The cardiac conduction system (CCS) is a set of specialized myocardial pathways that spontaneously generate and conduct impulses transmitting throughout the heart, and causing the coordinated contractions of all parts of the heart. A comprehensive understanding of the anatomical characteristics of the CCS in the heart is the basis of studying cardiac electrophysiology and treating conduction-related diseases. It is also the key of avoiding damage to the CCS during open heart surgery. How to identify and locate the CCS has always been a hot topic in researches. Here, we review the histological imaging methods of the CCS and the specific molecular markers, as well as the exploration for localization and visualization of the CCS. We especially put emphasis on the clinical application prospects and the future development directions of non-destructive imaging technology and real-time localization methods of the CCS that have emerged in recent years.
Objective To evaluate the feasibility of imaging the rat cardiac conduction system (CCS) using transaortic antegrade perfusion of Alexa Fluor 633-labeled antibodies targeting hyperpolarization-activated cyclic nucleotide-gated cation channel 4 (HCN4) and connexin (Cx). The study also sought to optimize antibody dosage, perfusion duration, and assess the photostability of the dye. Methods Ex vivo rat heart model with transaortic antegrade perfusion was established using 33 male SPF-grade Sprague-Dawley (SD) rats. Primary and secondary antibody solutions were sequentially perfused in an antegrade manner. After perfusion for predetermined durations, the atrioventricular junction was observed, and the fluorescence intensity of the corresponding area was recorded. Five dose-gradient groups (n=3 rats/group), five perfusion time-gradient groups (n=3 rats/group), and ten continuous LED light exposure time-gradient groups (using 3 rats prepared with a fixed dose and time) were established to observe and record regional fluorescence intensity. Standard immunofluorescence staining was performed on both paraffin and frozen sections for comparative histological analysis. Results A region of aggregated red fluorescent signal was observed in the atrioventricular junction. Following semi-quantitative fluorescence intensity analysis of HCN4/Cx43 and validation through comparative histology, this structure was identified as the atrioventricular node (AVN) region. The AVN-to-background fluorescence intensity ratio showed no statistically significant differences among groups with increasing antibody dosage (P>0.05). The ratio increased with longer antibody perfusion times. Furthermore, no statistically significant differences in the ratio were observed among groups with extended light exposure (P>0.05). Conclusion Transaortic antegrade perfusion of fluorescently labeled antibodies can successfully image the AVN within the CCS of ex vivo rat hearts. Increasing the antibody dosage does not significantly improve the AVN imaging effect. Longer antibody perfusion time results in better imaging quality of the AVN. The fluorescent dye maintains sufficient visualization of the AVN even after prolonged (8 h) exposure to light.
The mechanisms underlying the impact of metabolic syndrome on cognitive dysfunction in patients with schizophrenia remain unclear. The present study employed a two-factor factorial design to investigate the effects of metabolic syndrome on white matter microstructure in schizophrenia and its association with cognitive function. A total of 187 participants were included and classified into four groups based on the diagnoses of schizophrenia and metabolic syndrome: schizophrenia patients with metabolic syndrome (SZ-wMS), schizophrenia patients without metabolic syndrome, healthy controls with metabolic syndrome, and healthy controls without metabolic syndrome. Diffusion tensor imaging data were acquired. Using diffusion tensor model, fractional anisotropy (FA) was calculated to characterize the microstructural integrity of white matter. Peripheral metabolic indices and multiple domains of cognitive function were also assessed. The SZ-wMS group showed further reduced FA in the right sagittal stratum. Within the two-factor analytical framework, an interaction effect between metabolic syndrome and schizophrenia on FA in the right sagittal stratum was identified. Correlation analyses revealed that reduced FA in the right sagittal stratum was associated with impaired language function in patients with schizophrenia. Moreover, mediation analysis indicated that body mass index might indirectly affect language function by influencing FA in the right sagittal stratum. In summary, reduced integrity of white matter fibers in sagittal stratum may represent a potential neural mechanism underlying the comorbidity of schizophrenia and metabolic syndrome and may be associated with language dysfunction in schizophrenia.