[Arrhythmias newly provoked by exercise training in patients who underwent cardiac surgery].

We investigated the incidence and the varieties of arrhythmia during exercise training in patients who underwent cardiac surgery. Subjects were 1293 patients who underwent cardiac surgery and enrolled our cardiac rehabilitation program. According to the charts and cardiac rehabilitation records, we evaluated the incidence and the varieties of arrhythmia provoked by exercise training in patients after cardiac surgery retrospectively. The arrhythmias related to the exercise training were provoked in 12 times, and the incidence was only 0.09% (12/13646). Atrial fibrillation was the most common arrhythmia, and the incidence was 41.6% (5/12) in these patients. Moreover, these arrhythmias occurred within 2 weeks after surgery. Although most patients recovered to the sinus rhythm spontaneously, 3 patients needed medical treatment or cardioversion. We concluded that the arrhythmia provoked by exercise training in patients after cardiac surgery were rare, non-fatal, and common in the early recovery phase after surgery. However, the supervised exercise training was required in those patients, particularly in early recovery phase of cardiac surgery.

Value of plasma B type natriuretic peptide measurement for heart disease screening in a Japanese population.

BACKGROUND: Conflict exists regarding the usefulness of measuring plasma B type natriuretic peptide (BNP) concentrations for identifying impaired left ventricular (LV) systolic function during mass screening. Various cardiac abnormalities, regardless of degree of LV dysfunction, are prone to carry a high risk of cardiovascular events. OBJECTIVE: To examine the validity of plasma BNP measurement for detection of various cardiac abnormalities in a population with a low prevalence of coronary heart disease and LV systolic dysfunction. DESIGN AND SETTING: Participants in this cross sectional study attended a health screening programme in Iwate, northern Japan. Plasma BNP concentrations were determined in 1098 consecutive subjects (mean age 56 years) by direct radioimmunoassay. All subjects underwent multiphasic health checkups including physical examination, ECG, chest radiography, and transthoracic echocardiography. RESULTS: Conventional diagnostic methods showed 39 subjects to have a wide range of cardiac abnormalities: lone atrial fibrillation or flutter in 11; previous myocardial infarction in seven; valvar heart disease in seven; hypertensive heart disease in six; cardiomyopathy in six; atrial septal defect in one; and cor pulmonale in one. No subjects had a low LV ejection fraction (< 40%). To assess the utility of plasma BNP measurement for identification of such patients, receiver operating characteristic analysis was performed. The optimal threshold for identification was a BNP concentration of 50 pg/ml with sensitivity of 89.7% and specificity of 95.7%. The area under the receiver operating characteristic curve was 0.970. The positive and negative predictive values at the cutoff level were 44.3% and 99.6%, respectively. CONCLUSION: Measurement of plasma BNP concentration is a very efficient and cost effective mass screening technique for identifying patients with various cardiac abnormalities regardless of aetiology and degree of LV systolic dysfunction that can potentially develop into obvious heart failure and carry a high risk of a cardiovascular event.

Effect of age on renal functional and orthostatic vascular response in healthy men.

1. Few studies have been reported concerning the effect of ageing on renal functional and vascular responses to various stresses during ordinary life. In the present study, we examined the effect of age on changes in renal sodium handling and renal vascular resistance (RVR) in response to standing from a supine position in subjects with normal renal function. 2. We selected 43 healthy males in the second through to the seventh decade of life and gave them a constant dietary sodium intake before the study period. Renal function was estimated by standard clearance methods with the subject in a state of euvolaemia. 3. The mean daily urinary excretion of sodium was 236 +/- 22 mEq. Standing from a supine position was associated with significant decreases (P < 0.0001) in creatinine clearance (from 125 +/- 18 to 117 +/- 19 mL/min per 1.73 m2), sodium excretion (from 178 +/- 29 to 97 +/- 23 microEq/min) and fractional excretion of sodium (from 1.02 +/- 0.19 to 0.60 +/- 0.13%). A significant increase (P < 0.0001) in the RVR index (from 0.11 +/- 0.03 to 0.14 +/- 0.04 units) was noted. Univariate analysis indicated that while the change in RVR associated with standing was significantly diminished (P < 0.05) in older subjects, orthostatic changes in other parameters associated with standing were minimally influenced by age. 4. In conclusion, although the renal vascular response is impaired in advanced age, the renal functional response to orthostasis is otherwise maintained in healthy elderly subjects under conditions of normal sodium intake and clinical euvolaemia.

Usefulness of carperitide for the treatment of refractory heart failure due to severe acute myocardial infarction.

Carperitide (synthetic atrial natriuretic peptide) is a newly developed drug for the treatment of heart failure. Although this drug has been used for various types of heart failure, it remains unknown whether it has additive effects on hemodynamic parameters or renal excretory function during intensive treatment for acute refractory heart failure. We have examined the cardiorenal and hormonal effects of carperitide (0.05-0.10 microg / min / kg) in 9 patients (mean age: 67+/-8 years) with severe heart failure complicated with acute myocardial infarction, in which a range of intensive treatments have already been started. Hemodynamic parameters were determined before and 4, 24 and 48 hours after initiation of carperitide. Pulmonary capillary wedge pressure (mean+/-SD) had decreased dramatically from 21+/-6 to 11+/-5 mmHg (p<0.01) 4 hours after the treatment without significant renal effects. Heart rate and systemic blood pressure were not significantly changed. These beneficial effects were maintained for at least 24 hours. Plasma aldosterone levels fell significantly in response to the drug (from 148+/-68 to 56+/-29 pg / ml; p<0.05). However, mean hourly urine output remained unchanged after carperitide. In conclusion, intravenous infusion of carperitide promptly and persistently reduces left ventricular filling pressure without diuresis, hypotension, reflex tachycardia, or neurohormonal activation in patients with refractory heart failure due to severe acute myocardial infarction.

Transient spontaneous regression of aggressive non-Hodgkin's lymphoma confined to the adrenal glands.

A 72-year-old-man with night sweats and a low-grade fever was found to have bilateral adrenal enlargement associated with incipient adrenal insufficiency. Without any intervention, these adrenal lesions regressed spontaneously, accompanied by disappearance of clinical symptoms. Seven months later, however, the lesions became enlarged and exceeded their initial size while remaining confined to the adrenals, associated with reappearance of nights sweats and overt adrenal insufficiency. Upon unilateral laparoscopic adrenalectomy, the lesion proved histopathologically to be diffuse large B cell non-Hodgkin's lymphoma (NHL). After contralateral laparoscopic adrenalectomy and adjuvant chemotherapy, the patient remains alive with no recurrence at 26 months. Treatment with bilateral adrenalectomy and chemotherapy is effective for aggressive NHL confined to bilateral adrenal glands. A transient clinical improvement without treatment was considered to be due to a spontaneous regression of NHL, although we could not confirm the histological results before the regression. Such tumor behavior showing spontaneous regression in spite of aggressive histology may also be related to the favorable outcome, even though regression was transient.

46, XY pure gonadal dysgenesis: a case with Graves' disease and exceptionally tall stature.

A case of 46, XY pure gonadal dysgenesis with very tall stature was investigated. The 24-year-old, phenotypically female patient consulted our clinic because of linear growth persisting into adulthood. The patient was found to have no mutation or deletion of a sex-determining region of the Y chromosome, and also was found to have Graves' disease. Growth was arrested with height remaining at 187 cm after normalization of the thyroid function by treatment with an antithyroid agent, although follow-up to monitor growth was limited to 3 months. In some cases of gonadal dysgenesis, then, Graves' disease may contribute to an abnormally tall stature.

Brain natriuretic peptide and cardiac rupture after acute myocardial infarction.

Cardiac rupture is a fatal complication in the acute stage of myocardial infarction (MI). However, no measures have yet been established to predict it. Herein we describe three MI patients with cardiac rupture in whom plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations had been serially monitored from the onset of MI to cardiac rupture. In these cases, plasma BNP levels increased without symptomatic and hemodynamic changes and reached their highest level immediately before cardiac rupture, while plasma ANP levels remained unchanged. These cases suggest that the increased plasma BNP concentrations without symptomatic and hemodynamic changes may be a useful marker for predicting cardiac rupture after acute MI.

Successful steroid therapy for cefdinir-induced acute tubulointerstitial nephritis with progressive renal failure.

A 58-year-old woman was admitted to our hospital because of renal dysfunction that continued to progress even after withdrawal of cefdinir, the presumed cause of acute renal failure. Renal histologic findings included interstitial fibrosis accompanied by moderate lymphocytic infiltration, and tubular atrophy with reduced numbers of epithelial cells. Mesangial cells and glomerular basement membranes were nearly normal. Scintigraphy with 67gallium disclosed diffuse abnormal accumulation in both kidneys. A lymphocyte stimulation test with cefdinir was positive. The patient was diagnosed with acute tubulointerstitial nephritis caused by cefdinir. Serum creatinine concentrations continued to rise after withdrawal of the drug, but steroid therapy was effective in normalizing renal function.

Blunted peripheral vasodilatory response is a hallmark of progressive deterioration in mild to moderate congestive heart failure.

BACKGROUND: Several reports have shown that dilatory response to acetylcholine (ACh) and nitroprusside (SNP) is blunted in the limb vasculature in patients with congestive heart failure (CHF). However, it is not yet known whether this vascular dysfunction is related to clinical outcome. We have examined the relationship between peripheral vasodilatory response and prognosis of CHF. METHODS AND RESULTS: A total of 46 patients with mild to moderate CHF were enrolled (mean age 56 years). Changes in forearm blood flow (FBF) during intra-arterial infusion of ACh and SNP were determined by plethysmography. FBF changes above baseline for each dose were cumulated and used as an index of endothelium-dependent (ACh) response and endothelium-independent (SNP) response, respectively. During the follow-up period (mean 32 months), 9 patients were admitted to the hospital for treatment of worsening refractory CHF, and 6 patients died suddenly or developed life-threatening arrhythmia. By Kaplan-Meier analysis, when all cardiac events were included, no significant differences were observed between any levels of vascular response in terms of prognosis. However, when deterioration events were analyzed separately, patients with SNP responses below the median (7.4 mL/min/dL) had significantly higher rates of hospital admission caused by worsening CHF than those with above the median responses (P <.05). This relationship was not found between ACh response and clinical outcome. By Cox multivariate analysis, blunted vasodilatory response to SNP was a significant predictor of worsening CHF (chi(2) = 3.95; P <.05). CONCLUSION: This study has shown that patients with mild to moderate CHF showing a blunted vascular response to SNP rather than ACh were admitted to the hospital more frequently because of deterioration of CHF. This finding suggests that changes in vascular smooth muscle and/or vascular structure in the peripheral vasculature may be a critical element in the worsening of CHF.

Body height is a determinant of seasonal blood pressure variation in patients with essential hypertension.

To determine the factors that affect seasonal variation in blood pressure (BP) in a fairly large number of patients with essential hypertension who stayed almost entirely indoors in a stable environmental temperature and who took a calcium channel blocker during the study. This prospective study of hypertensive patients was conducted during the summer and winter. BP was measured by ambulatory blood pressure monitoring; the indoor temperature was measured at the time of the BP measurement using an electrothermometer with the subject awake and indoors. Subjects comprised 38 men and 57 women. The subjects spent virtually the entire day indoors during both the summer (men, 22.1+/-1.6 h; women, 23.0+/-0.9 h) and winter (men, 23.0+/-0.9 h; women, 22.9+/-0.9 h). During the waking hours, the systolic/diastolic BPs were significantly higher during the winter than the summer. The differences were 8+/-9/4+/-5 mmHg in men and 5+/-11/2+/-6 mmHg in women; these values were not significantly different between men and women. No significant seasonal differences in BP during the sleeping hours were noted. There was a significant difference of approximately 6 degrees C in the environmental temperature during waking hours, but there was no significant difference in urinary excretion of sodium or in exercise activity between the seasons. Only body height was significantly correlated with the winter increase in waking BP in both men and women, even after adjustment for potential confounding variables. Body height was a determinant of the increase in waking BP during the winter in hypertensive patients who lived almost entirely indoors.

What determines the heart rate response to exercise in patients with atrial fibrillation?

We evaluated the factors that determine the heart rate response to exercise in 60 patients with atrial fibrillation (25 men and 35 women, with a mean age of 61+/-10 years) who underwent symptom limited cardiopulmonary exercise testing with blood sampling of atrial natriuretic peptide (ANP), 2-dimensional echocardiography and cardiac catheterization. Atrial muscles resected during the Maze operation were examined histologically in 12 patients. The heart rate response to exercise depended on the severity of the atrial organic injury, which was expressed as left atrial diameter, ANP secretion during the maximal exercise testing and the histological findings of atrial tissue. Conversely, we believe that the severity of the atrial injury can be predicted from the heart rate response to exercise in patients with atrial fibrillation.

Marked and prompt hemodynamic improvement by carperitide in refractory congestive heart failure due to dilated cardiomyopathy.

A 16-year-old Japanese male diagnosed with congestive heart failure (CHF) due to dilated cardiomyopathy was treated by conventional intensive treatment such as intravenous infusion of diuretics, catecholamines, and phosphodiesterase inhibitors with vasodilators. However, he developed a low output syndrome with appearances of hyponatremia and hypochloremia. As a consequence, intravenous infusion of carperitide (synthetic atrial natriuretic peptide) was added to the therapy. Thereafter his symptoms and hemodynamic parameters promptly and dramatically improved without significant diuresis, and this amelioration persisted for more than 20 days without drug intolerance. This outcome suggests that use of carperitide may be a safe and efficacious means to reduce cardiac preload without hypotension and tachycardia in patients with refractory CHF in whom intensive treatment has already been performed.

Effects of tumor necrosis factor-alpha on basal and stimulated endothelium-dependent vasomotion in human resistance vessel.

The aim of this study was to determine whether tumor necrosis factor (TNF)-alpha would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low-dose intraarterial forearm infusion of TNF-alpha according to the following three protocols in healthy volunteers. In the condition without pretreatment, basal FVR was significantly increased by TNF-alpha (from 30.5 +/- 4.8 to 39.9 +/- 5.9 units; p < 0.01), whereas ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid, although the vascular effects of TNF-alpha on basal FVR appeared to be blocked (37.1 +/- 5.3 vs. 37.6 +/- 5.2; NS), ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine, the vascular effect of TNF-alpha on basal FVR was diminished, and the ACh-induced maximal dilatory response was significantly blunted after TNF-alpha compared with before TNF-alpha (minimal FVR: 30.4 +/- 12.0 vs. 12.3 +/- 4.2 units; p < 0.05). These findings suggest that brief exposure of the human forearm resistance artery to TNF-alpha may increase basal bioavailability of the vasoconstrictor prostaglandin and reduce basal bioavailability of NO. In the stimulated condition, TNF-alpha-induced vascular dysfunction may be overwhelmed by increased NO bioavailability in healthy humans.

Diagnostic implications of elevated levels of smooth-muscle myosin heavy-chain protein in acute aortic dissection. The smooth muscle myosin heavy chain study.

BACKGROUND: A rapid 30-minute assay of circulating smooth-muscle myosin heavy-chain protein has been developed as a biochemical diagnostic tool for aortic dissection. OBJECTIVE: To determine the sensitivity and specificity of this assay. DESIGN: Cross-sectional study. SETTING: 8 major cardiovascular centers in Japan. PATIENTS: 95 patients with acute aortic dissection, 48 patients with acute myocardial infarction, and 131 healthy volunteers. MEASUREMENTS: Levels of circulating smooth-muscle myosin heavy-chain protein. RESULTS: Patients with acute aortic dissection who presented within 3 hours after onset had elevated levels of circulating smooth-muscle myosin heavy-chain protein. In these patients, the assay had a sensitivity of 90.9%, a specificity of 98% compared with healthy volunteers, and a specificity of 83% compared with patients who had acute myocardial infarction; the clinical decision limit was 2.5 microgram/L. All patients with proximal lesions had elevated levels of smooth-muscle myosin heavy-chain protein, and only patients with distal lesions had decreased levels (<2.5 microgram/L). CONCLUSIONS: Levels of smooth-muscle myosin heavy-chain protein can be used to diagnose aortic dissection soon after symptom onset. The assay had the greatest diagnostic value in patients with proximal lesions.

Expression of tumor necrosis factor-alpha--converting enzyme and tumor necrosis factor-alpha in human myocarditis.

OBJECTIVES: We determined whether tumor necrosis factor-alpha-converting enzyme (TACE) is expressed with tumor necrosis factor-alpha (TNF-alpha) in myocarditis. BACKGROUND: Tumor necrosis factor-alpha-converting enzyme, which has recently been identified as belonging to the family of metalloproteinase disintegrin proteins, is responsible for the conversion of TNF-alpha precursor to its mature form. METHODS: We examined TACE and TNF-alpha expressions in endomyocardial biopsy tissues obtained from 14 patients with myocarditis and five control subjects by using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. RESULTS: Expression of TNF-alpha and TACE messenger ribonucleic acid (mRNA) was significantly greater in the myocarditis group than in the control group. A positive correlation was found between TNF-alpha and TACE mRNAs (r = 0.83, p < 0.05). Six patients with severe myocarditis underwent repeat biopsies. Although TNF-alpha and TACE mRNAs were expressed at high levels in the initial biopsies, a marked decrease was noted in the repeat biopsies. The immunostainings for TNF-alpha and TACE were positive in the myocytes and interstitial cells of myocardium obtained from patients with myocarditis. Expression of TACE and TNF-alpha mRNAs was greater in the subgroup in New York Heart Association functional class III or IV than in the subgroup in class I or II. Expression of TACE and TNF-alpha mRNA was correlated positively with left ventricular volume (TNF-alpha: r = 0.85; TACE: r = 0.80) and negatively with left ventricular systolic function (TNF-alpha: r = -0.85; TACE: r = -0.85). CONCLUSIONS: These findings indicate that the expression of TNF-alpha and TACE may have important implications in the pathogenesis of myocarditis and may influence advanced cardiac dysfunction in myocarditis.

Dilation and reduced distensibility of carotid artery in patients with abdominal aortic aneurysms.

BACKGROUND: Although patients with abdominal aortic aneurysms (AAA) frequently have coexisting systemic atherosclerosis, the dilatative manifestation of AAA is the opposite of the occlusion characteristic of atherosclerotic disease. It has been suggested that this dilatative disease is caused by an alteration in connective tissue metabolism in systemic arterial wall. Such a condition might alter systemic arterial diameter and wall behavior. We investigated arterial characteristics in AAA patients, including morphologic changes and wall mechanics in the carotid artery. METHODS AND RESULTS: Atherosclerotic intimal changes such as intima-media thickness (IMT), plaque formation, diameter, and wall elasticity of the carotid artery were determined ultrasonographically in patients with AAA (n = 102) and compared with age-matched patients with the atherosclerotic diseases arteriosclerosis obliterans (ASO, n = 115) and coronary artery disease (CAD, n = 123) and with age-matched healthy control patients (CTL, n = 45). Intimal disease in AAA was significantly milder than in ASO, at the same level as CAD, and more severe than in CTL. Although end-diastolic luminal diameters (mm) in AAA (7.05 +/- 1.08), ASO (6.74 +/- 0.18), and CAD (6.66 +/- 0.83) were significantly higher than in CTL (5.97 +/- 0.93), they were also excessively increased compared with the equivalent diameters seen in ASO (P <.01) and CAD (P <.01). Luminal distensibility (x 10(-6) cm(2). dyne(-1)) in AAA (0.83 +/- 0.48) was excessively decreased compared not only with CTL (1.70 +/- 1.11, P <.01) but also with ASO (1.12 +/- 0.47, P <.01) and CAD (1.18 +/- 0.59, P <. 01). These relations remained true when adjusted for blood pressure and luminal diameter. Intra-AAA group analysis showed that distensibility in ruptured cases (n = 14) was significantly lower than in nonruptured cases (n = 88) (0.58 +/- 0.24 vs 0.88 +/- 0.50, P <.05). CONCLUSIONS: Excessive arterial dilation and reduced distensibility without severe intimal disease were found in the carotid arteries of patients with AAA. This suggests that these patients may be subject to systemic arterial alterations, including structural and functional abnormalities.

[The effects of aerobic training on the emotional response in patients who underwent cardiac surgery].

It has been reported that cardiac surgery and aerobic training influence the patient's emotional response. We investigated the changes in emotional response before and after cardiac surgery and during aerobic exercise training as a cardiac rehabilitation using profile of mood states (POMS). Subjects were thirty-five patients (25 men and 10 women, average 57 years) who underwent cardiac surgery. All patients participated in the rehabilitation program which included aerobic exercise training after cardiac surgery. Aerobic training consisted of cycle ergometer or treadmill. Emotional states were evaluated by POMS score at the preoperative phase, early postoperative phase (about 10 days after surgery) and aerobic training (about 20 days after surgery). Most of the emotional state (tension, anxiety, anger and hostility) significantly improved after cardiac surgery. In particular, aerobic training has an additional effect for improving one of the emotional state which is tension and anxiety. However, several factors such as deconditioning, postoperative complications and high age delayed the improving of emotional response.

Circulating biochemical marker levels of collagen metabolism are abnormal in patients with abdominal aortic aneurysm.

Changes in extracellular matrix composition induced by abnormal collagen metabolism in the aortic wall may be an important factor in the progression of aortic structural changes. The authors have measured several types of biochemical marker for collagen metabolism in plasma: carboxyterminal propeptide of type Icollagen (PICP) for a pure collagen synthesis marker, matrix metalloproteinase-1 (MMP-1) for a degradation marker of collagen matrix, and tissue inhibitors of metalloproteinase-1 (TIMP-1) as a native inhibitor of MMP-1. Subjects of this study were 17 patients with abdominal aortic aneurysm (AAA), 14 patients with atherosclerosis obliterans (ASO), and 22 age/sex-matched healthy controls (HC). Blood samples were drawn from a forearm vein and measured by radioimmunoassay or enzyme-linked immunosorbent assay. Plasma concentrations of PICP in patients with AAA were significantly decreased compared to those in HC patients (82.0 +/- 16.4 vs 111.3 +/- 40.3 ng/mL; p < 0.01), but those in patients with ASO (105.4 +/- 55.4 ng/mL) were comparable to control concentrations. Although no differences in plasma concentrations of MMP-1 were observed among the three subject groups (HC, 20.0 +/- 5.6 ng/mL; ASO, 21.4 +/- 13.8 ng/mL; AAA, 24.5 +/- 11.7 ng/mL; NS), MMP-1/PICP ratio as an index of collagen degradation to collagen neosynthesis in AAA was significantly elevated compared to HC (0.32 +/- 0.18 vs 0.20 +/- 0.08; p < 0.01). Plasma concentrations of TIMP-1 in patients with AAA (293.8 +/- 61.2 ng/mL) or ASO (327.6 +/- 54.9 ng/mL) were significantly higher than in HC (227.3 +/- 60.2 ng/mL; both p < 0.01). In conclusion, these data suggest that although a compensatory mechanism such as increased TIMP-1 may be activated, collagen neosynthesis may decrease with relatively increased collagen degradation in patients with AAA.