Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation.

It has long been thought that there is a close association between hypertension and atrial fibrillation (AF). However, the efficacy of an angiotensin II receptor blocker for the prevention of organ damage in hypertensive individuals with AF is still controversial. The present study was a multicentered, prospective, randomized, open-label clinical trial investigating the differences in the effect of treatment with telmisartan/amlodipine combination tablets on blood pressure (BP) levels and BP variability between morning and bedtime administration in hypertensive patients with paroxysmal AF, using ambulatory BP monitoring (ABPM) and home BP. With this treatment, the patients' 24-hour BP, nighttime BP, preawake BP, and morning BP shown by ABPM were significantly reduced, and the antihypertensive effects were similar regardless of the timing of the drug administration. The standard deviation of day-by-day home systolic BP and the maximum home systolic BP were also significantly reduced, and these effects were similar regardless of the treatment timing. The N-terminal pro-brain natriuretic peptide level was significantly decreased only in the bedtime administration group. A larger study will demonstrate whether the bedtime administration of telmisartan/amlodipine combination tablets maximizes the risk-lowering effect against AF recurrence in paroxysmal AF hypertensive patients.

Ghrelin counteracts salt-induced hypertension via promoting diuresis and renal nitric oxide production in Dahl rats.

Ghrelin is the endogenous ligand for the growth hormone-secretagogue receptor expressed in various tissues including the heart, blood vessels and kidney. This study sought to determine the effects of long-term treatment with ghrelin (10 nmol/kg, twice a day, intraperitoneally) on the hypertension induced by high salt (8.0% NaCl) diet in Dahl salt-sensitive hypertensive (DS) rats. Systolic blood pressure (SBP) was measured by a tail cuff method. During the treatment period for 3 weeks, high salt diet increased blood pressure compared to normal salt (0.3% NaCl) diet, and this hypertension was partly but significantly (P<0.01) attenuated by simultaneous treatment with ghrelin. Ghrelin significantly increased urine volume and tended to increase urine Na⁺ excretion. Furthermore, ghrelin increased urine nitric oxide (NO) excretion and tended to increase renal neuronal nitric oxide synthase (nNOS) mRNA expression. Ghrelin did not alter the plasma angiotensin II level and renin activity, nor urine catecholamine levels. Furthermore, ghrelin prevented the high salt-induced increases in heart thickness and plasma ANP mRNA expression. These results demonstrate that long-term ghrelin treatment counteracts salt-induced hypertension in DS rats primarily through diuretic action associated with increased renal NO production, thereby exerting cardio-protective effects.

Eye-tracking analysis of skilled performance in clinical extracorporeal circulation.

The manipulation of extracorporeal circulation (ECC), which is performed by perfusionists during cardiovascular surgery, is a highly sophisticated cognitive process based on visual information obtained from information sources such as ECC indicators, surgeons, an operating field, a scrub nurse, surgical instruments, displays, patients, among others. An eye-tracking approach is expected to be a powerful means of automatic and rapid analysis. This paper presents the results of a pilot study in which an eye-tracking approach was applied to the analysis of ECC operation tasks conducted during real clinical cardiovascular surgery in the operating room. Eye-tracking data on four perfusionists were recorded while they were manipulating the ECC during a series of cardiovascular surgeries. The experience of the perfusionists ranged from 2 to 26+ years. Based on the data obtained, fixation-by-fixation cataloging of eye-tracking data in which each fixation was transcribed in timeline style was performed for each perfusionist. Gaze allocation tendencies during the surgeries for all four perfusionists were determined through a comparative analysis. It was noted that an expert engineer dispersed his attention more widely than did intermediate and novice perfusionists. Taking the results of the data analysis into consideration, we discuss the implications of well-skilled perfusionists' performance during the manipulation of ECC, as well as the principles that guide how eye-tracking data obtained in real surgery should be processed. This is the first study on the application of an eye-tracking approach to the analysis of ECC operation tasks to be reported in the Japanese literature.

Roles of ghrelin in left-ventricular remodelling after acute myocardial infarction.

OBJECTIVE: The purpose of this study was to elucidate the role of ghrelin after acute myocardial infarction (AMI) in left ventricular (LV) remodelling. DESIGN: Prospective observational study. SETTING: Jichi Medical University Hospital. PATIENTS: Fifty consecutive patients experiencing their first AMI. INTERVENTIONS: Ghrelin was measured on the day of admission, day 7, day 14 and 6 months after AMI. Patients were treated by percutaneous coronary intervention, and successful myocardial reperfusion was accomplished within 12 h after onset. To analyse LV remodelling, the authors performed left ventriculographies on the day of admission and 6 months after AMI. MAIN OUTCOME MEASURES: Changes in LV volume. RESULTS: Plasma ghrelin increased significantly after AMI (admission: 40.9±7.3; day 7: 89.5±11.0; day 14: 92.6±11.8 fmol/ml, p<0.0001). There was a significant correlation between ghrelin on day 14 and changes in LV volume over 6 months (r=+0.46, p<0.001). Multivariate regression analysis showed that ghrelin on day 14 is a significant predictor of LV remodelling after AMI (ß=+0.44, p=0.001). CONCLUSION: To our knowledge, this is the first report that shows a relation between circulating ghrelin after AMI and the progression of LV remodelling in the chronic phase. The elevation of ghrelin after AMI might be a compensatory mechanism to attenuate LV remodelling.

Circulating endothelial progenitor cells in congestive heart failure.

BACKGROUND: Endothelial progenitor cells (EPCs) circulate in the adult peripheral blood and contribute to neovascularization. EPCs are considered to be included in CD34 positive mononuclear cells (CD34+ MNCs). Kinetics of circulating EPCs in congestive heart failure (CHF) has not been fully investigated. METHODS: We determined the numbers of white blood cells (WBCs), plasma brain natriuretic peptide (BNP), serum erythropoietin, vascular endothelial growth factor (VEGF) and thrombomodulin levels in 16 mild CHF patients (NYHA I, II), 10 severe CHF patients with acute exacerbation (NYHA III, IV), and 22 control subjects. The number of CD34+ MNCs in peripheral blood was quantified by flow cytometry. RESULTS: The ratio of CD34+ MNCs:10(3) WBCs in mild CHF patients was higher than that in control subjects (P<0.05). Interestingly, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients at admission was significantly lower than that in control subjects (P<0.005) or in mild CHF patients (P<0.05). Levels of BNP and erythropoietin in severe CHF patients were significantly higher than those in mild CHF patients. However, VEGF and thrombomodulin levels were not different between mild and severe CHF patients. In addition, the ratio of CD34+ MNCs:10(3) WBCs in severe CHF patients increased in proportion to the amelioration of CHF during hospitalization, and this increase correlated with the decrease in BNP level. CONCLUSIONS: The ratio of CD34+ MNCs:10(3) WBCs was decreased in severe CHF. These findings suggest that impaired EPC recruitment might be involved in the pathophysiology of severe CHF.

Nucleotide sequence and embryonic expression of quail and duck Sox9 genes.

Sox9 is a member of the Sry-type HMG-box (Sox) gene family. It encodes a transcription factor and is thought to be important for sexual differentiation in chicken. In the present study we have isolated Sox9 cDNAs from quail and duck, and examined the expression patterns of the corresponding genes in early embryonic gonads by whole-mount in situ hybridization. We developed a polymerase chain reaction-based protocol to identify the sex of quail and duck embryos before its morphological manifestation. Sox9 expression was first detected on days 5 and 7 in the gonads of male quail and duck embryos, respectively, and was not apparent in female gonads at these stages. These expression patterns are similar to that of chicken Sox9. Our results thus suggest that the expression of quail and duck Sox9 is associated with testis differentiation.

An anti-ulcer drug, geranylgeranylacetone, suppresses inducible nitric oxide synthase in cultured vascular smooth muscle cells.

OBJECTIVE: Geranylgeranylacetone (GGA) is commonly used as an anti-ulcer drug. If GGA affects inducible nitric oxide synthase (iNOS) in the vascular tissue, it could influence disease progression in coronary arteries. We investigated the effects of the anti-ulcer drug GGA on iNOS activity in vascular smooth muscle cells. METHODS: We measured the production of nitrite, a stable metabolite of nitric oxide, in cultured rat vascular smooth muscle cells with the Griess reagent. iNOS protein and mRNA expressions were assayed by western blotting and northern blotting, respectively. The levels of nuclear factor (NF)-kappaB proteins in nuclear extracts were analyzed by gel retardation assay. Heat shock protein 70, a cytoprotective molecule, was evaluated by western blotting. RESULTS: Incubation of cultures with interleukin-1beta for 24 h caused a significant increase in nitrite generation. Interleukin-1beta-induced nitrite production by vascular smooth muscle cells was significantly suppressed by GGA in a dose-dependent manner. GGA-suppressed nitrite production was accompanied by decreased iNOS mRNA and protein accumulations. GGA by itself did not modulate the basal level of nitrite production. Interleukin-1beta induced NF-kappaB activation in vascular smooth muscle cells, and the addition of GGA further inhibited this NF-kappaB activation. GGA itself induced heat shock protein 70 expression in a dose-dependent manner. CONCLUSION: These findings demonstrated that GGA suppresses iNOS expression in cytokine-stimulated cultured vascular smooth muscle cells partially through the suppression of NF-kappaB activation, suggesting that GGA may modulate the pathophysiology of cardiovascular diseases including atherosclerosis. In addition, this effect may be associated with heat shock protein 70 production by GGA.