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Oxidative stress under pathological conditions, such as ischemia/reperfusion and inflammation, results in the production of various reactive chemicals. Of these chemicals, 4-hydroxynonenal (4-HNE), a peroxidation product of ω6-polyunsaturated fatty acid, has garnered significant attention. However, the effect of 4-HNE on cardiac electrophysiology has not yet been reported. In the present study, we investigated the effects of 4-HNE on several cardiac ion channels, including human ether-a-go-go-related (hERG) channels, using the whole-cell patch clamp technique. Short-term exposure to 100 μM 4-HNE (4-HNE100S), which mimics local levels under oxidative stress, decreased the amplitudes of rapidly activating delayed rectifier K+ current (IKr) in guinea pig ventricular myocytes (GPVMs) and HEK293T cells overexpressing hERG (IhERG). MS analysis revealed the formation of 4-HNE-hERG adduct on specific amino acid residues, including C276, K595, H70, and H687. Long-term treatment (1–3 h) with 10 μM 4-HNE (4-HNE10L), suppressed IKr and IhERG, but not IKs and ICa,L. Action potential duration (APD) of GPVMs was prolonged by 37% and 64% by 4-HNE100S and 4-HNE10L, respectively. Western blot analysis using surface biotinylation revealed a reduction in mature membrane hERG protein after treatment with 4-HNE10L. Proteasomal degradation inhibitors, such as bortezomib, prevented the 4-HNE10L-induced decrease in mature hERG, suggesting a retrograde degradation of membrane hERG due to 4-HNE. Taken together, 4-HNE100S and 4-HNE10L suppressed IhERG via functional inhibition and downregulation of membrane expression of hERG, respectively. The exposure of 4-HNE under pathological oxidative stress may increase the risk of proarrhythmic events via APD prolongation. Keywords: Lipid peroxidant, 4-hydroxynonenal, hERG channel, Cardiac action potential prolongation

Background and Objective: Hypertension is critical risk factor of fatal cardiovascular diseases and multiple organ damage. Early detection of hypertension even at pre-hypertension stage is helpful in preventing the forthcoming complications. Electrocardiogram (ECG) has been attempted to observe the changes in electrical activities of the hearts of hypertensive patients. To automate the ECG assessment in the detection of hypertension, an interpretable hybrid model is proposed in this paper. Methods: The proposed hybrid framework consists of one dimensional - Convolutional Neural Network architecture with four blocks of convolutional layers, maxpooling followed by dropout layers fused with Support Vector Machine classifier in the final layer. The implemented hybrid model is made explainable and interpretable using Local Interpretable Model-agnostic Explanations (LIME) method. The developed hybrid model is trained and tested for patient-wise classification of ECGs using online Physionet datasets and hospital data. Results: The proposed method achieved highest accuracy of 81.81% in patient-wise ECG classification of online datasets, and highest accuracy of 93.33% in patient-wise ECG classification of hospital datasets as normotensive and hypertensive. The visualization of results showed only one normotensive patient's ECG is misclassified (predicted) as hypertensive, with identification of patient number, among the 15 patients (8 normotensive and 7 hypertensive) ECGs tested. In addition, the LIME results demonstrated an explanation to the predictions of hybrid model by highlighting the features and location of ECG waveform responsible for it, thus making the decision of hybrid model more interpretable. Conclusion: Furthermore, our developed system is implemented as an assisting automated software tool called, HANDI (Hypertensive And Normotensive patient Detection with Interpretability) for real-time validation in clinics for early capture of hypertensive and proper monitoring of the patients.

Background: Neutrophil to lymphocyte ratio (NLR) in peripheral blood is established to correlate with the morbidity and mortality of heart disease patients. We aimed to define the severity of inflammation (NLR) by observing the association of NLR with cardiac functions or myocardial damage parameters in patients with acute myocardial infarction. Methods: Data from 715 patients who underwent percutaneous coronary intervention (PCI) within 72 hours of incidence in 2016 were analysed retrospectively. Results: The NLR ranges from 0.50 to 46 (medium ± SD, 2.76 ± 2.96) in 715 patients. NLR positively correlated with myocardial damage (NLR vs. CK-mB: p 2.76 compared to those of NLR 4. The correlation was diminished between NLR and CK-mB at NLR > 2.76 or at NLR > 4, but that of NLR and EF or FS was maintained in NLR > 2.76 and at NLR > 4. EF and FS were comparable between NLR > 2.76 and NLR > 4. But myocardial damage parameters increased significantly at NLR > 4 compared to those of NLR > 2.76. Conclusion: NLR is a strong predictor of myocardial damage in acute myocardial patients. High NLR are associated with myocardial dysfunction in all the patients. Severe inflammation (NLR) can predict the consequence of the heart in patients with coronary syndrome. Keywords: Neutrophil, Lymphocyte, Acute myocardial infarction, Myocardial damage, Dysfunction