Vagal nerve stimulation (VNS) has a meaningful basis as a potentially effective treatment for heart failure with reduced ejection fraction. There is an ongoing VNS randomized study, and four studies are completed. However, relatively little is known about the effect of acetylcholine (ACh) on repolarization in human ventricular cardiomyocytes, as well as the effect of ACh on the rapid component of the delayed rectifier K⁺ current (I_Kr). Here, we investigated the effect of ACh on the action potential parameters in human ventricular preparations and on I_Kr in human induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs). Using standard microelectrode technique, we demonstrated that ACh (5 µM) significantly increased the action potential duration in human left ventricular myocardial slices. ACh (5 µM) also prolonged repolarization in a human Purkinje fiber and a papillary muscle. Optical mapping revealed that ACh increased the action potential duration in human left ventricular myocardial slices and that the effect was dose-dependent. Perforated patch clamp experiments demonstrated action potential prolongation and a significant decrease in I_Kr by ACh (5 µM) in hiPSC-CMs. Computer simulations of the electrical activity of a human ventricular cardiomyocyte showed an increase in action potential duration upon implementation of the experimentally observed ACh-induced changes in the fully activated conductance and steady-state activation of I_Kr. Our findings support the hypothesis that ACh can influence the repolarization in human ventricular cardiomyocytes by at least changes in I_Kr.

Color vision testing is often considered a resource-intensive examination, requiring an anomaloscope, or at least color plates and specialized lighting equipment. Multiple novel, digital color vision testing algorithms have also been described, but were only verified using calibrated displays. In this work, we assessed if color vision testing could be performed with any computer display using two arrangement type color vision tests, the D15 and desaturated D15 panels. Established mathematical models of human color vision deficiencies (CVDs) and publicly available colorimetric data of real world computer screens were used to model how the panel colors would be displayed on computer screens and then perceived and arranged by subjects with varying levels of CVD. A total of 627,431 arrangements were evaluated. We found that all of the modeled displays, including ones with a low color accuracy of deltaE=6, were characterized by specificity above 86%, and the sensitivity of the desaturated D15 panel remained above 85% as well, with negative predictive values above 90% to detect any form of CVD compared to using the unmodifed colors. These findings suggest that any digital screen could be utilized for color vision screening, even without calibration, enabling reliable high-throughput screening utilizing equipment that is already present at virtually all healthcare providers. Since 8% of the population is affected by some form of CVD, simplifeid screening would unlock notable benefits for all stakeholders. Furthermore, the described algorithm could also be used to optimize other digital color vision tests for general use.