Adaptive servo-ventilation therapy reduces hospitalization rate in patients with severe heart failure.

INTRODUCTION: Adaptive servo-ventilation (ASV) therapy is a recently developed non-pharmacological therapy that has been reported to improve cardiac function and survival in patients with severe congestive heart failure (CHF). However, a recent large randomized study suggested that ASV does not improve survival in patients with reduced ejection fraction. It remains unclear whether ASV treatment can reduce the hospitalization rate of CHF patients. We thus examined the frequency of hospital admission before and after initiation of ASV therapy in patients with CHF. METHODS AND RESULTS: Hospitalization frequencies during the 12months before and 12months after initiation of ASV therapy (24 consecutive months) were retrospectively compared in 44 consecutive patients with severe CHF. The admission frequency decreased from 1.9±1.4 admissions in the 12months before ASV to 1.1±1.6 admissions in the 12months after ASV initiation (P<0.001). The decrease tended to be greater in those patients with more frequent hospitalizations before ASV initiation. CONCLUSION: ASV therapy reduces hospital admissions in patients with severe CHF who are receiving maximum medical treatment.

Hemodynamic response during standing test after blood donation can predict the late phase vasovagal reaction.

A major complication of blood donation is vasovagal reaction (VVR) with or without syncope. VVR occurs not only in the early phase, but also in the late phase after blood donation. We previously reported the hemodynamic characteristics of blood donors susceptible to early phase VVR. In the present study, we investigated the hemodynamic characteristics of those who developed late VVR. Ninety-six healthy volunteers donating 400 ml of whole blood were studied. After asking about their physical condition or routine questions for blood donation, blood pressure (BP) and heart rate (HR) were recorded while the donors were kept standing up for 3 min before and after blood collection. Questionnaires were distributed to all donors for reporting late VVR symptoms within 24 h. Those with younger age and lower diastolic blood pressure were more susceptible to late VVR (both p < 0.05). Furthermore, we identified the increase in HR during the standing test after blood collection as a good predictor of late VVR (odds ratio 1.063, 95 % CI 1.005-1.124; p = 0.031). Also, analysis of questions asked before donation revealed that significantly more donors considered themselves as sensitive to pain in the late VVR group (Odds ratio 0.070, 95 % CI 0.008-0.586; p = 0.014). Excessive HR response to standing after blood collection and subjective sensitivity to pain as well as younger age and lower diastolic BP may be useful to detect donors at high risk for late VVR.

Prevalence of Sleep Disordered Breathing among Patients with Nocturia at a Urology Clinic.

OBJECTIVE: We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia. METHODS: Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment. RESULTS: SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy. CONCLUSION: SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.

Enhancement of cardiac performance by bilevel positive airway pressure ventilation in heart failure.

BACKGROUND: Recent studies have reported the clinical usefulness of positive airway pressure ventilation therapy with various kinds of pressure support compared with simple continuous positive airway pressure (CPAP) for heart failure patients. However, the mechanism of the favorable effect of CPAP with pressure support can not be explained simply from the mechanical aspect and remains to be elucidated. METHODS AND RESULTS: In 18 stable chronic heart failure patients, we performed stepwise CPAP (4, 8, 12 cm H(2)O) while the cardiac output and intracardiac pressures were continuously monitored, and we compared the effects of 4 cm H(2)O CPAP with those of 4 cm H(2)O CPAP plus 5 cm H(2)O pressure support. Stepwise CPAP decreased cardiac index significantly in patients with pulmonary arterial wedge pressure (PAWP) <12 mm Hg (n = 10), but not in those with PAWP ≥12 mm Hg (n = 8). Ventilation with CPAP plus pressure support increased cardiac index slightly but significantly from 2.2 ± 0.7 to 2.3 ± 0.7 L min(-1) m(-2) (P = .001) compared with CPAP alone, regardless of basal filling condition or cardiac index. CONCLUSIONS: Our results suggest that CPAP plus pressure support is more effective than simple CPAP in heart failure patients and that the enhancement might be induced by neural changes and not simply by alteration of the preload level.

Studies on the mechanism of antihypertensive action by nicotianamine.

Nicotianamine (NA), which is obtained from vegetables, lowers blood pressure through the renin-angiotensin system, and we clarified that NA preferentially inhibits the activity of angiotensin I-converting enzyme (ACE)-a zinc-containing enzyme. In this study, we elucidated the mechanism of antihypertensive action of NA through the Magnus method by using rat aortic blood vessels. Angiotensin I-induced contractions were inhibited by NA in a concentration-dependant manner. Because NA did not inhibit angiotensin II-induced contractions, it was believed that NA inhibited ACE activity in vascular smooth muscles. NA did not affect KCl-induced contractions, but it affected norepinephrine-induced contractions to a small extent. NA exerted similar effects on endothelium-denuded and endothelium-intact blood vessels. Therefore, the antihypertensive action of NA did not play a role in the opening of voltage-dependent calcium channels, but this effect influenced vasoconstriction by the activation of α-adrenergic receptors. These results suggest that after absorption from the intestinal tract, NA may exert antihypertensive effects via 2 mechanisms: direct inhibition of ACE in vascular smooth muscle and activation of α-adrenergic receptors.

Nicotianamine preferentially inhibits Angiotensin I-converting enzyme.

Nicotianamine (NA) is a nonprotein amino acid that inhibits the angiotensin I-converting enzyme (ACE) in the renin-angiotensin system (RAS). The purpose of this study is to prove that NA contributes to the suppression of hypertension by preferential inhibition of ACE. On comparison with EDTA-a chelator-we found that the inhibition pattern of NA for ACE is that of mixed inhibition and that NA exhibits weak chelation effects for zinc, copper, and cobalt ions. Therefore, we investigated whether NA inhibited zinc-containing enzymes other than ACE in vitro. The results revealed that NA does not inhibit leucine aminopeptidase or alkaline phosphatase in rat serum. On the other hand, NA demonstrated specific inhibitory effects for rat serum ACE and aortic ACE. These results suggest that the preferential inhibition of circulatory and tissue ACE by NA can contribute to the suppression of hypertension.

Reduction of salt sensitivity in stroke-prone spontaneously hypertensive rats administered an AT1 receptor antagonist during suckling.

BACKGROUND: In this study, antihypertensive therapy was started during suckling and the effect on blood pressure (BP) and salt sensitivity of stroke-prone spontaneously hypertensive rats (SHRSP) was determined. METHODS: The SHRSP were treated with an AT1 receptor antagonist (losartan: 100 mg/L in drinking water) from 2 to 4 weeks of age. After stopping treatment at 4 weeks of age, the control group and the losartan group were fed a commercial diet with tap water ad libitum until 10 weeks of age. Both the control and losartan groups were switched to 1% saline at the age of 10 weeks. RESULTS: Salt loading was started at 10 weeks of age, with BP levels of 203+/-3 and 199+/-6 mm Hg for the control group and the losartan group, respectively, at that age. After 4 weeks of salt loading, BP levels were 253+/-7 mm Hg in the control group and 242+/-5 mm Hg in the losartan group, showing a mild elevation in the losartan group. The life span of the losartan group (104+/-78 days) was significantly greater than that of the control group (37+/-17 days). Plasma aldosterone concentrations of the losartan group were lower than those of the control group at 4 and 15 weeks of age. CONCLUSIONS: We have demonstrated the renin-angiotensin-aldosterone system may play a key role in the establishment of end-organ salt sensitivity, and the period of lactation in critical for salt sensitivity in later life.

Depressor effect induced by dipeptide, Val-Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin-angiotensin system.

1. In the present study, the depressor action of the dipeptide Val-Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross-mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM). 2. Single oral administration of Val-Tyr (0.1 mg/g) to 11-week-old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val-Tyr absorbed acted on the enhanced human renin-angiotensin system (RAS). 3. After Val-Tyr administration, an approximate eightfold higher increment of plasma Val-Tyr was observed at 1 h (3406 +/- 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val-Tyr returned to baseline levels at 6 h. 4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val-Tyr concentrations, suggesting that that the long-lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val-Tyr and not by transient suppression of the circulatory RAS. 5. Ageing of the THM greatly affected the depressor action of Val-Tyr, with no significant reduction in blood pressure observed in 18- and 24-week-old THM.