Differential impact of antihypertensive drugs on cardiovascular remodeling: a review of findings and perspectives for HFpEF prevention.

Heart failure (HF) is an important health problem worldwide whose stages have traditionally been classified from A to D. In addition, HF can be categorized as that with preserved ejection fraction (HFpEF) and that with reduced ejection fraction (HFrEF). Hypertension and arterial stiffness in stage A HF are major drivers of the progression to left ventricular hypertrophy (LVH), a criterion of stage B HF. Although the pathogenesis of HFpEF is heterogeneous, affected patients tend to be older than HFrEF patients and have a greater prevalence of hypertension, which is closely associated with arterial stiffness and LVH. Thus, to treat HFpEF, the optimal intervention for improving prognosis is an aggressive approach to early-stage, i.e., Stage A and B, HF. This paper reviews the findings on arterial stiffness and LVH using conventional antihypertensive drugs such as angiotensin receptor II blockers (ARBs) and a new drug class for HF, ARB/neprilysin inhibitor (ARNi). Previous studies have suggested that the combination of an ARB with an L-T-type calcium channel blocker might be recommended for the improvement of arterial stiffness and regression of LVH. More recent research has shown that ARNi also improves central BP, which leads to a reduced afterload and a significant reduction in LVH. For optimal treatment of HFpEF, drug therapy should directly address arterial stiffness as well as hypertension.

A Simple Electrostatic Precipitator for Trapping Virus Particles Spread via Droplet Transmission.

The purpose of this study was to develop a simple electrostatic apparatus to precipitate virus particles spread via droplet transmission, which is especially significant in the context of the recent coronavirus disease 2019 (COVID-19) pandemic. The bacteriophage φ6 of Pseudomonas syringae was used as a model of the COVID-19 virus because of its similar structure and safety in experiments. The apparatus consisted of a spiked, perforated stainless plate (S-PSP) linked to a direct-current voltage generator to supply negative charge to the spike tips and a vessel with water (G-water) linked to a ground line. The S-PSP and G-water surface were paralleled at a definite interval. Negative charge supplied to the spike tips positively polarised the G-water by electrostatic induction to form an electric field between them in which ionic wind and negative ions were generated. Bacteriophage-containing water was atomised with a nebuliser and introduced into the electric field. The mist particles were ionised by the negative ions and attracted to the opposite pole (G-water). This apparatus demonstrated a prominent ability to capture phage-containing mist particles of the same sizes as respiratory droplets and aerosols regardless of the phage concentration of the mist particles. The trapped phages were successfully sterilised using ozone bubbling. Thus, the present study provides an effective system for eliminating droplet transmission of viral pathogens from public spaces.

Body Water-Mediated Conductivity Actualizes the Insect-Control Functions of Electric Fields in Houseflies.

In the present study, the relationship between body water loss and conductivity was examined in adult houseflies (Musca domestica). The events an insect experiences in an electric field are caused by the conductive nature of the insect body (i.e., movement of electricity within or its release from the insect). After houseflies were dehydrated, rehydrated, refrigerated, and frozen and thawed, they were placed in static and dynamic electric fields. Untreated houseflies were deprived of their free electrons to become positively charged and then attracted to the insulated negative pole in the static electric field and were exposed to corona and arc discharge from non-insulated negative pole in the dynamic electric field. There was no current in the bodies of dehydrated and frozen flies; hence, there was no attractive force or discharge exposure. In the remaining insects, the results were identical to those in the untreated control insects. These results indicated that the reduction of body water conductivity inhibited the release of electricity from the body in the static electric field and the discharge-mediated current flow through the body in the dynamic electric field. The insect was affected by the electric fields because of its conductivity mediated by body water.

Effects of Olmesartan and Azilsartan on Albuminuria and the Intrarenal Renin-Angiotensin System.

PURPOSE: Olmesartan and azilsartan decrease blood pressure more effectively than other angiotensin receptor blockers (ARBs). ARBs additionally decrease the urinary albumin to creatinine ratio (UACR), a urinary albumin marker, and urinary angiotensinogen (u-AGT), an intrarenal renin-angiotensin system activity marker. We examined the effects of these ARBs on blood pressure, UACR, and u-AGT in patients with uncontrolled hypertension. METHODS: Patients with uncontrolled hypertension treated with conventional ARBs, excluding olmesartan and azilsartan, for over 8 weeks were enrolled. We randomly switched patients from their prior ARBs to either olmesartan or azilsartan, and followed them for 24 weeks. RESULTS: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and central systolic blood pressure (cSBP) significantly decreased at 24 weeks. UACR and u-AGT also decreased at 24 weeks in both groups. There were no significant differences in SBP, DBP, cSBP, UACR, or u-AGT between the groups. Therefore, we combined both groups for further analyses. After combining, SBP (160.5 ± 16.4 to 139.6 ± 15.6 mm Hg, P < 0.0001), DBP (88.4 ± 13.7 to 80.7 ± 13.2 mm Hg, P = 0.008), cSBP (167.4 ± 20.8 to 146.6 ± 24.6 mm Hg, P < 0.0001), UACR (13.8 to 9.0 mg/g Cre, P = 0.0096), and u-AGT (4.13 to 2.32 µg/g Cre, P = 0.0074) significantly decreased at 24 weeks. Patients with microalbuminuria (UACR ≥ 30 mg/g Cre) had significantly greater ΔUACR (-39.4 vs 0.27, P = 0.0024) and Δu-AGT (-11.9 vs -0.61, P = 0.0235) than patients without microalbuminuria. The changes in u-AGT were significantly associated with changes in UACR (r = 0.411, P = 0.046); however, there was no significant relationship between the changes in u-AGT and those in SBP or DBP. CONCLUSION: Olmesartan and azilsartan decreased blood pressure, UACR, and u-AGT more than the other ARBs, and exerted depressor and renoprotective effects.

Comparison between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers on the risk of stroke recurrence and longitudinal progression of white matter lesions and silent brain infarcts on MRI (CEREBRAL study): rationale, design, and methodology.

OBJECTIVES: Patients with a history of ischemic stroke are known to develop new ischemic stroke. While asymptomatic, the presence and progression of silent brain infarcts and white matter lesions on magnetic resonance imaging are associated with an increased risk of future strokes. Both angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are recommended for the primary and secondary prevention of stroke, but there are no direct comparisons of angiotensin-converting enzyme inhibitors versus angiotensin II receptor blockers regarding their cerebroprotective effects, including their effect on asymptomatic cerebral lesions detected by magnetic resonance imaging. METHODS: Elderly (65 years or older) patients with essential hypertension who underwent cerebral magnetic resonance imaging and were found to have any cerebral ischemic lesions, such as cerebral infarction, silent brain infarct, or white matter lesion, were enrolled in this CEREBRAL study. Patients who agreed to participate were enrolled in the randomized controlled trial portion. Patients who did not agree to participate in the randomized controlled trial were enrolled in the cohort study portion. After two-years of angiotensin-converting enzyme inhibitor or angiotensin II receptor blockers treatment, follow-up magnetic resonance imaging examination will be performed. The primary end-point is the composite of (1) occurrence of a fatal or nonfatal cerebrovascular event or (2) progression of cerebrovascular lesions as evaluated by magnetic resonance imaging, including white matter lesions or silent brain infarcts. After enrollment, cognitive function was evaluated, if possible, using the Mini-Mental State Examination. CONCLUSIONS: Our study will clarify whether angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers are more effective for preventing primary and recurrence of ischemic stroke, including the progression of asymptomatic cerebral lesions on magnetic resonance imaging, in elderly hypertensive patients.

Difference in cerebral and peripheral hemodynamics among term and preterm infants during the first three days of life.

BACKGROUND: The relationship between cerebral and peripheral hemodynamics during the early postnatal period has not been clarified. OBJECTIVES: To evaluate cerebral and peripheral oxygenation and blood volumes between term and preterm infants during the first 3 days of life. MATERIALS AND METHODS: We performed near-infrared time-resolved spectroscopy on 32 term infants (term group) and 40 preterm infants (preterm group), with an optode placed on their forehead and upper arm. The cerebral blood volume (CBV), peripheral blood volume (PBV), cerebral Hb oxygen saturation (cSO2) and peripheral Hb oxygen saturation (pSO2) were measured at 3-6, 12, 24, 48 and 72 h after birth. RESULTS: The CBV in the term group (2.45 ± 0.47 ml/100 g) was significantly higher than that in the preterm group (1.97 ± 0.33 ml/100 g). In contrast to the CBV, the PBV in the preterm group (3.63 ± 0.76 ml/100 g) was significantly higher than that in the term group (3.26 ± 0.56 ml/100 g). In the preterm group, there was a significant positive relationship between the CBVs and PBVs at each time point except at 72 h after birth. Despite the differences in blood volumes, there were no differences in the cSO2 and pSO2 between the two groups. CONCLUSIONS: The contrasting results in the CBV and PBV between the term and preterm infants might be explained by differences in the maturation of the physiological mechanism to control CBV and PBV.

Comparison of changes in cerebral and systemic perfusion between appropriate- and small-for-gestational-age infants during the first three days after birth.

PURPOSE: The aims of the current study were to compare changes in cerebral and systemic perfusion in appropriate-for-gestational-age (AGA) and small-for-gestational-age (SGA) infants immediately after birth. METHODS: Cerebral blood volume (CBV), cerebral Hb oxygen saturation (cSO2) and cerebral fractional tissue oxygen extraction (cFTOE) among 57 AGA infants and 30 SGA infants were monitored using a newly developed time-resolved spectroscopy system during the first 3days of life. The left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO) and E/e' values were determined by three-dimensional echocardiography and tissue Doppler imaging performed simultaneously. RESULTS: There were significant differences between the body weights of both the AGA and SGA infants, but not between the gestational age and head circumferences in both groups. Although CBV showed no significant difference between the groups, cSO2 was significantly higher and cFTOE was lower in SGA infants than in AGA infants. Hematocrit (Ht) levels were significantly higher and LVEF and LVCO were lower in SGA infants than in AGA infants. Negative correlation was observed between CBV and Ht levels in AGA infants, but not in SGA infants. CONCLUSIONS: The high Ht levels and vasoreactivity in SGA infants might be a compensatory mechanism in order to maintain oxygen delivery to the brain, which reflects the condition of chronic hypoxia during the fetal period and also reflects the weak contraction and low cardiac output of the left ventricle sustaining the relatively large brain from the fetal period to after birth.

Azelnidipine plus olmesartan versus amlodipine plus olmesartan on arterial stiffness and cardiac function in hypertensive patients: a randomized trial.

PURPOSE: To compare the long-term effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP), left ventricular (LV) mass index (LVMI), LV diastolic function (e' velocity, E/e' ratio, E/A ratio) and arterial stiffness (brachial-ankle pulse wave velocity [baPWV] and augmentation index normalized for a heart rate of 75 bpm [AIx]). PATIENTS AND METHODS: Patients with systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg/day) for 12 weeks. They were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg/day; n = 26) or amlodipine (5 mg/day; n = 26) for a further 2 years. CBP, LVMI, e' velocity, E/e' ratio, E/A ratio, baPWV, and AIx were measured at baseline, 6 months, and 2 years. RESULTS: Baseline characteristics of both groups were similar. The decrease in brachial BP over 2 years was similar in both groups. CBP, LVMI, E/e' ratio, baPWV, and AIx decreased significantly, and the E/A ratio and e' velocity increased significantly in both groups. The decreases in CBP (P < 0.001), AIx (P < 0.001), baPWV (P < 0.001), LVMI (P < 0.001), and E/e' (P = 0.002) as well as the increase in E/A ratio (P = 0.03) over 2 years were significantly greater in the olmesartan/azelnidipine group than in the olmesartan/amlodipine group. Multivariate linear regression analyses showed that the changes in baPWV (ß = 0.41, P < 0.001) and CBP (ß = 0.47, P = 0.01) were independently associated with the change in LVMI, the change in baPWV (ß = 0.25, P < 0.001) was independently associated with the change in E/e' ratio, and the changes in baPWV (ß = 0.21, P = 0.001) and AIx (ß = 0.25, P = 0.03) were independently associated with the change in E/A ratio. CONCLUSION: Treatment with olmesartan/azelnidipine for 2 years resulted in greater improvements in CBP, LVMI, and LV diastolic function, and arterial stiffness compared with olmesartan/amlodipine. Improvements in LV diastolic function were associated with improvements in arterial stiffness.

Effects of indomethacin on patent ductus arteriosus in neonates with genetic disorders and/or congenital anomalies.

OBJECTIVES: The study aimed to evaluate the effectiveness of intravenous indomethacin (IND) therapy for patent ductus arteriosus (PDA) in neonates with genetic disorders and/or congenital anomalies soon after birth. STUDY DESIGN: A total of 301 neonates with a genetic disorder and/or congenital anomalies and with a gestational age of ≥ 35 weeks were admitted during the study period. Eighty-five neonates with 56 genetic disorders (30 cases of trisomy 21, 10 cases of trisomy 18, and 16 others) and 29 congenital anomalies, and with clinical symptoms received intravenous IND therapy. The management methods were similar to those used for PDA in low-birth-weight infants. RESULTS: IND therapy had a clinical benefit at a high rate of 79% in these patients (90% and 70% in neonates with trisomies 21 and 18, respectively), including complete closure of the PDA in 52% of the patients. Although oliguria was observed in 43 infants (51%) and slight gastrointestinal bleeding was observed in 12 (14%), no infants had severe complications such as intracranial bleeding. CONCLUSIONS: IND therapy is an effective treatment option before considering surgery for PDA in neonates with genetic disorders and/or congenital anomalies. This therapy may reduce the difficulty of treatment in the acute stage among these neonates.

Adding thiazide to a rennin-angiotensin blocker regimen to improve left ventricular relaxation in diabetes and nondiabetes patients with hypertension.

The urinary albumin to creatinine ratio (UACR) is an independent predictor of outcomes in patients with diastolic dysfunction. Thus, we investigated the relationship between diastolic dysfunction, UACR, and diabetes mellitus (DM) in the EDEN study. We investigated the effect of switching from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) to a combination of losartan and hydrochlorothiazide on left ventricular (LV) relaxation in patients with hypertension and diastolic dysfunction. We enrolled 106 patients with and 265 patients without DM. All patients had diastolic dysfunction and had not achieved their treatment goals with an ACEi or ARB. The measurements of e' velocity and E/e' ratio was performed with echocardiography as markers of LV diastolic function. We switched the ACEi or ARB to losartan/hydrochlorothiazide and followed these patients for 24 weeks. UACR was decreased in patients with DM (123.4 ± 288.4 to 66.5 ± 169.2 mg/g creatinine; P = 0.0024), but not in patients without DM (51.2 ± 181.8 to 39.2 ± 247.9 mg/g creatinine; P = 0.1051). Among DM patients, there was a significant relationship between changes in UACR and changes in e' velocity (r = -0.144; P = 0.0257) and between changes in estimated glomerular filtration rate and changes in the E/e' ratio (r = -0.130; P = 0.0436). Among patients without DM, there was a significant relationship between changes in high-sensitivity C-reactive protein (hs-CRP) and changes in E/e' (r = 0.205; P = 0.0010). Multivariate analysis demonstrated changes in hemoglobin A(1c) levels as one of the determinants of change of e' and E/e' in patients with DM, whereas hs-CRP was the determinant of change of e' among patients without DM. These data suggest that improvement in LV diastolic function is associated with an improvement of DM and a concomitant reduction in UACR among DM patients, and with a reduction of hs-CRP in patients without DM when thiazide is added to a renin-angiotensin blocker treatment regimen.

Umbilical cord milking stabilizes cerebral oxygenation and perfusion in infants born before 29 weeks of gestation.

OBJECTIVE: To investigate the effects of umbilical cord milking at birth on cerebral perfusion and systemic perfusion in very low birth weight (VLBW) infants. STUDY DESIGN: Cerebral tissue oxygenation index and cerebral fractional tissue oxygen extraction were monitored in 50 stable VLBW infants (gestational age <29 weeks, birth weight <1250 g), with 26 allocated to the milked group and 24 to the control group. We used near-infrared spectroscopy 3-6, 12, 18, 24, 36, 48, and 72 hours after birth. Left ventricular end-diastolic dimension, left ventricular ejection fraction, left ventricle (LV) Tei index (measurement of left ventricular systolic and diastolic function), left ventricular cardiac output, and superior vena cava flow were measured concurrently using echocardiography. RESULTS: There were no significant differences in gestational age and birth weight between the 2 groups. Hematocrit, left ventricular end-diastolic dimension, left ventricular cardiac output, and superior vena cava flow were higher in the milked group than in the control group, with improvement in the LV Tei index despite the absence of left ventricular ejection fraction changes within 24 hours after birth. Tissue oxygenation index increased and cerebral fractional tissue oxygen extraction decreased in the milked group within 24 hours after birth. CONCLUSION: Umbilical cord milking stabilized cerebral oxygenation and perfusion in VLBW infants by improving LV diastolic function by increasing LV preload.

Major risk factors for the appearance of white-matter lesions on MRI in hypertensive patients with controlled blood pressure.

PURPOSE: Blood pressure (BP), age, and reduced renal function are major risk factors for white-matter lesions (WMLs) in the general population. However, it remains unclear whether or not the BP itself or other parameters related to the BP are associated with WMLs in hypertensive patients with well-controlled BP. We investigated the relationships of the presence of WMLs with the central systolic BP (cSBP) and estimated glomerular filtration rate (eGFR) in treated hypertensive patients. METHOD: We studied 185 hypertensive patients with median duration of hypertension, 10.0 years, whose BP is controlled to SBP and diastolic BP (DBP) of 139 ± 17 and 79 ± 10 mmHg, respectively. We measured cSBP and brain magnetic resonance imaging (MRI) was examined within 2 weeks after last BP and biological measurements. RESULTS: Patients with higher-grade WMLs, as assessed by the presence of Scheltens deep white-matter hyperintensity (SDWMH) in the frontal (grade 0-2 vs 3-6) and parietal areas (grade 0-2 vs 3-6) where small arteries are affected at earlier stage of hypertension, as well as that of Fazekas deep white-matter hyperintensity (FDWMH) (grade 2-3 vs 0-1) and Fazekas periventricular hyperintensity (FPVH) (grade 1-3 vs 0) were older, had higher serum creatinine levels, a longer duration of hypertension, and lower eGFR values. The grade of the WMLs was not associated with either the cSBP or the brachial SBP. In logistic regression analyses after adjustment for age, sex, cSBP, and hypertension duration, showed significant association between eGFR and WMLs. The patients with lower eGFR (<60 mL/minute/1.73 m(2)) tended to have higher grade WMLs. The odds ratio was 2.87 for FDWMH (P = 0.017), 1.99 for FPVH (P = 0.131), and 2.33 for SDWMH in the parietal area (P = 0.045). CONCLUSION: Presence of WMLs was associated with eGFR, but not with either the brachial SBP or cSBP in hypertensive patients with well-controlled BP.

Effects of smoking cessation on central blood pressure and arterial stiffness.

PURPOSE: Smoking affects arterial stiffness, thus causing an elevation in central blood pressure (CBP). The present study was designed to examine whether smoking cessation treatment improved CBP and arterial stiffness. PATIENTS AND METHODS: We conducted an observational study of 70 patients receiving smoking cessation treatment. Before and 60 weeks after the start of a 12-week varenicline treatment, we measured brachial blood pressure, CBP, brachial-ankle pulse wave velocity (baPWV), normalized radial augmentation index (rAIx@75), left ventricular weight, and left ventricular diastolic function of each patient. The data were compared between the patients who succeeded in quitting smoking (smoking cessation group; n = 37) and those who failed to quit smoking (smoking group; n = 33). RESULTS: Baseline characteristics were similar in both groups. Brachial blood pressure remained unchanged in both groups. CBP, baPWV, and rAIx@75 decreased significantly in the smoking cessation group, while these parameters showed no significant change in the smoking group. Thus, CBP, baPWV, and rAIx@75 showed greater decrease in the smoking cessation group than in the smoking group (CBP, -7.1 ± 1.4 mmHg vs 1.2 ± 2.7 mmHg; P < 0.01; baPWV, -204 ± 64 cm/s vs -43 ± 72 cm/s; P < 0.01; rAIx@75, -6.4 ± 2.8% vs -1.0 ± 3.9%; P < 0.01). Left ventricular weight and left ventricular diastolic function remained unchanged in both groups. CONCLUSION: Patients in the smoking cessation group showed significant improvement in CBP, baPWV, and rAIx@75. These results indicate that smoking cessation can improve arterial stiffness and CBP.

Effects of Azelnidipine plus OlmesaRTAn versus amlodipine plus olmesartan on central blood pressure and left ventricular mass index: the AORTA study.

PURPOSE: The aim of this study was to compare the effects of olmesartan combined with either azelnidipine or amlodipine on central blood pressure (CBP) and left ventricular mass index (LVMI) in hypertensive patients. PATIENT AND METHODS: Patients with brachial systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg received olmesartan monotherapy (20 mg daily) for 12 weeks. The patients were then randomly assigned to fixed-dose add-on therapy with azelnidipine (16 mg daily) or amlodipine (5 mg daily) (25 patients/group) for a further 24 weeks. CBP and LVMI were measured at baseline and at the end of the study. RESULTS: Baseline characteristics were similar in both groups. The decrease in brachial BP was similar in both groups. CBP and LVMI decreased significantly in both groups (both, P < 0.001). However, the decreases in CBP and LVMI were significantly greater with olmesartan/azelnidipine than with olmesartan/amlodipine (CBP, P < 0.001; LVMI, P = 0.002). CONCLUSIONS: These findings indicate that olmesartan/azelnidipine had greater effects on CBP and LVMI than did olmesartan/amlodipine, even though the reduction in brachial BP was similar in both groups. These differential effects on CBP and LVMI may have important implications for cardiovascular risk reduction.

Changes in cerebral perfusion in extremely LBW infants during the first 72 h after birth.

Cerebral perfusion and its relation with systemic circulation in extremely LBW (ELBW) infants in the early neonatal period are not well understood. The cerebral tissue oxygenation index (TOI) and cerebral fractional tissue oxygen extraction (FTOE) were monitored in stable 16 ELBW infants (GA <29 wk) using near-infrared spectroscopy (NIRS) at 3-6, 12, 18, 24, 36, 48, and 72 h after birth. The left ventricular end-systolic wall stress (ESWS), left ventricular ejection fraction (LVEF), left ventricular cardiac output (LVCO), and superior vena cava (SVC) flow were also measured simultaneously using echocardiography. The ESWS increased till 18 h and then decreased; LVEF, LVCO, and SVC flow decreased till 12 h and increased thereafter. The TOI decreased till 12 h and correlated with SVC flow; FTOE increased until 12 h and then decreased. These changes in variables of NIRS and echocardiographic measurements contrasted to changes in mean arterial blood pressure (MABP), which showed trends of continuous and gradual increase after birth. We conclude that even stable ELBW infants undergo evident transitional changes in cerebral oxygenation and perfusion in the early postnatal period, which may reflect changes in cardiac function and cardiac output.

Evaluation of arterial stiffness in morning hypertension under high-dose valsartan compared to valsartan plus low-dose diuretic.

Morning hypertension has been reported to be an important risk factor for cardiovascular events, and arterial stiffness bears a relationship with cardiovascular risk. The aim of this study was to evaluate whether high-dose angiotensin II receptor blocker (ARB) treatment has a more beneficial effect on arterial stiffness than regular-dose ARB plus low-dose diuretic treatment in patients with morning hypertension. Forty-three patients, in whom the home systolic blood pressure (BP) in the morning was higher than 140 mm Hg and in the evening was lower than 135 mm Hg, despite treatment with 80 mg valsartan, were randomly assigned to receive 160 mg valsartan (V group, n=22) or 80 mg valsartan plus low-dose trichlormethiazide (1 mg) (V+D group, n=21) for 6 months. There were no differences in the patient background characteristics between the two groups. There were no significant differences in BP measured at home between the two groups. The brachial-ankle pulse wave velocity (baPWV) at the time of diagnosis of morning hypertension was similar in the two groups; however, after 6 months of treatment, a greater degree of reduction of the baPWV and a greater degree of reduction of BP in the supine position were observed in the V group compared with the V+D group. Thus, though both high-dose valsartan and valsartan plus diuretic reduced the BP to a similar degree in patients with morning hypertension, high-dose valsartan exerted a greater beneficial effect on arterial stiffness than did valsartan plus diuretic.

Usefulness of indomethacin for patent ductus arteriosus in full-term infants.

The aim of this retrospective study was to evaluate the effectiveness of indomethacin therapy for patent ductus arteriosus (PDA) in full-term infants. The patients were 41 full-term infants with a PDA birth weight (BW) > or =2500 g and a gestational age (GA) > or =37 weeks. The echocardiographic evaluation and medical management of PDA in these infants was similar to that for PDA in low-birth-weight infants. Indomethacin (0.2-0.25 mg/kg/dose) was given intravenously at 12-24-hour intervals within 23 days of birth. Of the 41 infants, 12 showed complete closure, and 13 showed improvement of clinical symptoms. These 25 infants were classified as the responder group (61%). The other 16 infants, who did not show improvement in clinical symptoms, were classified as the nonresponder group. Statistical analysis revealed no difference between the two groups regarding GA, BW, Apgar score at 1 minute, minimum diameter of the DA before treatment, the average age at the initiation of treatment, and DA flow pattern. No severe adverse reactions were observed in any infant. Indomethacin therapy appears to be an effective medical treatment option for PDA in full-term symptomatic infants prior to considering surgical treatment.

Diagnosis and evaluation of febrile infants under 4 months of age in Japan by using RT-PCR for enterovirus.

OBJECTIVES AND METHODS: In order to establish an effective management for febrile infants under 4 months of age we analysed the causes of fever by using bacterial work up and a highly sensitive RT-PCR method during a 3-year-period. From February 1998 to January 2001, 263 infants under 4 months of age were admitted to our hospital because of fever (>38.0 degrees C) and enrolled in this study. RESULTS: Eighty-nine cases (33.8%) were diagnosed as lower respiratory infections, and 62 (23.5%) as urinary tract infections. Aseptic meningitis was found in 35 cases (13.2%) and fever of unknown origin in 22 (8.3%). Sepsis and purulent meningitis were found in three and two infants, respectively. Aseptic meningitis was the most common disease in infants below 30 days. Aseptic meningitis and fever of unknown origin revealed no seasonable tendency. Twelve cases out of 20 tested infants with aseptic meningitis showed positive results for enterovirus in CSF. CONCLUSION: Clinicians should consider age, sex and seasons when evaluating and treating infants with fever. Previously lumbar puncture, urinalysis and chest X-ray were recommended to avoid useless assays. These results also revealed that RT-PCR is a useful and significant assay to establish an exact diagnosis in very young infants.

Monitoring of cerebral oxygenation during hypoxic gas management in congenital heart disease with increased pulmonary blood flow.

In the preoperative management of congenital heart disease (CHD) with increased pulmonary blood flow, hypoxic gas management to control pulmonary blood flow is useful. However, the cerebral oxygenation state has rarely been studied, and there is concern about neurologic development. In eight infants with CHD accompanied by increased pulmonary blood flow, hypoxia was induced after a 1-h baseline period in room air (FiO2, 0.21). The infants were simultaneously monitored in both the front-temporal region and the right-brachial region for 90 min using near-infrared spectroscopy (NIRS). The minimum SaO2 (pulse oximetry) after hypoxic gas administration was 80.8 +/- 2.9% when the minimum FiO2 was 16.2 +/- 1.1%. With a decrease in SaO2, oxy-Hb (O2Hb) decreased and total Hb [cHb: O2Hb + deoxy-Hb (HHb)] increased in both regions in the majority of infants. HHb increased in both regions with a decrease in SaO2. The maximum change in the tissue oxygenation index (TOI: O2Hb/cHb x 100) was -8.3 +/- 2.6% in the front-temporal region and -3.6 +/- 2.3% in the right-brachial region. Cerebral oxygenation decreased despite an increase in cerebral blood flow during hypoxic gas management. The change in TOI was < or =10% when the SaO2 was > or =80%. Safer control of SaO2 should be maintained over 80% for hypoxia management in CHD based on the results of the present study.

Effects of rapid rewarming on cerebral nitric oxide production and cerebral hemodynamics after hypothermia therapy for kainic acid-induced seizures in immature rabbits.

BACKGROUND: The aim of the present study was to investigate whether rapid rewarming after hypothermia therapy during seizures alters the endogenous nitric oxide (NO) production in and around hippocampus, cortical cerebral blood flow (cCBF), and mean arterial blood pressure (MABP) in immature rabbits. METHODS: The hypothermic rabbits (rectal temperatures, 33 degrees C) were given kainic acid (KA; 12 mg/kg, i.v; at 0 min), followed by cooling (33 degrees C) for 60 min (at 60 min), then either rewarming (RW; 33-37 degrees C) was started (KA[+]RW[+] group, n = 7) or cooling was continued (KA[+]RW[-] group, n = 7) for another 60 min (at the end 120 min). In the KA(-)RW(+) group (n = 5), 0.5 mL normal saline was given (at time 0 min), followed by cooling (33 degrees C) for 60 min (at 60 min), then rewarming to 37 degrees C was started with observation for another 60 min (at the end 120 min). NO production in and around hippocampus was continuously measured by an NO-selective electrode, cCBF by laser Doppler flowmetry, cortical electroencephalogram (EEG), rectal and cerebral temperatures, and MABP during the experiment. Comparisons were made of these parameters between the values at 60 min and 120 min after the KA administrations. RESULTS: KA administration induced abnormal discharges in both KA(+)RW(+) and KA(+)RW(-) groups at the same degree. The KA(+)RW(+) group had a significant increase in %NO, and significant decreases in %cCBF and MABP after rapid rewarming, compared with before rewarming. In the KA(+)RW(-) group, there were no significant changes in %NO, %cCBF, and MABP between values at 60 and 120 min. These changes after rapid rewarming in the KA(+)RW(+) group were different from those with only elevation in brain temperature from 33 to 37 degrees C without seizures (KA[-]RW[+] group). CONCLUSIONS: These results suggest that rapid rewarming after hypothermia therapy induces an increase in the NO production in and around hippocampus and the decreases in cCBF and MABP during seizures in immature rabbits.