Risks and predictors of mild diastolic dysfunction among middle-aged and aged women: a population-based cohort study.

We sought to determine the predictors of primary episodes of mild diastolic dysfunction (DD) in a cohort of women aged >45 years, who had >2 echocardiography from 2009 to 2012. Patients were excluded if they had prior diagnosis of coronary artery disease, heart failure, valvular heart disease or echocardiographic evidence of DD. Mild DD was defined as: left ventricular ejection fraction>50%, E/A ratio<0.75, and E/e'⩽8. Out of the total 758 subjects (age 64.15±7.24 years), 109 (14.3%) had developed mild DD, during a mean followup period of 3 years. Independent predictors of mild DD included: age (P<0.001), history of hypertension (P=0.022), body mass index (BMI) (P<0.001), total triglycerides (TG) (P=0.016), inter ventricular septal thickness (P=0.015) and brachial-ankle pulse wave velocity (baPWV) ⩾16 m s(-1) (P<0.001). E/A ratio was inversely associated with age (r=-0.337, P<0.001), baPWV (r=-0.359, P<0.001), BMI (r=-0.290, P<0.001) and TG (r=-0.255, P<0.001). The Area Under roc Curve for a linear combination of age, BMI, baPWV and TG was 0.738 (95% confidence interval: 0.683-0.804, P<0.001), which was superior to any of the variables taken alone. In summary, many middle-aged or elderly women may develop mild DD within a relatively short period of 3 years. Several subclinical abnormalities and cardiovascular parameters were determined to contribute to the onset of DD.

Modulation of cardiac interstitial noradrenaline levels through K(ATP) channels during ischemic preconditioning in rabbits: comparison of the effect of anesthesia between pentobarbital and ketamine + xylazine.

In rabbits, both the stimulation of alpha1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. One candidate for the mechanism of PC is noradrenaline (NA), which stimulates alpha1-adrenoceptors in the myocardium during PC. Opening of the K(ATP) channel is considered to be another candidate for PC, since a K(ATP) channel blocker, glibenclamide, blocks the infarct size-reducing effect of the PC of 5-min ischemia and 5-min reperfusion in rabbits anesthetized with ketamine + xylazine. However, in rabbits anesthetized with pentobarbital, the infarct size-reducing effect of PC was not blocked by glibenclamide. The effect of glibenclamide on the PC effect thus differs depending on the anesthesia used. Therefore, we speculated that the increase in cardiac interstitial NA levels induced by PC may be modified by the anesthesia used, thus regulating the effect of glibenclamide on the PC effect. In open-chest Japanese white male rabbits anesthetized with pentobarbital or ketamine + xylazine, myocardial interstitial NA levels were measured before and during the PC of 5-min ischemia and 5-min reperfusion in the presence or absence of the K(ATP) channel blocker, glibenclamide (0.3 mg/kg, i.v.), using a microdialysis technique. The NA levels were measured using high-performance liquid chromatography coupled with electrochemical detection. The PC of 5-min ischemia and 5-min reperfusion significantly elevated the interstitial NA level. This increase in the NA level was not blocked by glibenclamide under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, the PC did not cause an increase in the myocardial interstitial NA level in either the absence or the presence of glibenclamide. In conclusion, PC elevates the myocardial interstitial NA level, and this elevation is not mediated through the opening of the K(ATP) channel under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, PC does not cause an increase in the myocardial interstitial NA level. This may explain the discrepancy in the blocking effect of glibenclamide on the infarct size-reducing effect of PC between anesthesia with pentobarbital and ketamine + xylazine.