影响,但可使心包腔液中脂联素水平显著增加、肿瘤坏死因子α水平显著降低(P < 0.01),冠状动脉内膜/中膜厚度比减小40.66%。说明经心包腔注射可将apM1基因有效转染入心外膜脂肪组织,并可在局部通过抑制高脂诱导的炎性因子释放而抑制冠状动脉粥样硬化的形成。     

Direct vision in minimally invasive epicardial procedures: preliminary tests of prototype instrumentation

Abstract

This study investigated the use of direct visualization to enhance minimally invasive epicardial procedures. A commercially available miniature camera was placed in a prototype subxiphoid introducer needle and bench top, in vitro and in vivo tests of system performance were made during simulated and actual attempts at pericardial access and cardio-endoscopy. This system had an unshielded field of view of 100° and a resolution of 220?×?224 pixels. When a sleeve used to maintain depth of field was slid past the distal tip of the camera probe, the field of view would decrease by ≈15° per millimetre of sleeve extension, but without loss of image quality. While tests during in vivo subxiphoid access in a porcine model revealed that the pericardial membrane was difficult to localize, the results also showed excellent resolution of the coronary arteries on the epicardial surface. These findings and potential improvements are discussed in detail.     

Application of L1-Norm Regularization to Epicardial Potential Solution of the Inverse Electrocardiography Problem

The electrocardiographic inverse problem of computing epicardial potentials from multi-electrode body-surface ECG measurements, is an ill-posed problem. Tikhonov regularization is commonly employed, which imposes penalty on the L2-norm of the potentials (zero-order) or their derivatives. Previous work has indicated superior results using L2-norm of the normal derivative of the solution (a first order regularization). However, L2-norm penalty function can cause considerable smoothing of the solution. Here, we use the L1-norm of the normal derivative of the potential as a penalty function. L1-norm solutions were compared to zero-order and first-order L2-norm Tikhonov solutions and to measured ‘gold standards’ in previous experiments with isolated canine hearts. Solutions with L1-norm penalty function (average relative error [RE] = 0.36) were more accurate than L2-norm (average RE = 0.62). In addition, the L1-norm method localized epicardial pacing sites with better accuracy (3.8 ± 1.5 mm) compared to L2-norm (9.2 ± 2.6 mm) during pacing in five pediatric patients with congenital heart disease. In a pediatric patient with Wolff–Parkinson–White syndrome, the L1-norm method also detected and localized two distinct areas of early activation around the mitral valve annulus, indicating the presence of two left-sided pathways which were not distinguished using L2 regularization.     

Quantification of the triglyceride fatty acid composition with 3.0 T MRI

The aim of this work was to validate a sequential method for quantifying the triglyceride fatty acid composition with 3.0 T MRI. The image acquisition was performed with a 3D spoiled gradient multiple echo sequence. A specific phase correction algorithm was implemented to correct the native phase images for wrap, zero‐ and first‐order phase and rebuild the real part images. Then, using a model of a fat ¹H MR spectrum integrating nine components, the number of double bonds (ndb) and the number of methylene‐interrupted double bonds (nmidb) were derived. The chain length (CL) was obtained from these parameters using heuristic approximation. Validations were performed on different vegetable oils whose theoretical fatty acid composition was used as reference and in five human subjects. In vivo measurements were made in the liver and in the subcutaneous and visceral adipose tissues. Linear regressions showed strong correlations between ndb and nmidb quantified with MRI and the theoretical values calculated using oil composition. Mean ndb/nmidb/CL were 1.80 ± 0.25/0.51 ± 0.21/17.43 ± 0.07, 2.72 ± 0.31/0.94 ± 0.16/17.47 ± 0.08 and 2.53 ± 0.21/0.84 ± 0.14/17.43 ± 0.07 in the liver, subcutaneous and visceral adipose tissues respectively. The results suggest that the triglyceride fatty acid composition can be assessed in human fatty liver and adipose tissues with a clinically relevant MRI method at 3.0 T. Copyright © 2014 John Wiley & Sons, Ltd.     

In vivo evaluation of the improved MCMS-0102 pacemaker with a rapid pacing mode for induction of experimental heart failure in animals

The MCMS-0102 cardiac pacemaker for rapid ventricular pacing to induce heart failure in animals has been improved in terms of miniaturization and performance. To determine the performance of the new MCMS-0102, six devices were implanted in beagle dogs, and two of these devices were reimplanted for continued pacing in a total of eight beagle dogs. The hearts were paced at 260 beats per minute for 4 weeks (P group: n = 8). The hemodynamic status of the P group was examined and compared with nonpaced dogs (NP group: n = 8). The neurohumoral status of the P group was evaluated before and after rapid pacing. Stable operation of the six devices during rapid pacing was confirmed using the telemetry system. Postmortem examinations revealed features similar to clinical heart failure characterized by massive ascites, pleural effusion, cardiomegaly, and liver congestion in all the paced dogs. Cardiac output was 1.1 ± 0.2 l/min in the NP group and 0.5 ± 0.1 l/min in the P group (P < 0.0001). The left atrial pressure and the central venous pressure of the P group and the NP group were 23 ± 6 versus 6 ± 2 mmHg (P < 0.0001) and 10 ± 3 versus 4 ± 3 mmHg (P < 0.001), respectively. In the paced dogs, plasma renin activity increased from 0.5 ± 0.4 to 8.5 ± 7.4 ng/ml/h (P < 0.05) and atrial natriuretic peptide levels increased from 69 ± 41 to 229 ± 72 pg/ml (P < 0.001). The improved MCMS-0102 was successfully implanted in beagle dogs and it succeeded in inducing the congestive heart failure model.     

Clinical structural anatomy of the inferior pyramidal space reconstructed from the living heart: Three‐dimensional visualization using multidetector‐row computed tomography

The inferior pyramidal space (IPS) comprises the epicardial visceral adipose tissue wedged between the bottoms of the four cardiac chambers from the postero‐inferior epicardial surface of the heart. Understanding the complex anatomy around the IPS is important for clinical cardiologists. Although leading anatomists and radiologists have clarified the anatomy of the IPS in detail, few studies have demonstrated this anatomy in three dimensions. The aim of this study was to visualize the three‐dimensional anatomy of the IPS reconstructed from the living heart using multidetector‐row computed tomography. We also developed an original paper model of the IPS to enhance understanding of its intricate structure. Clin. Anat. 28:878–887, 2015. © 2014 Wiley Periodicals, Inc.     

An anatomical comparison of the fasciae of the thigh: A macroscopic,microscopic and ultrasound imaging study

Although the number of Ultrasound (US) imaging studies investigating the fascial layers are becoming more numerous, the majority tend to use different reference points and terminology to describe their findings. The current work set out to compare macroscopic and microscopic data of specimens of the fascial layers of the thigh with US imaging findings. Specimens of the different fascial layers of various regions of the thigh were collected for macroscopic and histological analyses from three fresh cadavers and compared with in vivo US images of the thighs of 20 healthy volunteers. The specimens showed that the subcutaneous tissue of the thigh is made up of three layers: a superficial adipose layer, a membranous layer/superficial fascia, and a deep adipose layer. The deep fascia is composed of an aponeurotic fascia, which envelops all the thigh muscles and is laterally reinforced by the iliotibial tract and an epimysial fascia, which is specific for each muscle. The morphometric measurements of the thickness of the superficial fascia were different (anterior: 153.2 ± 39.3 µm; medial: 128.4 ± 24.7 µm; lateral: 154 ± 28.9 µm; and posterior: 148.8 ± 33.2 µm) as were those of the deep fascia (anterior: 556.8 ± 176.2 µm; medial: 820.4 ± 201 µm; lateral: 1112 ± 237.9 µm; and posterior: 730.4 ± 186.5 µm). The US scans showed a clear picture of the superficial adipose tissue, the superficial fascia, and the deep adipose tissue, as well as the deep fasciae. The epimysial and aponeurotic fasciae of only some topographic areas could be independently identified. The US imaging findings confirmed that the superficial and deep fascia have different thicknesses, and they showed that the US measurements were always larger with respect to those produced by histological analysis (p < 0.001) probably due to shrinkage during the processing. The posterior region (level 1) of the superficial fascia had, for example, a mean thickness of 0.56 ± 0.12 mm at US, while the histological analysis showed that it was 148.8 ± 33.2 µm. Showing a similar pattern, the thickness of the deep fascia was as follows: 1.64 ± 0.85 mm versus 730.4 ± 186.5 µm. Study results have confirmed that US can be considered a valid, non-invasive instrument to evaluate the fascial layers. In any event, there is a clear need for a set of standardised protocols since the thickness of the fascial layers of different parts of the human body varies and the data obtained using inaccurate reference points are not reproducible or comparable. Given the inconsistent terminology used to describe the fascial system, it would also be important to standardise the terminology used to define its parts. The difficulty in distinguishing between the epimysial and aponeurotic/deep fascia can also impede data interpretation.     

Three-dimensional simulation of epicardial potentials using a microcomputer-based heart-torso model

Previous cardiac simulation studies have focused on simulating the activation isochrones and subsequently the body surface potentials. Epicardial potentials, which are important for clinical applications as well as for electrocardiography inverse problem studies, however, have usually been neglected. This paper presents a procedure of simulating epicardial potentials using a microcomputer-based heart-torso model with real geometry. The heart model developed earlier which was composed of more than 60,000 cell units was used in this study. To simulate the epicardial potentials, an epicardial surface model which enclosed the whole heart was constructed. The heart model, together with the epicardial surface model, are mounted in an inhomogeneous human torso model. Electric dipoles, which are proportional to the spatial gradient of the action potential, are generated in all cell units. These dipoles give rise to a potential distribution on the epicardial surface, which is calculated by means of the boundary element method. The simulated epicardial potential maps during a normal heart beat and in patients with left bundle branch block (LBBB) are in close agreement with those reported in the literature.     

Electrophysiological determinants of hypokalaemia‐induced arrhythmogenicity in the guinea‐pig heart

Aim: Hypokalaemia is an independent risk factor contributing to arrhythmic death in cardiac patients. In the present study, we explored the mechanisms of hypokalaemia‐induced tachyarrhythmias by measuring ventricular refractoriness, spatial repolarization gradients, and ventricular conduction time in isolated, perfused guinea‐pig heart preparations. Methods: Epicardial and endocardial monophasic action potentials from distinct left ventricular (LV) and right ventricular (RV) recording sites were monitored simultaneously with volume‐conducted electrocardiogram (ECG) during steady‐state pacing and following a premature extrastimulus application at progressively reducing coupling stimulation intervals in normokalaemic and hypokalaemic conditions. Results: Hypokalaemic perfusion (2.5 mm K⁺ for 30 min) markedly increased the inducibility of tachyarrhythmias by programmed ventricular stimulation and rapid pacing, prolonged ventricular repolarization and shortened LV epicardial and endocardial effective refractory periods, thereby increasing the critical interval for LV re‐excitation. Hypokalaemia increased the RV‐to‐LV transepicardial repolarization gradients but had no effect on transmural dispersion of APD₉₀ and refractoriness across the LV wall. As determined by local activation time recordings, the LV‐to‐RV transepicardial conduction and the LV transmural (epicardial‐to‐endocardial) conduction were slowed in hypokalaemic heart preparations. This change was attributed to depressed diastolic excitability as evidenced by increased ventricular pacing thresholds. Conclusion: These findings suggest that hypokalaemia‐induced arrhythmogenicity is attributed to shortened LV refractoriness, increased critical intervals for LV re‐excitation, amplified RV‐to‐LV transepicardial repolarization gradients and slowed ventricular conduction in the guinea‐pig heart.     

Long‐TE 1H MRS suggests that liver fat is more saturated than subcutaneous and visceral fat

Cross‐talk between adipose tissue and liver is disturbed in the metabolic syndrome. Moreover, the relative fatty acid composition of adipose and liver fat is poorly characterized. Long‐TE ¹H MRS can determine the unsaturation and polyunsaturation of adipose tissue. The aim of this study was to use long‐TE ¹H MRS to determine the composition of liver fat and its relation to adipose tissue composition. Sixteen subjects with increased liver fat (>5%) were recruited for the study. Using TE = 200 ms, we were able to resolve the olefinic (?CH, 5.3 ppm) and water (H₂O, 4.7 ppm) resonances in liver spectra and to obtain a repeatable estimate of liver fat unsaturation (coefficient of variation, 2.3%). With TE = 135 ms, the diallylic (?C? CH₂? C?, 2.8 ppm) resonance was detectable in subjects with a liver fat content above 15%. Long‐TE ¹H MRS was also used to determine the unsaturation in subcutaneous (n = 16) and visceral (n = 11) adipose tissue in the same subjects. Liver fat was more saturated (double bonds per fatty acid chain, 0.812 ± 0.022) than subcutaneous (double bonds per fatty acid chain, 0.862 ± 0.022, p < 0.0004) or visceral (double bonds per fatty acid chain, 0.865 ± 0.033, p < 0.0004) fat. Liver fat unsaturation correlated with subcutaneous unsaturation (R = 0.837, p < 0.0001) and visceral unsaturation (R = 0.879, p < 0.0004). The present study introduces a new noninvasive method for the assessment of the composition of liver fat. The results suggest that liver fat is more saturated than subcutaneous or visceral adipose tissue, which may be attributed to differences in de novo lipogenesis. Copyright © 2010 John Wiley & Sons, Ltd.     

Effects of potassium channel openers in the isolated perfused hypokalaemic murine heart

Aim: We explored the anti‐arrhythmic efficacy of K⁺ channel activation in the hypokalaemic murine heart using NS1643 and nicorandil, compounds which augment I_Kr and I_KATP respectively. Methods: Left ventricular epicardial and endocardial monophasic action potentials were compared in normokalaemic and hypokalaemic preparations in the absence and presence of NS1643 (30 μm ) and nicorandil (20 μm ). Results: Spontaneously beating hypokalaemic hearts (3 mm K⁺) all elicited early afterdepolarizations (EADs) and episodes of ventricular tachycardia (VT). Perfusion with NS1643 and nicorandil suppressed EADs and VT in 7 of 13 and five of six hypokalaemic hearts. Provoked arrhythmia studies using programmed electrical stimulation induced VT in all hypokalaemic hearts, but failed to do so in 7 of 13 and five of six hearts perfused with NS1643 and nicorandil respectively. These anti‐arrhythmic effects were accompanied by reductions in action potential duration at 90% repolarization (APD₉₀) and changes in the transmural gradient of repolarization, reflected in ΔAPD₉₀. NS1643 and nicorandil reduced epicardial APD₉₀ from 68.3 ± 1.1 to 56.5 ± 4.1 and 51.5 ± 1.5 ms, respectively, but preserved endocardial APD₉₀ in hypokalaemic hearts. NS1643 and nicorandil thus restored ΔAPD₉₀ from ?9.6 ± 4.3 ms under baseline hypokalaemic conditions to 3.9 ± 4.1 and 9.9 ± 2.1 ms, respectively, close to normokalaemic values. Conclusion: These findings demonstrate, for the first time, the anti‐arrhythmic efficacy of K⁺ channel activation in the setting of hypokalaemia. NS1643 and nicorandil are anti‐arrhythmic through the suppression of EADs, reductions in APD₉₀ and restorations of ΔAPD₉₀.