Journal of Cardiovascular Translational Research

This study evaluates needleless liquid jet method and compares it with three common experimental methods: (1) intramuscular injection (IM), (2) left ventricular intracavitary infusion (LVIC), and (3) LV intracavitary infusion with aortic and pulmonary occlusion (LVIC-OCCL). Two protocols were executed. First (n = 24 rats), retention of dye was evaluated 10 min after delivery in an acute model. The acute study revealed the following: significantly higher dye retention (expressed as % myocardial cross-section area) in the left ventricle in both the liquid jet [52 ± 4] % and LVIC-OCCL [58 ± 3] % groups p < 0.05 compared with IM [31 ± 8] % and LVIC [35 ± 4] %. In the second (n = 16 rats), each animal received adeno-associated virus encoding green fluorescent protein (AAV.EGFP) at a single dose with terminal 6-week endpoint. In the second phase with AAV.EGFP at 6 weeks post-delivery, a similar trend was found with liquid jet [54 ± 5] % and LVIC-OCCL [60 ± 8] % featuring more LV expression as compared with IM [30 ± 9] % and LVIC [23 ± 9] %. The IM and LVIC-OCCL cross sections revealed myocardial fibrosis. With more detailed development in future model studies, needleless liquid jet delivery offers a promising strategy to improve direct myocardial delivery.

In this article, the available evidence about the functional effects of the contractile protein mutations that cause hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) is assessed. The molecular mechanism of the contractile apparatus of cardiac muscle and its regulation by Ca2+ and PKA phosphorylation have been extensively studied. Therefore, when a number of point mutations in the contractile protein genes were found to cause the well-defined phenotypes of HCM and DCM, it was expected that the diseases could be explained at the molecular level. However, the search for a distinctive molecular phenotype did not yield rapid results. Now that a substantial number of mutations that cause HCM or DCM have been investigated in physiologically relevant systems and with a range of experimental techniques, a pattern is emerging. In the case of HCM, the hypothesis that the major effect of mutations is to increase myofibrillar Ca2+-sensitivity seems to be well established, but the mechanisms by which an increase in myofibrillar Ca2+-sensitivity induces hypertrophy remain obscure. In contrast, DCM mutations are not correlated with a specific effect on Ca2+-sensitivity. It has recently been proposed that DCM mutations uncouple troponin I phosphorylation from Ca2+-sensitivity changes, albeit based on only a few mutations so far. A plausible link between uncoupling and DCM has been proposed via blunting of the response to α-adrenergic stimulation.

Over the last decades, tremendous advances have been made in understanding the genomic basis of a large number of chronic human diseases. Such advances were made possible by studying large numbers of patients over relatively long periods of time. It is increasingly recognized that acute robust stress stimulates pathways activated in chronic disease, facilitating mechanistic studies in much shorter time frames. A new field of molecular medicine, called perioperative genomics, uses robust surgical stress as a perturbation designed to explore such mechanisms. This new field is described briefly below.

Left ventricular (LV) remodeling and geometric patterns are associated with variations in prognosis. Two hundred twenty-eight patients who underwent selective isolated coronary artery bypass grafting (CABG) were included, divided into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy at baseline. More than half participants with normal geometry at baseline remained in that category, and similar ratio of concentric remodeling reverted to normal geometry on follow-up. The concentric hypertrophy at baseline tended to progress to eccentric geometry rather than normal geometry, while changes from eccentric to concentric hypertrophy was uncommon. iLVEDD had a significant association with an increased risk of developing an abnormal geometric pattern from a normal or concentric remodeling pattern, and iLVESD and LAScd involved in the regression from an abnormal geometric pattern. Thus, dynamic changes in LV geometric pattern are common on 1-year follow-up after CABG and LA strain has an incremental role for early detection in this process.

The endocannabinoid 2-arachidonoylglycerol (2-AG) is an inflammatory mediator and ligand for the cannabinoid receptors CB1 and CB2. We investigated the atherogenic mechanisms set in motion by 2-AG. Therefore, we created two atherosclerotic mouse models with distinct cell-specific knockouts of the CB2 receptor on either myeloid or endothelial cells. These mice were treated with JZL184, resulting in elevated plasma levels of 2-AG. After a high-fat high-cholesterol diet, atherosclerotic plaques were analyzed. The atherogenic effect of 2-AG was abrogated in mice lacking myeloid expression of the CB2 receptor but not in mice lacking endothelial expression of the CB2 receptor. In vitro, treatment of human monocytes with 2-AG led to the increased production of reactive oxygen species (ROS) and IL-1β. In conclusion, 2-AG shows an atherogenic effect in vivo, dependent on the presence of the CB2 receptor on myeloid cells. In addition, our in vitro data revealed 2-AG to promote inflammatory signalling in monocytes. 2-Arachidonoylglycerol shows an atherogenic effect that is abrogated in mice lacking myeloid expression of the CB2 receptor.

The aim of this study is to develop an automated deep-learning-based whole heart segmentation of ECG-gated computed tomography data. After 21 exclusions, CT acquired before transcatheter aortic valve implantation in 71 patients were reviewed and randomly split in a training (n = 55 patients), validation (n = 8 patients), and a test set (n = 8 patients). A fully automatic deep-learning method combining two convolutional neural networks performed segmentation of 10 cardiovascular structures, which was compared with the manually segmented reference by the Dice index. Correlations and agreement between myocardial volumes and mass were assessed. The algorithm demonstrated high accuracy (Dice score = 0.920; interquartile range: 0.906–0.925) and a low computing time (13.4 s, range 11.9–14.9). Correlations and agreement of volumes and mass were satisfactory for most structures. Six of ten structures were well segmented. Deep-learning-based method allowed automated WHS from ECG-gated CT data with a high accuracy. Challenges remain to improve right-sided structures segmentation and achieve daily clinical application.