Association between postoperative delirium and heart rate variability in the intensive care unit and readmissions and mortality in elderly patients with cardiovascular surgery.

This study aimed to investigate the relationship between heart rate variability (HRV), a parameter of the autonomic nervous system activity (ANSA), and postoperative delirium and postoperative events. This retrospective cohort study included elderly patients aged 65 years or older who were admitted to the intensive care unit (ICU) after cardiovascular surgery. ANSA was measured using HRV parameters for 1 h at daytime and 1 h at night-time before ICU discharge. The primary endpoint was the effect of HRV parameters and delirium on mortality and readmission rates within 1 year after discharge, and the secondary endpoint was the association between HRV parameters and delirium. Cox proportional hazards models were used to examine the association between HRV parameters and postoperative events by adjusting for delirium and pre and postoperative information. A total of 71 patients, 39 without delirium and 32 with delirium, met the inclusion criteria. The incidence of death and readmission within 1 year was significantly higher in the delirium group and in the group with higher daytime HF (high frequency power) and r-MSSD (square root of the squared mean of the difference of successive NN intervals), parameters of the parasympathetic nervous system activity (PNSA), than that in other groups. Furthermore, the delirium group had significantly higher HF and r-MSSD than the nondelirium group. Even after adjusting for confounding factors in the multivariate analysis, a trend of higher daytime HF and r-MSSD was observed, indicating a significant effect on the occurrence of combined events within 1 year of discharge. ICU delirium has been associated with higher daytime HF and r-MSSD, parameters of PNSA. ICU delirium was a prognostic factor, and increased daytime PNSA may worsen the prognosis of elderly patients after cardiovascular surgery.

Clinical Perspectives on Cardiac Rehabilitation After Heart Failure in Elderly Patients with Frailty: A Narrative Review.

The purpose of this narrative review is to examine rehabilitation modalities for patients with heart failure and Frailty who require comprehensive intervention. Ischemic heart disease is the leading cause of death worldwide, accounting for 16% of global mortality. Due to population growing and aging, the total number of heart failure patients continues to rise, a condition known as the heart failure pandemic. Furthermore, frailty has been associated with an increased risk for heart failure and increased morbidity and mortality. The 2021 update of the 2017 ACC expert consensus decision pathway for optimization of HF treatment has become more concerning, citing frailty as one of the 10 most important issues associated with heart failure with reduced ejection fraction (HFrEF). Frailty and heart failure share common pathological mechanisms and are associated with poor clinical outcomes. Most studies of frailty in patients with heart failure primarily focus on physical frailty, and associations between psycho-psychological and social factors such as cognitive dysfunction and social isolation have also been reported. These results suggest that a more comprehensive assessment of frailty is important to determine the risk in patients with heart failure. Therefore, mechanisms of the three domains, including not only physical frailty but also cognitive, psychological, spiritual, and social aspects, should be understood. In addition to interventions in these three domains, nutritional and pharmacological interventions are also important and require tailor-made interventions for the widely varied conditions associated with heart failure and frailty. Although several studies have shown a relationship between frailty and prognosis in patients with heart failure, interventions to improve the prognosis have not yet been established. Further information is needed on frailty intervention by a multidisciplinary team to improve the prognosis.

Antidiabetic effect of enterolactone in cultured muscle cells and in type 2 diabetic model db/db mice.

Enterolactone (ENL) is formed by the conversion of dietary precursors like strawberry lignans via the gut microbiota. Urinary concentrations of lignan metabolites are reported to be significantly associated with a lower risk of Type 2 diabetes (T2D). In the present study, antidiabetic effect of ENL and its modes of action were studied in vitro and in vivo employing a rat skeletal muscle-derived cell line, L6 myocytes in culture, and T2D model db/db mice. ENL dose-dependently increased glucose uptake in L6 myotubes under insulin absent condition. This increase by ENL was canceled by compound C, an inhibitor of 5'-adenosine monophosphate-activated protein kinase (APMK). Activation (=phosphorylation) of AMPK and translocation of glucose transporter 4 (GLUT4) to plasma membrane in L6 myotubes were demonstrated by Western blotting analyses. Promotion by ENL of GLUT4 translocation to plasma membrane was also visually demonstrated by immunocytochemistry in L6 myoblasts that were transfected with glut4 cDNA-coding vector. T2D model db/db mice were fed the basal 20 % casein diet (20C) or 20C supplemented with ENL (0.001 or 0.01 %) for 6 weeks. Fasting blood glucose (FBG) levels were measured every week and intraperitoneal glucose tolerance test (IPGTT) was conducted. ENL at a higher dose (0.01 % in 20C) suppressed the increases in FBG levels. ENL was also demonstrated to improve the index of insulin resistance (HOMA-IR) and glucose intolerance by IPGTT in db/db mice. From these results, ENL is suggested to be an antidiabetic chemical entity converted from dietary lignans by gut microbiota.

Antihyperglycemic effect of equol, a daidzein derivative, in cultured L6 myocytes and ob/ob mice.

SCOPE: Molecular mechanisms for the potential antihyperglycemic effect of equol remain to be elucidated. In this study, we investigated the in vitro effect of equol on glucose uptake, AMP-activated protein kinase (AMPK) phosphorylation, and glucose transporter 4 (GLUT4) translocation to plasma membrane in L6 myocytes, and its in vivo antihyperglycemic effect in obese-diabetic model ob/ob mice. METHODS AND RESULTS: Equol was found to promote glucose uptake, AMPK phosphorylation, and GLUT4 translocation detected by Western blotting analyses in L6 myotubes under a condition of insulin absence. Equol (0.05% in diet) suppressed the rise in serum glucose, cholesterol, triglyceride, and lipid peroxide concentrations and the hepatic triglyceride level as compared with those in the control group. Moreover, equol treatment suppressed the rises in fasting blood glucose level and improved the impaired glucose tolerance in ob/ob mice. Furthermore, equol treatment was demonstrated to improve expression of hepatic gluconeogenesis- and lipogenesis-related genes in terms of glucose and lipid metabolism. CONCLUSION: The hypoglycemic effect of equol is related to increased GLUT4 translocation to the plasma membrane via AMPK activation. In addition, equol suppresses the fasting blood glucose level and gene expression of hepatic enzymes related to glucose metabolism. These results strongly suggest that equol has antidiabetic potential.

Daidzein promotes glucose uptake through glucose transporter 4 translocation to plasma membrane in L6 myocytes and improves glucose homeostasis in Type 2 diabetic model mice.

Daidzein shows estrogenic, antioxidant and antiandrogenic properties as well as cell cycle regulatory activity. However, the antihyperglycemic effect of daidzein remains to be elucidated. In this study, we investigated the in vitro effect of daidzein on glucose uptake, AMPK phosphorylation and GLUT4 translocation on plasma membrane in L6 myotubes and its in vivo antihyperglycmic effect in obese-diabetic model db/db mice. Daidzein was found to promote glucose uptake, AMPK phosphorylation and GLUT4 translocation by Western blotting analyses in L6 myotubes under a condition of insulin absence. Promotion by daidzein of glucose uptake as well as GLUT4 translocation to plasma membrane by immunocytochemistry was also demonstrated in L6 myoblasts transfected with a GLUT4 cDNA-coding vector. Daidzein (0.1% in the diet) suppressed the rises in the fasting blood glucose, serum total cholesterol levels and homeostasis model assessment index of db/db mice. In addition, daidzein supplementation markedly improved the AMPK phosphorylation in gastrocnemius muscle of db/db mice. Daidzein also suppressed increases in blood glucose levels and urinary glucose excretion in KK-Ay mice, another Type 2 diabetic animal model. These in vitro and in vivo findings suggest that daidzein is preventive for Type 2 diabetes and an antidiabetic phytochemical.