Manabu Kokubo

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

The spontaneously hypertensive rat (SHR) has been well established as a suitable model for studies of hypertension, but little is known about the processes of left ventricular (LV) hypertrophy and the changes in cardiac function in this model. The present study was designed to provide a noninvasive evaluation of the time-dependent alteration of cardiac function in male SHR at 4 to 24 weeks of age and age-matched Wistar-Kyoto rats (WKY). Echocardiographic studies were performed after blood pressure (BP) and heart rate (HR) were measured by a tail-cuff method. The body weight (BW) of SHR was lighter than that of WKY at all ages, and HR was consistently lower, with significantly elevated systolic BP from 4 weeks of age. In the echocardiographic study, LV mass at 4 weeks of age was similar between WKY and SHR, although the ratio of LV mass to BW was higher in SHR than WKY. The ejection fraction, fractional shortening (FS) and midwall FS did not differ between the two groups at 4 weeks, but after 8 weeks, these parameters were decreased in the SHR. The deceleration time was prolonged in SHR after 16 weeks and the E/A ratio was lowered at 12 weeks. We also analyzed the expression levels of calcineurin, which were found to be increased in both groups with age. These results suggest that calcineurin does not play a major role in the development of LV hypertrophy. Thus, in SHR, cardiac hypertrophy develops by 4 weeks of age, and systolic and diastolic dysfunction is evident at 2 to 3 months.

Impact of night-time blood pressure on cerebral white matter hyperintensity in elderly hypertensive patients.

Cerebral white matter hyperintensity (WMH) is highly prevalent in the elderly population, and increases the risk of dementia and stroke. We investigated the relationship between ambulatory blood pressure monitoring levels and quantitatively measured WMH volumes among elderly hypertensive patients with well‐controlled blood pressure (BP) to re‐evaluated effective hypertension management methods to prevent the progression of WMH.

A giant pseudoaneurysm of the sinus of Valsalva with pulmonary artery obstruction

Figure 2: An aortogram revealed a giant aneurysm (arrow heads) arising from the aortic root. There was extremely slow contrast filling and washout of the giant aneurysm (A and B). A right ventricular angiogram demonstrated obstruction at the main pulmonary artery (C). Emergent surgery was performed because of the patient’s severe condition. After opening the pericardium, a giant aneurysm with dark violet irregular surface became visible (D). The aneurysm was incised and the sinus of Valsalva was repaired by the Yacoub procedure. The post-operative course was uneventful. A, aneurysm; RV, right ventricle.

Left ventricular diastolic dysfunction is directly associated with cerebral white matter lesions in elderly patients.

Cerebral white matter lesions (WML) have been established to increase with age, and are associated with heightened risks of stroke, cognitive decline and depressive disorder. We previously reported that the severity of left ventricular (LV) diastolic dysfunction is associated with the volume of cerebral WML. However, the analysis could not be carried out by removing the effect of the common or specific risk factors that are known to be involved in the progression of LV diastolic dysfunction and/or cerebral WML, such as age, hypertension, diabetes mellitus, hyperlipidemia, smoking, obesity and so on. Consequently, whether LV diastolic dysfunction is directly associated with cerebral WML remained unclear. Therefore, to clarify this, we carried out a cross-sectional study by conducting further in-depth examination of these risk factors and also by increasing the study population. The study registration period was from April 2010 to October 2013. Participants comprised 133 outpatients between aged 65 and 75 years with normal LV contraction (ejection fraction >50%) and no signs or history of symptomatic heart failure, ischemic heart diseases, atrial fibrillation, stroke, or cognitive dysfunction. We also excluded those patients with ≥50% stenosis in the carotid arteries on ultrasonography with 2-D and Doppler analysis. The volume of cerebral WML was quantified on brain magnetic resonance imaging using a fully automatic segmentation program developed in the Department of Radiology at Leiden University Medical Center (Leiden, the Netherlands), and early diastolic mitral inflow and early diastolic mitral annular tissue velocity (E/E’) ratio, a parameter that indicates the severity of LV diastolic dysfunction, was measured by tissue Doppler echocardiography. A total of 20 4-h systolic and diastolic blood pressure were obtained by ambulatory blood pressure monitoring. In addition, LV ejection fraction, body mass index, estimated glomerular filtration rate, carotid intimal media thickness, and levels of plasma B-type natriuretic peptide, hemoglobin A1c and low density lipoprotein cholesterol were also determined. Values are shown as mean ± standard deviation unless otherwise stated. Data were analyzed using SPSS version 17.0 software (SPSS, Chicago, IL, USA). The study protocol was approved by the ethics/conflict of interest committee at the National Center for Geriatrics and Gerontology. Written informed consent was obtained from all participants before participation. Table A shows the patient characteristics. The results of linear regression analysis between cerebral WML volume and estimated factors are shown in Table B. These results showed that four factors (age, systolic blood pressure, plasma B-type natriuretic peptide and E/E’) had a significant correlation (P < 0.05) with cerebral WML volume. Based on the results, multivariate analysis was carried out in order to clarify the principal factors involved in the increase of the cerebral WML. As a result, E/E’ and age had been shown to be significantly correlated with cerebral WML volume (P < 0.01), with the correlation greater for E/E’ (P = 0.003) than for age (P = 0.03; Table C). The present study clarified the direct association between the severity of LV diastolic dysfunction and the volume of WML in elderly patients even after removing the effects of risk factors that were involved in the progression of LV diastolic dysfunction and/or cerebral WML. The results can be interpreted in two ways. The first interpretation is that a common, but unknown, factor exacerbates both cerebral WML and LV diastolic dysfunction, with this complicating factor being profoundly involved in the onset and progression of both diseases. The second interpretation involves chronic low cardiac output and chronic cerebral ischemia. Some reports in recent years have suggested that cerebral perfusion is impaired in patients with chronic low cardiac output. Thus, considering that cardiac output decreases with the decrease in blood flow into the LV from the left atrium as a result of the progression in LV diastolic dysfunction, and also considering that a chronic decrease in cerebral blood flow is thought to be the primary mechanism underlying cerebral WML formation, the present results can also be interpreted as suggesting that decreased cardiac output elicits chronic cerebral ischemia. Further investigation is necessary to clarify these points. Correspondence: Dr. Manabu Kokubo MD PhD, Department of Cardiology, National Center for Geriatrics and Gerontology, 7-430, Morioka-cho, Obu, Aichi 474-8511, Japan. Email: mkokubo@ncgg.go.jp Geriatr Gerontol Int 2015; 15 (Suppl. 1): 81–85 bs_bs_banner