Inversion of Qubit Energy Levels in Qubit-Oscillator Circuits in the Deep-Strong-Coupling Regime.

We report on experimentally measured light shifts of superconducting flux qubits deep-strongly coupled to LC oscillators, where the coupling constants are comparable to the qubit and oscillator resonance frequencies. By using two-tone spectroscopy, the energies of the six lowest levels of each circuit are determined. We find huge Lamb shifts that exceed 90% of the bare qubit frequencies and inversions of the qubits' ground and excited states when there are a finite number of photons in the oscillator. Our experimental results agree with theoretical predictions based on the quantum Rabi model.

Driven dynamics and rotary echo of a qubit tunably coupled to a harmonic oscillator.

We have investigated the driven dynamics of a superconducting flux qubit that is tunably coupled to a microwave resonator. We find that the qubit experiences an oscillating field mediated by off-resonant driving of the resonator, leading to strong modifications of the qubit Rabi frequency. This opens an additional noise channel, and we find that low-frequency noise in the coupling parameter causes a reduction of the coherence time during driven evolution. The noise can be mitigated with the rotary-echo pulse sequence, which, for driven systems, is analogous to the Hahn-echo sequence.

Hamiltonian of a flux qubit-LC oscillator circuit in the deep-strong-coupling regime.

We derive the Hamiltonian of a superconducting circuit that comprises a single-Josephson-junction flux qubit inductively coupled to an LC oscillator, and we compare the derived circuit Hamiltonian with the quantum Rabi Hamiltonian, which describes a two-level system coupled to a harmonic oscillator. We show that there is a simple, intuitive correspondence between the circuit Hamiltonian and the quantum Rabi Hamiltonian. While there is an overall shift of the entire spectrum, the energy level structure of the circuit Hamiltonian up to the seventh excited states can still be fitted well by the quantum Rabi Hamiltonian even in the case where the coupling strength is larger than the frequencies of the qubit and the oscillator, i.e., when the qubit-oscillator circuit is in the deep-strong-coupling regime. We also show that although the circuit Hamiltonian can be transformed via a unitary transformation to a Hamiltonian containing a capacitive coupling term, the resulting circuit Hamiltonian cannot be approximated by the variant of the quantum Rabi Hamiltonian that is obtained using an analogous procedure for mapping the circuit variables onto Pauli and harmonic oscillator operators, even for relatively weak coupling. This difference between the flux and charge gauges follows from the properties of the qubit Hamiltonian eigenstates.

Reverse white-coat effect as an independent risk for left ventricular concentric hypertrophy in patients with treated essential hypertension.

Recent studies have shown that the converse phenomenon of white-coat hypertension called 'reverse white-coat hypertension' or 'masked hypertension' is associated with poor cardiovascular prognosis. We assessed the hypothesis that this phenomenon may specifically influence left ventricular (LV) structure in treated hypertensive patients. A total of 272 outpatients (mean age, 65 years) with chronically treated essential hypertension and without remarkable white-coat effect were enrolled. Patients were classified into two groups according to office and daytime ambulatory systolic blood pressure (SBP); that is subjects without (Group 1: office SBP > or =daytime SBP, n=149) and with reverse white-coat effect (Group 2: office SBP

Association of single nucleotide polymorphisms in endothelin family genes with the progression of atherosclerosis in patients with essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictive peptide and its activity is mediated by the receptors ET type A (EDNRA) and ET type B (EDNRB). Although ET-1 is thought to play an important role in the development of atherosclerosis, it remains unclear whether polymorphisms of ET-1 family genes, including the ET-1 gene (EDN1), EDNRA, EDNRB and the genes for endothelin converting enzymes 1 and 2 (ECE1 and ECE2), are associated with the progression of atherosclerosis. We investigated the relationship between 11 single nucleotide polymorphisms (SNPs) of ET-1 family genes (including three in EDN1, one in EDNRA, two in EDNRB, four in ECE1 and one in ECE2) and atherosclerotic changes assessed using pulse wave velocity (PWV) and carotid ultrasonography in 630 patients with essential hypertension (EHT). In male subjects, we found significant differences in brachial-ankle PWV (baPWV) in additive and recessive models in EDNRB-rs5351 after Bonferroni correction. Also in male subjects, there were significant differences in mean intima-media thickness (IMT) in additive and recessive models in EDNRA-rs5333 after Bonferroni correction. We found no significant correlation between any SNPs in the ET family genes and baPWV, IMT and Plaque score (PS) in female subjects. Furthermore, after multiple logistic regression analysis, only EDNRB-rs5351 indicated as an independent risk of atherosclerosis in male hypertensive subjects. Of the endothelin-related genes, EDNRB-rs5351 was the most susceptible SNP associated with atherosclerosis in male hypertensives, and the genetic background may be involved in the progression of atherosclerosis in EHT patients.

Preventive effect of renin-angiotensin system inhibitors on new-onset atrial fibrillation in hypertensive patients: a propensity score matching analysis.

It is still controversial whether treatment with renin-angiotensin system (RAS) inhibitors reduces the risk of incident atrial fibrillation (AF). This longitudinal observational study was performed to investigate the confounder-independent effects of RAS inhibitors on new-onset AF in hypertensive patients. Among 1263 consecutive hypertensive patients who underwent echocardiography, 964 eligible patients (mean age, 63 years) were enrolled as the study population. Forty-nine patients developed new-onset AF during the follow-up period (mean: 4.6 years). Kaplan-Meier analysis showed that the cumulative AF event rate was lower in patients receiving RAS inhibitors than in patients without these drugs, but the difference between these two groups was not significant (P=0.057). Since the use of RAS inhibitors was influenced by concomitant diabetes, chronic kidney disease and left ventricular hypertrophy, propensity score matching (1:1) was employed to minimize the influence of selection bias for RAS inhibitors. Clinical and echocardiographic parameters showed no significant differences between the propensity score-matched groups with and without RAS inhibitor therapy (both n=326), but the cumulative AF event rate was significantly lower in the group receiving RAS inhibitors (P=0.013). Univariate and multivariate Cox regression analyses also revealed that RAS inhibitor therapy was associated with a significantly lower risk of new-onset AF during the follow-up period. In conclusion, this propensity score matching study demonstrated that the incidence of new-onset AF was lower in hypertensive patients receiving RAS inhibitor therapy.

Microalbuminuria and deterioration of renal function after elective repair of infrarenal abdominal aortic aneurysm.

AIMS: Renal dysfunction affects the prognosis of patients after aortic surgery. However, the factors associated with the postoperative deterioration of renal function has not been clarified precisely. METHOD: We prospectively examined renal function in 80 patients (age: 73 +/- 7 years, 66 males) who required the elective repair of infrarenal abdominal aortic aneurysm (AAA). Serum creatinine (Scr) was measured. 24-h-creatinine clearance (Ccr) and urinary albumin excretion (UAE) were determined. Renal volume and mean renal length were calculated using the data obtained by ultrasonography. 48 patients showed normal UAE (< 30 mg/day), and 24 had microalbuminuria (30-300 mg/day) and 8 had overt proteinuria (> 300 mg/day). Scr were 0.9 +/- 0.4, 1.0 +/- 0.3 and 2.1 +/- 1.3 mg/dl, respectively. RESULTS: On Day 5 after surgery, 12 patients (15%) showed deterioration of renal function as defined either by an increase in Scr (> or = 0.5 mg/dl) or by a decrease in Ccr > or =20%). The acute deterioration of renal function was related to mean renal volume, mean renal length, duration of operation and the use of antibiotics. At Month 12 after surgery, Scr increased in the overt proteinuria group. The deterioration of renal function at Month 12 was found in 8 patients (10%) with microalbuminuria or overt proteinuria, and related to preoperative Ccr, UAE, mean renal volume, mean renal length, smoking status and blood pressure. CONCLUSION: We conclude that the deterioration of renal function occurred in considerable number of patients with AAA after elective operation on acute and chronic phase, although the development of end-stage renal failure is rare. Factors related to the acute and late deterioration appears to be different. UAE and renal size should be measured, even if Scr is in normal range at preoperative observation.

The role of endocytic l1 trafficking in polarized adhesion and migration of nerve growth cones.

Motility of the nerve growth cone is highly dependent on its dynamic interactions with the microenvironment mediated by cell adhesion molecules (CAMs). These adhesive interactions can be spatially regulated by changing the density and avidity of CAMs on the growth cone. Previous studies have shown that L1, a member of the immunoglobulin superfamily of CAMs, is endocytosed at the central domain of the growth cone followed by centrifugal vesicular transport and reinsertion into the plasma membrane of the leading edge. The present paper focuses on the functional significance of endocytic L1 trafficking in dorsal root ganglia neurons in vitro. We demonstrate that the rate of L1-based neurite growth has a positive correlation with the amount of endocytosed L1 in the growth cone, whereas stimulation of neurite growth via an N-cadherin-dependent mechanism does not increase L1 endocytosis. A growth cone that migrates on an L1 substrate exhibits a steep gradient of L1-mediated adhesion (strong adhesion at the growth cone's leading edge and weak adhesion at the central domain). This gradient of L1 adhesion is attenuated after inhibition of L1 endocytosis in the growth cone by intracellular loading of a function-blocking antibody against alpha-adaptin, a subunit of the clathrin-associated AP-2 adaptor. Inhibition of L1 endocytosis by this antibody also decreased the rate of L1-dependent growth cone migration. These results indicate that the growth cone actively translocates CAMs to create spatial asymmetry in adhesive interactions with its environment and that this spatial asymmetry is important for growth cone migration.

Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure.

BACKGROUND: Ghrelin is a novel growth hormone (GH)-releasing peptide that may also induce vasodilation and stimulate feeding through GH-independent mechanisms. We investigated whether ghrelin improves left ventricular (LV) dysfunction and attenuates cardiac cachexia in rats with chronic heart failure (CHF). METHODS AND RESULTS: Ligation of the left coronary artery or sham operation was performed; 4 weeks after surgery, rat ghrelin (100 microg/kg SC BID) or saline was administered for 3 weeks. Echocardiography and cardiac catheterization were performed. Serum GH and insulin-like growth factor-1 were significantly higher in both CHF and sham rats treated with ghrelin than in those given placebo (P<0.05 for both). CHF rats given placebo showed an impaired increase in body weight compared with sham rats given placebo (P<0.05). CHF rats treated with ghrelin, however, showed a significantly greater increase in body weight than those given placebo (+10% versus +3%, P<0.05). They showed significantly higher cardiac output (315+/-49 versus 266+/-31 mL. min(-1). kg(-1), P<0.05) and LV dP/dt(max) (5738+/-908 versus 4363+/-973 mm Hg/s, P<0.05) than CHF rats given placebo. Ghrelin increased diastolic thickness of the noninfarcted posterior wall, inhibited LV enlargement, and increased LV fractional shortening in CHF rats (from 15+/-3% to 19+/-3%, P<0.05). CONCLUSIONS: Chronic subcutaneous administration of ghrelin improved LV dysfunction and attenuated the development of LV remodeling and cardiac cachexia in rats with CHF.

Production and secretion of adrenomedullin in cultured rat cardiac myocytes and nonmyocytes: stimulation by interleukin-1beta and tumor necrosis factor-alpha.

The present study investigated the secretion level and gene expression of adrenomedullin (AM), a novel vasorelaxant peptide, in cultured neonatal rat cardiac myocytes and nonmyocytes, and the effects of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF alpha) on its production and secretion in these cells. Under serum-free conditions, both myocytes and nonmyocytes secreted immunoreactive (ir-) AM into the culture medium in a time-dependent manner. The secretion rates of ir-AM from myocytes and nonmyocytes per 10(5) cells were almost equivalent. The expression of AM messenger RNA was also observed in cultured myocytes and nonmyocytes. The peptide secretion and messenger RNA level of AM in cardiac myocytes were increased after stimulation with IL-1beta. In nonmyocytes, IL-1beta and TNF alpha remarkably augmented both the release of ir-AM into the medium and AM gene expression after 24 and 48 h of incubation. These observations indicate that cardiac ventricular cells (i.e. myocytes and nonmyocytes) actively produce AM and also suggest that cytokines such as IL-1beta and TNF alpha regulate the gene expression and secretion of this peptide in the ventricles. On the basis of these results and the findings that IL-1beta and TNF alpha are involved in heart failure and cardiac hypertrophy, AM may play a role as an autocrine/paracrine modulator in some cardiac disorders.

Cardiac production and secretion of adrenomedullin are increased in heart failure.

Plasma adrenomedullin (AM) levels are reportedly increased in heart failure, but whether the cardiac production and secretion of AM is increased in heart failure remains unknown. To investigate the sites of production and secretion of AM in heart failure, we measured plasma AM levels and peptide and mRNA levels of AM in various tissues in rats with heart failure. We also examined whether the heart actually secretes AM into the circulation in patients with heart failure. We measured plasma and tissue AM levels by specific radioimmunoassay and AM mRNA by Northern blot analysis in rats with heart failure produced by aortocaval fistula. We also measured plasma AM levels in the coronary sinus and aorta in patients with left ventricular dysfunction before and after rapid right ventricular pacing. The increase in plasma AM levels in heart failure rats correlated with ventricular weight. Tissue AM levels were increased in the heart and lungs but not in the kidneys or adrenals of rats with heart failure. Similarly, tissue AM mRNA levels were also increased in the heart and lungs of heart failure rats. Plasma AM levels were higher in the coronary sinus than in the aorta in patients with left ventricular dysfunction. Rapid right ventricular pacing increased plasma atrial natriuretic peptide but not AM. These results suggest that plasma AM levels are increased in heart failure in proportion to the severity of heart failure and that cardiac production and secretion of AM is increased in heart failure rats. The lung may be another site for increased production of AM in heart failure rats. Human failing heart actually secretes AM into the circulation, and the regulation of AM secretion appears to differ from that of atrial natriuretic peptide.

Ventricular adrenomedullin levels correlate with the extent of cardiac hypertrophy in rats.

We investigated the pathophysiological significance of adrenomedullin (AM) in the development of left ventricular hypertrophy (LVH). LVH was produced by aortic banding (AB) in rats. The left ventricular weight/body weight (LV/BW) ratio, ventricular AM peptide and mRNA levels, and hemodynamics were measured at 1, 3, 7, and 21 days after the operation. Both LV/BW ratio and ventricular AM levels showed a significant increase from 1 day after the operation in the AB rats versus the sham-operated rats. Both increased in a time-dependent manner. The ventricular AM levels correlated with the LV/BW ratio (r=0.76, P<0.01). The AM mRNA levels were highly expressed at 1 day after the operation in the AB rats but showed no difference from 3 to 21 days after the operation between the AB and sham groups. The plasma AM levels showed a peak at 1 day after the operation in both groups. Then, we treated AB rats with an angiotensin-converting enzyme inhibitor (quinapril) in 2 doses (1 and 10 mg. kg-1. d-1) for 21 days. The quinapril treatment attenuated similarly both the LV/BW ratio and the ventricular AM levels. We also assessed the effects of AM and hydralazine administration for 7 days on the LV/BW ratio and hemodynamics of AB rats. Both AM and hydralazine administration reduced the blood pressure by approximately 10% compared with the nontreated AB rats, but a reduction of the LV/BW ratio was observed only in the AM-treated group (P<0.05). These results suggest that ventricular AM levels are elevated by chronic pressure overload in a time-dependent manner concomitant with the extent of LVH and that AM may play a pathophysiological role in the development of LVH in chronic pressure overload.

Inhibitory regulation of hypertrophy by endogenous atrial natriuretic peptide in cultured cardiac myocytes.

Atrial natriuretic peptide (ANP) may function as an endogenous regulator of cardiac hypertrophy, because the natriuretic peptide receptor has been found in the heart and because mice lacking its receptor have been shown to have a markedly elevated ventricular mass. We examined the role of endogenous ANP in cardiac hypertrophy in vitro. The effects of the blockade of endogenous ANP by its receptor antagonist, HS-142-1, on cell hypertrophy were investigated with the use of cultured neonatal rat ventricular myocytes. HS-142-1 increased the basal and phenylephrine (PE, 10(-5) mol/L)-stimulated protein syntheses in a concentration-dependent manner (1 to 300 microg/mL). A significant increase in the cell size of myocytes was also induced by this antagonist. In addition, the expression levels of skeletal alpha-actin, beta-myosin heavy chain, and ANP genes, markers of hypertrophy, were partially elevated by treatment with HS-142-1 (100 microg/mL) under nonstimulated or PE-stimulated conditions. A cGMP-specific phosphodiesterase inhibitor, zaprinast (5x10(-4) mol/L), and a cGMP analogue (10(-4) mol/L) suppressed the basal and PE-stimulated protein syntheses. Our observations suggest that endogenous ANP inhibits cardiac myocyte hypertrophy under basal and PE-stimulated conditions, probably through a cGMP-dependent process. ANP may play a role as an autocrine factor in the regulation of cardiac myocyte growth.

Relationship between left ventricular geometry and natriuretic peptide levels in essential hypertension.

Previous studies have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in essential hypertension. However, whether left ventricular geometry affects plasma ANP and BNP levels remains unknown. To investigate the effect of left ventricular geometry on plasma ANP and BNP levels in essential hypertension, we measured plasma ANP and BNP levels in 90 patients with essential hypertension. All patients were hospitalized, and fasting blood samples were obtained in the early morning after 30 minutes of bed rest. Plasma ANP and BNP levels were measured by immunoradiometric assay. Hypertensive patients were classified into four groups according to echocardiographic findings that showed normal geometry, concentric remodeling, eccentric hypertrophy, or concentric hypertrophy. Mean plasma ANP and BNP levels in all essential hypertensive patients were higher than those in age-matched normotensive control subjects. Plasma ANP levels in hypertensive patients with concentric remodeling, eccentric hypertrophy, and concentric hypertrophy were higher than in normotensive control subjects, although there were no differences between normotensive subjects and hypertensive patients with normal geometry. Plasma BNP levels tended to be higher in hypertensive patients with normal geometry, concentric remodeling, and eccentric hypertrophy than in normotensive control subjects; however, the differences were not significant. Plasma BNP levels and BNP/ANP ratio were specifically higher in concentric hypertrophy. There were significant correlations between ANP and left ventricular mass index, relative wall thickness, interventricular septal thickness, posterior wall thickness, and mean arterial pressure. Plasma BNP levels significantly correlated with relative wall thickness, interventricular septal thickness, posterior wall thickness, and left ventricular mass index but not with mean arterial pressure. In addition, plasma BNP levels were well correlated with ANP levels, and the slope for the linear regression model was steeper in concentric hypertrophy than in the other four groups. These results show that plasma ANP and BNP levels are increased in essential hypertensive patients with left ventricular hypertrophy. Furthermore, BNP secretion is augmented to a greater extent in concentric hypertrophy. Thus, measurement of plasma ANP and BNP levels may be useful for the detection of concentric left ventricular hypertrophy in patients with essential hypertension.

Plasma levels of natriuretic peptides and adrenomedullin in elderly hypertensive patients: relationships to 24 h blood pressure.

OBJECTIVE: The aim of this study was to investigate the relationships between levels of natriuretic peptides and adrenomedullin and 24 h blood pressure levels in elderly hypertensives. DESIGN AND METHODS: We performed both 24 h ambulatory blood pressure monitoring and measurement of plasma levels of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and adrenomedullin in 118 asymptomatic hypertensive elderly (> 60 years old) patients. We classified the subjects into groups with isolated clinic hypertension (n = 40) and sustained hypertension (n = 78). We also measured the levels of these peptides in 37 elderly normotensive subjects. RESULTS: Plasma ANP and BNP levels were slightly increased in patients with isolated clinic hypertension compared with elderly normotensives. Among the hypertensives, plasma ANP and BNP levels were more closely related to 24 h blood pressure levels than to office blood pressure levels. Sustained hypertensives showed significantly increased plasma levels of ANP and BNP compared with isolated clinic hypertensives, while adrenomedullin levels were similar in the two groups. Elderly hypertensives with left ventricular hypertrophy detected by electrocardiography had significantly higher levels of ANP and BNP, and higher BNP/ANP ratios than those without left ventricular hypertrophy, while there was no significant difference in adrenomedullin levels between the two groups. CONCLUSIONS: Our results suggest that measurements of ANP and BNP may be useful in detecting left ventricular hypertrophy and in differentiating isolated clinic hypertension from sustained hypertension in elderly hypertensive patients.

Molecular forms of plasma and urinary adrenomedullin in normal, essential hypertension and chronic renal failure.

OBJECTIVES: Human adrenomedullin precursor is converted to glycine-extended adrenomedullin (AM-Gly), an intermediate inactive form of adrenomedullin. Subsequently, AM-Gly is converted to active form of mature adrenomedullin (AM-m). The aim of the present study was to investigate (i) whether sex or age influences plasma and urinary AM-m and AM-Gly levels in normal subjects; (ii) the daytime variability of plasma AM-m and AM-Gly levels in normal subjects; (iii) AM-m and AM-Gly levels and its ratio in plasma and urine in normal subjects, individuals with essential hypertension (HT), and chronic renal failure (CRF); and (iv) the ratio of AM-m and AM-total (T) in plasma of various veins and aorta. METHODS: We measured plasma levels and urinary excretions of AM-m, AM-Gly and AM-T (AM-m + AM-Gly) by recently developed immunoradiometric assay in normal subjects (n = 81), HT (n = 28) and CRF (n = 30). We also determined the molecular forms of plasma adrenomedullin taken from various sites during angiography in patients with suspected renovascular hypertension (n = 9). RESULTS: There were no differences in plasma and urinary excretions of two molecular forms of adrenomedullin among sexes or ages in normal subjects. There was no daytime variation of plasma two molecular forms of adrenomedullin in normal subjects. Plasma AM-m, AM-Gly and AM-T levels were increased in patients with HT and CRF compared with normal subjects, whereas urinary AM-m, AM-Gly and AM-T excretions were decreased in patients with HT and CRF compared with normal subjects. Urinary AM-m: AM-T ratios were significantly higher than plasma AM-m: AM-T ratios. Plasma AM-m and AM-T levels taken from various veins were similar, and they were significantly higher than those of aorta, although there were no differences in plasma AM-Gly levels between aorta and veins. CONCLUSIONS: These results suggest that in normal subjects, and individuals with HT and CRF: (i) plasma and urinary excretions of AM-m and AM-Gly are not affected by age or sex; (ii) AM-m in parallel with AM-Gly is increased; (iii) urine contains a higher percentage of active adrenomedullin than plasma; and (iv) plasma AM-m may be partly metabolized in the lung.

Effect of neutral endopeptidase inhibitor on endogenous atrial natriuretic peptide as a paracrine factor in cultured cardiac fibroblasts.

1. Cardiac remodelling is a fundamental response to hypertension, myocardial infarction and chronic heart failure, and involves cardiac fibroblast proliferation and production of extracellular matrix components such as collagen. The present study was performed to examine the role of endogenous atrial natriuretic peptide (ANP) as a possible paracrine factor for cardiac fibroblasts, and to examine the effects of three neutral endopeptidase (NEP) inhibitors, thiorphan, phosphoramidon and ONO-BB-039-02 (ONO-BB) on endogenous ANP-induced changes in collagen synthesis by cultured neonatal rat cardiac fibroblasts. 2. Each NEP inhibitor singly had no significant effect on collagen synthesis by cardiac fibroblasts, except for maximum concentration (10(-3) M) of thiorphan. 3. Exogenous ANP inhibited collagen synthesis in a concentration-dependent manner (10(-8) - 10(-6) M). Thiorphan (10(-4) and 10(-3) M) and phosphoramidon (10(-5) and 10(-4) M) enhanced the ANP (10(-7) M)-induced decrease in collagen synthesis. ONO-BB (10(-5) and 10(-4) M) slightly enhanced the ANP-induced decrease in collagen synthesis. 4. Myocyte-conditioned medium (MC-CM), as well as exogenous ANP, inhibited collagen synthesis dose-dependently. The decrease in collagen synthesis at 100% MC-CM was augmented by thiorphan (10(-3) M), phosphoramidon (10(-4) M) and ONO-BB (10(-4) M). 5. HS-142-1, a natriuretic peptide receptor antagonist, significantly reduced the MC-CM plus thiorphan- and MC-CM plus ONO-BB-induced decrease in collagen synthesis, by 92 and 62%, respectively and showed a tendency to attenuate the MC-CM plus phosphoramidon-induced decrease in collagen synthesis by 40%. 6. Our observations suggested that endogenous ANP released from cardiomyocytes inhibited collagen synthesis as a paracrine factor and that NEP inhibitors enhanced the activity of this peptide in cardiac fibroblasts.

Atrial natriuretic peptide secretion and body fluid balance after bilateral atrial appendectomy by the maze procedure.

OBJECTIVES: One of the earliest recognized postoperative complications of the maze procedure was the fluid retention in the immediate postoperative period. Routine postoperative administration of diuretics markedly reduces the frequency and severity of the fluid retention. However, the cause of the abnormal fluid balance is still uncertain. METHODS: We evaluated 24 patients: 15 patients underwent the maze procedure (maze group) and 9 patients did not (nonmaze group). Blood samples were obtained before and in the time course after operation for atrial natriuretic peptide measurement. To evaluate the influence of atrial natriuretic peptide on the body fluid balance, we also measured the amount of body fluid balance and the total doses of furosemide and dopamine administered after operation. To examine the effect of the maze procedure on atrial natriuretic peptide secretion in chronic phase, we measured plasma atrial natriuretic peptide levels during dynamic exercise in 21 patients who had undergone cardiac operations 2 years before. RESULTS: Plasma atrial natriuretic peptide levels in the nonmaze group significantly increased after operation. In contrast, plasma atrial natriuretic peptide levels in the maze group did not increase, and these levels were significantly lower than in the nonmaze group. Although significantly greater doses of furosemide and dopamine were administered to the maze group than to the nonmaze group, the body fluid balance in the maze group was comparable with that in the nonmaze group in the early postoperative period. The response of atrial natriuretic peptide secretion by exercise was significantly attenuated in the maze group (n = 12) compared with the nonmaze group (n = 9) even 2 years after surgery, although there were no significant differences in heart rate or blood pressure during exercise between two groups. CONCLUSIONS: These results suggest that the maze procedure attenuates atrial natriuretic peptide secretion in the early postoperative period and persists in chronic phase. This attenuated atrial natriuretic peptide secretion may reduce the ability of the kidneys to handle fluid load early after surgery.

Preservation of the right atrial appendage improves reduced plasma atrial natriuretic peptide levels after the maze procedure.

OBJECTIVES: The present study was conducted to determine whether preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and whether the increase of plasma atrial natriuretic peptides improves the ability of the kidneys to excrete the fluid load after the operation. METHODS: We evaluated 42 patients who underwent the maze procedure. The right atrial appendage was preserved in 22 patients but not in 20. Blood samples were obtained before and after the operation for measurement of atrial natriuretic peptides. To evaluate the influence of atrial natriuretic peptides on the ability of the kidneys, we also measured body weight, fluid balance, and the doses of furosemide and dopamine administered after the operation. RESULTS: The restoration to sinus rhythm at 1 month after was comparable in the two groups. Plasma atrial natriuretic peptide levels significantly increased after the operation in patients in whom the right atrial appendage was preserved (1 day after: 23.4 +/- 17.8 vs 3 days after: 42.7 +/- 23.6 and 7 days after: 36.3 +/- 23.7 pg/mL, P <.05) but not in patients in whom the right atrial appendage was not preserved (1 day after: 20.0 +/- 19.6, 3 days after: 28.5 +/- 19.3, and 7 days after: 23.0 +/- 16.1 pg/mL). Furthermore, plasma atrial natriuretic peptide levels were significantly lower in patients in whom the right atrial appendage was not preserved than in patients in whom the right atrial appendage was preserved at 3 and 7 days after the operation. The fluid balance during the first 7 days of the postoperative period was comparable in the two groups, although the total dose of dopamine used in the same period was significantly smaller in patients in whom the right atrial appendage was preserved than in patients in whom the right atrial appendage was not preserved (155.3 +/- 119.0 vs 244.9 +/- 129.0 microg/kg, P <.05). CONCLUSIONS: The present study showed that preservation of the right atrial appendage lessens the decrease of plasma atrial natriuretic peptide levels after the maze procedure and that increased plasma atrial natriuretic peptides may improve the ability of the kidneys to excrete the fluid load after the operation.

Left ventricular structural and functional characteristics in patients with renovascular hypertension, primary aldosteronism and essential hypertension.

To investigate the effect of different etiologies of hypertension on left ventricular structure and function, we compared echocardiographic findings in 10 patients with renovascular hypertension (35 +/- 9 years), 10 patients with primary aldosteronism (42 +/- 9 years), and 14 patients with essential hypertension (41 +/- 6 years). There were no significant differences among the three groups in age, sex, body surface area, blood pressure, interventricular septal thickness, posterior wall thickness, left ventricular end-diastolic dimension or end-systolic dimension, relative wall thickness, left ventricular mass index, or spectrum of left ventricular adaptation (concentric remodeling, concentric hypertrophy, or eccentric hypertrophy). There were no differences in systolic function or diastolic function, which was assessed in terms of the peak rate of increase in dimension normalized for left ventricular end-diastolic dimension (dD/dt/D), the relaxation time, and the relaxation time to peak velocity of lengthening among groups. Multiple regression analysis showed that the systolic blood pressure was the most important determinant of left ventricular mass index (r = 0.56, P < .01), and that left ventricular mass index was the most important determinant of relaxation time and the relaxation time to peak velocity of lengthening (r = 0.48, P < .01 and r = 0.59, P < .01, respectively). The dD/dt/D was correlated only with left ventricular end-systolic dimension (r = 0.59, P < .01). Our results suggest that blood pressure may be a strong determinant of left ventricular hypertrophy, irrespective of the etiology of hypertension, and that the degree of hypertrophy may be related to left ventricular diastolic dysfunction in hypertensive patients with normal systolic function.