Effect of spironolactone on cardiac sympathetic nerve activity and left ventricular remodeling in patients with dilated cardiomyopathy

OBJECTIVES: We sought to evaluate the effects of spironolactone on cardiac sympathetic nerve activity and left ventricular (LV) remodeling in patients with dilated cardiomyopathy (DCM). BACKGROUND: Aldosterone prevents the uptake of norepinephrine and promotes structural remodeling of the heart. Spironolactone, an aldosterone receptor blocker, improves LV remodeling in patients with DCM, but its influence on cardiac sympathetic nerve activity has not been determined. METHODS: We selected 30 patients with DCM who were treated with an angiotensin-converting enzyme inhibitor and a loop diuretic. Fifteen patients were assigned to receive spironolactone additionally, whereas the remaining 15 patients continued their current regimen. The delayed heart/mediastinum (H/M) count ratio, delayed total defect score (TDS), and washout rate (WR) were determined from iodine-123 ((123)I)-meta-iodobenzylguanidine (MIBG) images before and six months after treatment. The left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction (LVEF) were determined by echocardiography, and New York Heart Association (NYHA) functional class was estimated.RESULTS: In the spironolactone group, the TDS decreased from 36 +/- 9 to 24 +/- 13 (p < 0.0001), the H/M ratio increased from 1.64 +/- 0.20 to 1.86 +/- 0.27 (p < 0.0001), and WR decreased from 55 +/- 12% to 41 +/- 15% (p < 0.0005). In addition, the LVEDV decreased from 187 +/- 26 to 154 +/- 41 ml (p < 0.005), and LVEF increased from 33 +/- 6% to 39 +/- 6% (p < 0.005). However, there were no significant changes in these parameters in the control group. There was a significant correlation between changes in the (123)I-MIBG findings and changes in LVEDV with spironolactone treatment (TDS: r = 0.684, p = 0.0038; H/M ratio: r = -0.878, p < 0.0001; and WR: r = 0.737, p = 0.0011). The NYHA functional class improved in both groups but showed a greater improvement in the spironolactone group than in the control group (p < 0.01). CONCLUSIONS: Spironolactone improves cardiac sympathetic nerve activity and LV remodeling in patients with DCM.     

Relationship between firing activity of bombyxin-producing neurosecretory cells and hemolymph bombyxin titer in the silkworm Bombyx mori

Isolated brain-retrocerebral neurohemal complex of the silkworm of Bombyx mori was stimulated electrically and the released bombyxin (an insulin-like neuropeptide) was measured using time-resolved fluoroimmunoassay. The amount of bombyxin release depended on the number of stimulus pulses delivered to the axonal tract of the bombyxin-producing (BP) neurosecretory cells, and 17 fg of bombyxin per pulse was released from a cell. The titer of bombyxin in the hemolymph of bombyxin-II injected pupae decreased exponentially, the half-life being 170 min. To relate firing activity of a population of BP cells to the hormone titer in the hemolymph, bombyxin titer and its change in the hemolymph were calculated numerically. We assumed that the amount of bombyxin release was proportional to the firing rate of BP cells and the released bombyxin was inactivated with the same time course of injected bombyxin. Our calculations suggested that the hemolymph bombyxin titer may fluctuate dynamically and the mean titer is 380 pg/ml, a level which is close to the actually determined bombyxin titer at middle stages of pupal-adult development.     

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population

BackgroundThe current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (V?E) to the ramp exercise test in the normal Japanese population are not known.MethodsA total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and V?E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V?E versus carbon dioxide (V?CO₂) (V?E vs. V?CO₂ slope), minimum V?E/V?CO₂, and oxygen uptake efficiency slope (OUES) were determined.ResultsFor males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p < 0.001), peak V?E (V?Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V?E vs. V?CO₂ slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V?E/V?CO₂ was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V?Epeak decreased with age and increased with weight and height. The V?E vs. V?CO₂ slope and minimum V?E/V?CO₂ increased with age, while conversely, the OUES decreased with age.ConclusionsWe have established the normal range of VT and V?E responses, the V?E vs. V?CO₂ slope, the minimum V?E/V?CO₂, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.     

Clinical evaluation of rapid diagnostic kit detecting separately influenza A and B viruses

The Directigen Flu A + B kit, a rapid diagnostic device for influenza virus A and B was evaluated. The nasopharyngeal aspirates were obtained from 239 patients who visited our hospital, between January and March, 2000, presenting flu-like symptoms. Influenza virus AH1: 77 and AH3: 51 were isolated from 128 specimens and none from 111 specimens. Directigen Flu A + B showed 115 specimens positive and 106 specimens negative. The sensitivity and specificity of this kit were 89.8% (115/128) and 95.5% (106/111) compared with viral isolation. Agreement on positive and negative interpretations between Direction Flu A and this kit was 97.9% (234/239). In the evaluation of this kit for influenza B virus, 60 frozen nasopharyngeal aspirates collected from February to April, 1999 were used. The sensitivity and specificity of this kit were 88.9% (16/18) and 88.1% (37/42) compared with viral isolation. Agreement on positive and negative interpretations between FLU OIA and this kit was 91.7% (55/60). The Directigen A + B demonstrated sensitivity and specificity equivalent to the conventional kits in nasopharingeal aspirates. This kit can also differentiate influenza A and B viruses, a feature which is useful for treatment using anti-viral agents such as amantadine and neuraminidase inhibitor. To date, the kit is the most effective tool for the rapid diagnosis of influenza.     

Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity and left ventricular remodeling in patients with first anterior acute myocardial infarction.

OBJECTIVES: We sought to evaluate the effects of atrial natriuretic peptide (ANP) on cardiac sympathetic nerve activity (CSNA) and left ventricular (LV) remodeling in patients with first anterior acute myocardial infarction (AMI) after primary coronary angioplasty. BACKGROUND: The activation of the renin-angiotensin-aldosterone system (RAAS) prevents the uptake of norepinephrine in the myocardium. Atrial natriuretic peptide, a circulating hormone of cardiac origin, has vasodilatory and diuretic properties, and can inhibit the RAAS. METHODS: We studied 50 patients with first anterior AMI who were randomly assigned to receive ANP (group A) or isosorbide dinitrate (group B) before and after primary coronary angioplasty. The ANP or ISDN was continuously infused >48 h. The extent score (ES) was determined from 99mTc-pyrophosphate scintigraphy to evaluate the area of initial myocardial damage 3 to 5 days after primary angioplasty. The LV end-diastolic volume (LVEDV) and LV ejection fraction (LVEF) were determined by left ventriculography 2 weeks later. The delayed heart/mediastinum count (H/M) ratio, delayed total defect score (TDS), and washout rate (WR) were determined from 123I-meta-iodobenzylguanidine scintigraphy after 3 weeks. RESULTS: After primary angioplasty, age, gender, risk factors, peak serum creatine phosphokinase concentration, recanalization time, and ES were similar in the 2 groups. However, in group A (n = 25), the TDS was significantly lower (34 +/- 8 vs. 41 +/- 8; p < 0.05), the H/M ratio was significantly higher (1.96 +/- 0.18 vs. 1.74 +/- 0.23; p < 0.05), and the WR was significantly lower (35 +/- 8% vs. 44 +/- 12%; p < 0.005) than in group B (n = 25). Moreover, the LVEDV and LVEF in group A were better than in group B (LVEDV: 85.5 +/- 28.5 ml vs. 106.3 +/- 39.4 ml [p < 0.05]; LVEF: 47.9 +/- 10.2% vs. 41.5 +/- 11.8% [p < 0.05]). CONCLUSIONS: Intravenous ANP improves CSNA and prevents LV remodeling in patients with first anterior AMI.     

Host factors which influence the outcome of pneumonia in the elderly]

We examined 135 elderly patients with pneumonia to clarify the factors predicting on the outcomes of the elderly pneumonic patients. In the fatal cases respiratory symptoms such as cough and sputum, except for dyspnea were less frequent but pulmonary infiltrations on chest roentgenograms were more massive as compared with those in the survived cases. Thus, it was suggested that in the fatal cases the more advanced pneumonia had developed at the time when the diagnosis of pneumonia was made. The fatal cases showed hypoalbuminemia, hypocholesterolemia and hyponatlemia more frequently as compared with survived cases. Among these laboratory values, the decreased serum albumin concentration seemed to be most closely correlated with the fatal outcome of the elderly pneumonic patients. There were significant differences in the outcomes among three groups of the patients, those who were the prolonged bed-ridden, those with severe underlying diseases such as cancer and those treated as out-patients. The out patients showed the most favorable outcome and the prolonged bed-ridden patients the worst outcome. Approximately, 39% of the fatal cases were complicated with multiple organ failure. These results suggest that more important factors which affect the outcomes of pneumonia in the elderly may be not merely aging but the conditions of the host at onset of the disease.     

Angiotensin II plays an important role in maintaining blood pressure in postmenopausal women receiving hormone replacement therapy

BACKGROUND: We investigated the role of angiotensin (Ang) II in maintaining blood pressure (BP) by administering a small dose of candesartan, an Ang II type 1 receptor antagonist, in postmenopausal women receiving long-term hormone replacement therapy (HRT). METHODS: A single dose of 2 mg of candesartan was administered orally to 13 normotensive postmenopausal women receiving HRT (continuous combined conjugated estrogen and medroxyprogesterone acetate orally; HRT group) and 13 normotensive postmenopausal women not receiving HRT (control group). Both BP and heart rate (HR) were measured at baseline and at 1, 2, 3, 4, 5, and 6 h after administration. Plasma renin activity (PRA) and Ang I, Ang II, and bradykinin concentrations were measured at baseline and 4 h after the administration of candesartan. RESULTS: Candesartan lowered the BP and raised the HR in both groups. However, the decrease in BP was significantly greater in the HRT group than in the control group (P < .05), whereas no significant difference in the change in HR was observed between the two groups. In the HRT group, significant increases were found in PRA, Ang I, and Ang II (all P < .05) and a significant decrease in bradykinin (P < .01) with candesartan treatment. In the control group, candesartan as associated with an increase in PRA (P < .05) but not in Ang I, Ang II, or bradykinin. CONCLUSIONS: Based on our study results, Ang II plays an important role in maintaining BP in normotensive postmenopausal women receiving HRT. Maintenance of BP may be dependent on the balance between the hypertensive effect of Ang II and the hypotensive effect of bradykinin.