It has been documented that reactive oxygen species (ROS) contribute to oxidative stress, leading to diseases such as ischemic heart disease. Recently, increasing evidence has indicated that short-term intermittent hypoxia (IH), similar to ischemia preconditioning, could yield cardioprotection. However, the underlying mechanism for the IH-induced cardioprotective effect remains unclear. The aim of this study was to determine whether IH exposure can enhance antioxidant capacity, which contributes to cardioprotection against oxidative stress and ischemia/reperfusion (I/R) injury in cardiomyocytes. Primary rat neonatal cardiomyocytes were cultured in IH condition with an oscillating O₂ concentration between 20% and 5% every 30 min. An MTT assay was conducted to examine the cell viability. Annexin V-FITC and SYTOX green fluorescent intensity and caspase 3 activity were detected to analyze the cell death. Fluorescent images for DCFDA, Fura-2, Rhod-2, and TMRM were acquired to analyze the ROS, cytosol Ca²⁺, mitochondrial Ca²⁺, and mitochondrial membrane potential, respectively. RT-PCR, immunocytofluorescence staining, and antioxidant activity assay were conducted to detect the expression of antioxidant enzymes. Our results show that IH induced slight increases of O₂^−· and protected cardiomyocytes against H₂O₂- and I/R-induced cell death. Moreover, H₂O₂-induced Ca²⁺ imbalance and mitochondrial membrane depolarization were attenuated by IH, which also reduced the I/R-induced Ca²⁺ overload. Furthermore, treatment with IH increased the expression of Cu/Zn SOD and Mn SOD, the total antioxidant capacity, and the activity of catalase. Blockade of the IH-increased ROS production abolished the protective effects of IH on the Ca²⁺ homeostasis and antioxidant defense capacity. Taken together, our findings suggest that IH protected the cardiomyocytes against H₂O₂- and I/R-induced oxidative stress and cell death through maintaining Ca²⁺ homeostasis as well as the mitochondrial membrane potential, and upregulation of antioxidant enzymes.

Cardiac autonomic neuropathy (CAN) is a common complication of diabetes mellitus, and can be assessed using heart rate variability (HRV) and the correlations between systolic blood pressure (SBP) and ECG R-R intervals (RRIs), namely baroreflex sensitivity (BRS). In this study, we propose a novel parameter for the nonlinear association between SBP and RRIs based on multiscale cross-approximate entropy (MS-CXApEn). Sixteen male adult Wistar Kyoto rats were equally divided into two groups: streptozotocin-induced diabetes and age-matched controls. RRIs and SBP were acquired in control rats and the diabetic rats at the onset of hyperglycemia and insulin-treated euglycemia to determine HRV by the ratio of low-frequency to high-frequency power (LF/HF) and Poincaré plot as SSR (SD1/SD2), BRS, and MS-CXApEn. SSR and BRS were not significantly different among the three groups. The LF/HF was significantly higher in the hyperglycemic diabetics than those in the controls and euglycemic diabetic rats. MS-CXApEn was higher in the diabetic hyperglycemic rats than the control rats from scales 2 to 10, and approached the values of controls in diabetic euglycemic rats at scales 9 and 10. Conclusions: We propose MS-CXApEn as a novel parameter to quantify the dynamic nonlinear interactions between SBP and RRIs that reveals more apparent changes in early diabetic rats. Furthermore, changes in this parameter were related to correction of hyperglycemia and could be useful for detecting and assessing CAN in early diabetes.

Background: Systematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination.Objective: To investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet.Design: A one-arm pilot intervention study.Participants/Setting: Nine patients with dyslipidemia participated in this 12-week vegan program.Main Outcome Measures: Nuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors.Statistical Analyses Performed: Wilcoxon signed-rank test.Results: In this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: −23 μmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median −24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median −75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (−23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (−0.7 kg/m², p = 0.03), waist circumferences (−2.0 cm, p < 0.001), HbA1c (−0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (−0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status.Conclusions: A dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Background: Cardiac autonomic neuropathy (CAN) is a common yet frequently underdiagnosed complication of diabetes. While our previous study demonstrated the utility of multiscale cross-approximate entropy (MS-CXApEn) in detecting early CAN, the present study further investigates the use of frequency-domain coherence analysis between systolic blood pressure (SBP) and R-R intervals (RRI) and evaluates the effects of insulin treatment on autonomic function in diabetic rats. Methods: At the onset of diabetes induced by streptozotocin (STZ), rats were assessed for cardiovascular autonomic function both before and after insulin treatment. Spectral and coherence analyses were performed to evaluate baroreflex function and autonomic regulation. Parameters assessed included low-frequency power (LFP) and high-frequency power (HFP) of heart rate variability, coherence between SBP and RRI at low and high-frequency bands (LF_Coh and HF_Coh), spontaneous and phenylephrine-induced baroreflex sensitivity (BRS_spn and BRS_phe), HRV components derived from fast Fourier transform, and MS-CXApEn at multiple scales. Results: Compared to normal controls (LF_Coh: 0.14 ± 0.07, HF_Coh: 0.19 ± 0.06), early diabetic rats exhibited a significant reduction in both LF_Coh (0.08 ± 0.04, p < 0.05) and HF_Coh (0.16 ± 0.10, p > 0.05), indicating impaired autonomic modulation. Insulin treatment led to a recovery of LF_Coh (0.11 ± 0.04) and HF_Coh (0.24 ± 0.12), though differences remained statistically insignificant (p > 0.05 vs. normal). Additionally, low-frequency LFP increased at the onset of diabetes and decreased after insulin therapy in most rats significantly, while MS-CXApEn at all scale levels increased in the early diabetic rats, and MS-CXApEn_large declined following hyperglycemia correction. The BRS_spn and BRS_phe showed no consistent trend. Conclusions: Coherence analysis provides valuable insights into autonomic dysfunction in early diabetes. The significant reduction in LF_Coh in early diabetes supports its role as a potential marker for CAN. Although insulin treatment partially improved coherence, the lack of full recovery suggests persistent autonomic impairment despite glycemic correction. These findings underscore the importance of early detection and long-term management strategies for diabetic CAN.

The prevalence and incidence of non-valvular atrial fibrillation (NVAF) in Taiwan increase with age. Low adherence to oral anticoagulants heightens stroke risk. This study evaluated whether advanced educational intervention could enhance dabigatran adherence in Taiwanese patients with NVAF. This multicenter clinical trial in Taiwan enrolled 873 patients aged 20-74 years and newly diagnosed with NVAF. Patients were randomized to receive advanced educational intervention or standard care only. Dabigatran adherence at 12 months was evaluated using the Morisky Medication Adherence Scale (MMAS-8), along with the proportion of subjects reporting "never/rarely forgetting to take dabigatran" at 3, 6, and 9 months, dabigatran discontinuation rate, and the safety outcomes in both groups. Both groups reached the maximum MMAS-8 median score at all visits, showing no significant differences. Adverse event rates were 3.9 % (17/441) in the standard care group, including four stroke and thromboembolic events, versus 4.2 % (18/432) in the advanced educational intervention group, with one stroke and thromboembolic event. Subgroup analysis of patients with initial MMAS-8 scores below 8 points showed a significant difference at sixth month (6 vs. 7, P = 0.011). Over 3, 6, 9, and 12 months, MMAS-8 scores improved in both groups, with the advanced educational intervention group achieving a perfect adherence by 12 months (routine group: 6, 6, 7, 7; advanced group: 6, 7, 7, 8). Advanced educational intervention significantly improved dabigatran adherence in younger patients with low initial adherence, demonstrating its potential in managing NVAF in Taiwan. NCT04532528.