Gastroesophageal reflux during enteral feeding in stroke patients: a 24-hour esophageal pH-monitoring study.

BACKGROUND: Patients who are unable to eat or drink after stroke may receive percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Although the most common serious complication is well known to be aspiration pneumonia, the role of gastroesophageal reflux (GER) has not been fully assessed. The aim of this study was to examine, by means of 24-hour esophageal pH monitoring, whether GER is related to aspiration pneumonia and whether the size and laterality of brain lesions influence GER. METHODS: Sixteen stroke patients were examined using a Degitrapper pH400 (Medtronic Japan Co., Tokyo, Japan) and Zinetics 24ME multiuse pH catheter (Medtronic). All patients had stroke lesions in the territory of the left or right middle cerebral artery that were confirmed by magnetic resonance imaging (MRI) and were receiving PEG or nasogastric feeding. Stroke volume was measured with MRIcron software. RESULTS: Nine patients (56%) were diagnosed with GER, and 10 (63%) developed aspiration pneumonia after enteral feeding. The rate of aspiration pneumonia was significantly higher in patients with GER (88.9%) than in those without GER (42.9%; P = .04). Patients with left hemispheric lesions had a significantly higher incidence of acid reflex than those with right lesions (116 ± 105 vs 13 ± 17; P = .04). There were no significant differences in total time of acid reflux or mean pH value between patients with left and right hemispheric lesions. The lesion volume had no significant effect on any of 3 indices of GER. CONCLUSIONS: GER is associated with aspiration pneumonia and occurs more often in patients with stroke lesions in the left hemisphere.

Steroid-induced crisis and rhabdomyolysis in a patient with pheochromocytoma: a case report and review.

A 66-year-old Japanese woman was urgently referred to our hospital. Two days prior to admission, her general practitioner began to administer prednisolone for treatment of a diagnosis of polymyalgia rheumatica. At the time of admission, laboratory results indicated multiorgan failure with rhabdomyolysis. Abdominal ultrasonography and computed tomography revealed a tumor in the right adrenal gland. On the same day, we measured serum and urine cathecholamines, which were markedly elevated. Additionally, magnetic resonance imaging revealed an adrenal mass and metaiodobenzylguanidine scintigraphy showed labeling of the tumor. Then, the patient underwent surgical resection of the tumor via laparoscopy. Histological examination confirmed the diagnosis of pheochromocytoma. One week after the operation, serum and urinary catecholamine levels returned to normal. The patient was discharged 10 days after the operation, and has remained stable at home. This report indicates that steroid should be avoided if possible in patients with pheochromocytoma. Furthermore, pheochromocytoma should be recalled as a differential diagnosis whenever patients take a sudden turn for the worse, or have acute uncontrollable hypertension following steroid administration and/or whenever patients present with unexplained rhabdomyolysis.

The pitfall of coagulase-negative staphylococci: a case of Staphylococcus lugdunensis endocarditis.

We report a case of a 60-year-old woman. She was transferred from a local hospital to our cardiovascular medicine department with a diagnosis of infectious endocarditis due to Staphylococcus lugdunensis. Transthoracic echocardiograph confirmed the presence of large vegetations on the native aortic and mitral valve, and subsequent severe regurgitation due to the aortic and mitral valve destruction. Emergent operation was performed and patient's life was barely rescued. However, S. lugdunensis belongs to coagulase-negative staphylococci, which are generally regarded as relatively avirulent bacterium, the endocarditis caused by S. lugdunensis can be invasive and often resembles endocarditis due to Staphylococcus aureus. Therefore, whenever this organism is found in patients with endocarditis, early surgical treatment of the infected valve should be considered.

Activation of inducible NOS in peripheral vessels and outcomes in heart failure patients.

BACKGROUND: Activation of inducible nitric oxide synthase (iNOS) has been reported in congestive heart failure (CHF) conditions. However, it is unknown whether activation of iNOS affects prognosis of CHF patients. We prospectively studied the influence of activation of iNOS in the forearm on the outcome of CHF patients. METHODS AND RESULTS: Forearm blood flow (FBF) responses to 3 doses of acetylcholine (ACh) and nitroglycerin (NTG), and 4 doses of a selective iNOS inhibitor (aminoguanidine: Amn) and a nonselective NOS inhibitor (L-NMMA) were examined using plethysmography in 68 patients with CHF from idiopathic dilated cardiomyopathy. Plasma brain natriuretic peptide (BNP) and tumor necrosis factor-alpha (TNF-alpha) were also measured in all patients. During the mean follow-up period of 3.8 years, 25 patients were hospitalized for worsening heart failure and 9 of these patients died. Patients with adverse events had a diminished vasodilator response to ACh (P < .001) compared to patients without adverse events. Amn significantly decreased FBF (P < .001) in patients with adverse events, but not in patients without adverse events. FBF responses to NTG and L-NMMA were not significantly different between the 2 groups. When grouped by maximum FBF responses to each drug above and below the median value, multivariate Cox proportional hazards model analyses for cardiac event showed a significance in the FBF response to Amn (adjusted hazard ratio 5.89, P < .001). FBF responses to maximum dose of Amn significantly correlated with BNP and TNF-alpha levels (both P < .001). CONCLUSIONS: CHF patients with vascular iNOS activation, as demonstrated by a greater vasoconstrictor response to Amn, had poor outcomes. Activation of iNOS in peripheral vessels, associated with proinflammatory cytokines in accordance to the severity of heart failure, is a marker for, or contributes to, adverse events in patients with CHF.

Hepatitis C virus infection as a risk factor for increased aortic stiffness and cardiovascular events in dialysis patients.

BACKGROUND: Although links have been found between microorganisms and cardiovascular diseases, the role of hepatitis C virus (HCV) infection in the pathogenesis of arteriosclerosis and cardiovascular events is unclear. The primary objective of this research was to examine whether HCV infection is associated with increased aortic stiffness and cardiovascular events in chronic hemodialysis patients. SUBJECTS AND METHODS: A prospective cohort study was conducted in 94 dialysis outpatients from October 2002 to October 2004. Measurements included carotid-femoral pulse wave velocity (PWV), echocardiographic parameters, serum HCV-RNA (positive in 17 patients), and several items of biochemical data. Multiple logistic regression and the Cox proportional hazard model were used to assess independent determinants of high aortic PWV (> or =10.0 m/sec, mean) and cardiovascular events (including cerebral and peripheral vascular events), adjusting for several risk factors and duration of dialysis. RESULTS: The HCV-positive group had higher aortic PWV and lower serum cholesterol levels. Multivariate analysis indicated mean blood pressure, hemoglobin A1c and HCV viremia to be independent determinants of high PWV. During the follow-up period, 13 patients suffered from cardiovascular events. Prevalence of the diseases at baseline, pulse pressure, left ventricular mass index, HCV viremia and aortic PWV were associated with cardiovascular events. The Kaplan-Meier analysis indicated a significant difference in event-free rates between HCV-positive and HCV-negative patients. CONCLUSION: HCV infection is closely associated with increased aortic stiffness and cardiovascular event in dialysis patients.

Effects of long-term nicorandil administration on endothelial function, inflammation, and oxidative stress in patients without coronary artery disease.

Long-term administration of nicorandil has been shown to improve outcomes through cardioprotective effects in patients with coronary artery disease. To identify the mechanisms responsible for these effects, this study examined the impact of long-term nicorandil administration on endothelial function, systemic inflammatory markers, and oxidative stress in patients with cardiovascular risk factors. Fifty-three patients were assigned to receive either nicorandil therapy (15 mg/day; n = 26) (nicorandil group) or usual care (n = 27) (nonnicorandil group). All study participants underwent flow-mediated vasodilatation (FMD) of the brachial artery 1 month before treatment, just before treatment, and at 3, 6, and 12 months following treatment. At identical time points, serum levels of malondialdehyde-modified low-density lipoprotein (MDA-LDL) and high-sensitivity C-reactive protein (hs-CRP) were collected. Compared with the nonnicorandil group, the nicorandil group demonstrated significantly increased FMD at 12 months, a finding not replicated for endothelium-independent vasodilatation with nitroglycerine. Analysis of biochemical markers revealed significantly reduced MAD-LDL levels in the nicorandil group at 12 months, as compared to slightly increased MAD-LDL levels in the nonnicorandil group. Significant reductions in hs-CRP levels were also noted at 6 and 12 months in the nicorandil group, while no change was found in the nonnicorandil group. Results demonstrated that long-term nicorandil therapy is associated with gradual improvements in endothelial function. Our findings also suggest that nicorandil treatment may result in cardiovascular protection through pleiotropic effects including reductions in oxidative injury and systemic inflammation.

Transient elevation of serum tumor markers in a patient with hypothyroidism.

We report a case of a 66-year-old woman admitted to our hospital for examination and treatment of uterine and rectal prolapse, pleural and pericardial effusion, and ascites. On further examination, she was diagnosed with hypothyroidism. Test results showed markedly elevated concentrations of serum carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125). We consequently performed multiple imaging studies, none of which detected a malignancy. Hormonal replacement therapy with levothyroxine was started, and the pleural and pericardial effusion and ascites gradually abated. Concentrations of serum CEA and CA125 also decreased gradually after therapy with levothyroxine. These findings indicate that in patients with hypothyroidism, elevated CEA and CA125 levels do not necessarily indicate malignancy. Conversely, in any patient with elevated serum CEA and/or CA125, hypothyroidism should be considered in the differential diagnosis.

Cardiac involvement in Kugelberg-Welander disease: a case report and review.

There are few reports of cardiac involvement in patients with Kugelberg-Welander disease. We report a case of a 51-year-old man with Kugelberg-Welander disease who presented with syncope. His electrocardiogram showed complete right bundle branch block and transient complete atrioventricular block without escape rhythm. He was successfully treated with emergency temporary pacing followed by permanent pacemaker implantation. In this report, we review the relevant literature and argue that patients with Kugelberg-Welander disease should be evaluated regularly for cardiac disease.

[Effect of sarpogrelate in enteral feeding of patients with gastroesophageal reflux (GER)].

AIM: Enteral feeding of patients who are unable to eat or drink because of neurological disorders finally undergo percutaneous endoscopic gastrostomy (PEG) or nasogastric tube feeding. Their most common serious complication is aspiration pneumonia. Our objectives were to evaluate the effect of sarpogrelate (a 5-HT2A receptor blocker) on gastroesophageal reflux (GER) in these patients. METHODS: This study was performed in 5 elderly patients, aged 70-87 years with neurological disorders (stroke 4, post herpes encephalitis 1), on PEG or nasogastric feeding for 5 weeks-1 year. A 48-hour esophageal pH study was performed using the Degitrapper pH400 (Medtronic Co.). The pH monitor catheter was passed into the esophagus transnasally and positioned with the pH electrode 5cm above the lower esophageal sphincter. During the first 24 hours drug no drug was given, and during the next 24 hours we gave 100mg sarpogrelate 3 times. We analyzed the frequency of acid reflux (when the pH in the esophagus become less than 4.0 for more than 5 seconds, we defined this is 1 episode of acid reflux), frequency of acid reflux and mean pH values between drug-on and drug-off periods. An upright position was maintained for two hours after each meal. RESULTS: When the results of pH monitoring during two half days (from 7 pm to 7 am: 12 hours) was compared between drug-on term and drug-off term, mean pH value was statistically elevated from 6.0 +/- 0.2 (drug-off) to 6.5 +/- 0.4 (drug-on) (mean +/- SD, p< 0.05). Frequency and the total time of acid reflex showed no difference between the two periods. CONCLUSION: Treatment with sarpogrelate might be effective in patients with GER by blocking activated serotonin receptor in the gastrointestinal system.

Functional and bioenergetic consequences of AT1 antagonist olmesartan medoxomil in hearts with postinfarction LV remodeling.

The structural left ventricular (LV) remodeling and contractile dysfunction of hearts with postinfarction LV remodeling are benefited by angiotensin II type 1 receptor (AT1) blocker. However, the myocardial bioenergetic consequences of AT1 blocker in these hearts are not known. To investigate, we used a porcine model of postinfarction LV remodeling produced by ligation of the left circumflex coronary artery. After infarction, 7 pigs received olmesartan medoxomil (2 mg/kg) for comparison against 9 untreated and 10 normal pigs. Measurements of hemodynamics, myocardial perfusion, and myocardial bioenergetics were taken 7 weeks postinfarction. The treated group had an LV-to-body weight ratio significantly lower than the untreated group (2.69 +/- 0.70, 2.96 +/- 0.51, 3.66 +/- 0.60 g/kg for control, treated, and untreated groups, respectively). The untreated group had a mean aortic pressure significantly higher than the control (73 +/- 16, 86 +/- 14, and 94 +/- 20 mm Hg, respectively). The subendocardial phosphocreatine-to-ATP ratios of the treated group were significantly higher than that of the untreated group. The untreated group, but not the treated group, had significant reductions in mitochondrial F0F1-ATPase subunits compared with controls. Congestive heart failure as evidenced by significant ascites (100 to 2000 mL) developed in 4 of the 9 untreated animals, but was absent in the treated group. Animals with heart failure demonstrated reductions in both mitochondrial F0F1-ATPase expression and myocardial high-energy phosphate levels. Thus, severe LV dysfunction and accompanying abnormal myocardial bioenergetic phenotype were prevented by the AT1 antagonist olmesartan medoxomil.

Effects of oral beraprost sodium, a prostaglandin I2 analogue, on endothelium dependent vasodilatation in the forearm of patients with coronary artery disease.

1. Previous clinical studies with prostaglandin I(2) (PGI(2)) analogue beraprost sodium suggested the potential effects on protection of cardiovascular events in patients with peripheral artery disease. Although the mechanism is not well known, experimental studies have shown protective effects of endothelial cells. This study was designed to examine the effects of beraprost sodium on vascular endothelial function in the forearm of patients with coronary artery disease. 2. Beraprost sodium (120 microg/day) was orally administered to 14 coronary artery disease patients for 4 weeks and then stopped for 4 weeks. Eleven control patients did not receive beraprost sodium treatment. Reactive hyperemia was induced in the forearm, endothelium-dependent vasodilatation was assessed by plethysmography, and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)) was measured at baseline, 4 weeks and 8 weeks. 3. Both groups had similar reactive hyperemic responses at baseline. In the control group, reactive hyperemic response and urinary 8-iso-PGF(2alpha) remained unchanged for 8 weeks. In the beraprost group, maximum forearm blood flow increased significantly (P = 0.01) after 4 weeks of treatment and returned to baseline at 8 weeks. Duration of hyperemia increased significantly (P = 0.003) after 4 weeks, and remained greater than baseline at 8 weeks (P = 0.02). Urinary 8-iso-PGF(2alpha) decreased significantly (P = 0.03) after 4 weeks, and tended to be lower at 8 weeks (P = 0.07). Changes in reactive hyperemia correlated weakly but significantly with changes in 8-iso-PGF(2alpha) (P < 0.001). 4. Beraprost sodium decreased oxidative stress and improved forearm endothelium-dependent vasodilatation in coronary artery disease patients. The favorable effects on vascular endothelium could potentially lead to a decrease in vascular events.

Quantitative evaluation of sphingolipids using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry with sphingosylphosphorylcholine as an internal standard. Practical application to cardiac valves from a patient with Fabry disease.

Fabry disease is a glycolipid storage disorder caused by a defect of alpha-galactosidase A, and characterized by the systemic deposition of glycosphingolipids with terminal alpha-galactosyl moieties, mainly globotriaosylceramide, in tissues. Using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS), we analyzed the sphingolipids in the cardiac valves from a 49-year-old male patient with Fabry disease who suffered from congestive cardiac failure. Crude lipids were extracted from the cardiac valves with chloroform and methanol. After mild alkaline treatment of the crude lipids, a sphingolipid fraction was prepared and analyzed by DE MALDI-TOF-MS. The results were as follows: (a) ion peaks with m/z values corresponding to different ceramide trihexoside (CTH) species were detected; (b) with sphingosylphosphorylcholine (SPC) as the internal standard for semi-quantification of CTH, the relative peak height of CTH was calculated and plotted versus its amount loaded on the sample plate for MALDI-TOF-MS. The relative peak height of CTH with fatty acid C16:0 showed linearity between 0 and 50 ng CTH (regression coefficient, r>0.95); (c) semi-quantitative analysis revealed striking accumulation of CTH in the cardiac valves from the patient with Fabry disease. It was indicated that the accumulation of CTH in cardiac valves from Fabry disease patients can be detected with the DE MALDI-TOF-MS method. SPC is commercially available, and this semi-quantitative method involving MALDI-TOF-MS was found to be convenient, reliable and useful for CTH. It is expected to be applied to the quantification of CTH in small amounts of body fluids or other tissues and to clinical examination. It is also expected to be applicable to the quantification of other glycosphingolipids.

Short duration of reactive hyperemia in the forearm of subjects with multiple cardiovascular risk factors.

BACKGROUND: Peripheral vascular endothelial dysfunction is an independent predictor of cardiovascular events, and can be assessed noninvasively by measuring reactive hyperemia, either by vascular ultrasound measurement of flow-mediated vasodilatation or, less commonly, by measurement of blood flow using plethysmography. In the present study reactive hyperemia was measured using plethysmography in healthy subjects with multiple cardiovascular risk factors. METHODS AND RESULTS: Reactive hyperemia was measured following 5-min occlusion of the upper arm in 449 healthy subjects (302 men, 147 women, age range 20-70 years) with (n=352) and without (n=97) risk factors such as smoking, hypertension, diabetes mellitus, hypercholesterolemia, obesity, family history of cardiovascular disease, and menopause. Maximum blood flow and minimum vascular resistance in reactive hyperemia did not differ between subjects with and without risk factors regardless of gender. Duration of reactive hyperemia, however, was significantly shorter in subjects with risk factors. Age-adjusted mean value of duration of reactive hyperemia was significantly smaller in men with a smoking habit, diabetes mellitus, hypercholesterolemia or obesity, and in women with smoking habit, hypertension, diabetes mellitus or obesity. The number of risk factors significantly correlated with the duration of reactive hyperemia in both men (r=-0.56, p<0.001) and women (r=-0.62, p<0.001), suggesting that endothelial dysfunction increases with the number of risk conditions clustering in a single individual. CONCLUSIONS: Duration of reactive hyperemia reflects cardiovascular risk factors and decreases with the number of risk conditions. These findings suggest that the duration of reactive hyperemia measured with plethysmography is potentially useful for assessing endothelial dysfunction.

Vascular involvement in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes.

A 26-year-old man with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) was admitted to our hospital for further cardiovascular examination. A muscle biopsy demonstrated strongly succinate dehydrogenase-reactive blood vessels. Pulse wave contour analysis revealed that both capacitive and oscillatory compliance were markedly reduced in this patient compared with 45 normal age-matched control subjects. Hepatocyte growth factor was remarkably elevated in this patient over that of 10 normal control subjects. These findings suggest that a MELAS patient has not only pathologic but also functional vascular involvement. If so, patients with MELAS need systemic vascular assessment.

Reduced high serum hepatocyte growth factor levels after successful cardioversion in patients with atrial fibrillation.

1. Serum hepatocyte growth factor (HGF) is considered to be a potent marker of vascular endothelial injury. The present study was designed to examine serum HGF levels in atrial fibrillation and after successful direct current (DC) cardioversion. 2. We measured serum HGF levels before and 7 days and 1 month after DC cardioversion in 39 patients with atrial fibrillation in whom sinus rhythm was maintained for at least 7 days after DC cardioversion and in 30 age- and sex-matched normal control subjects with sinus rhythm. We also measured acetylcholine-induced changes in forearm blood flow (FBF) using venous occlusive plethysmography in 10 patients. 3. Serum HGF levels were significantly higher in the atrial fibrillation patients (both lone atrial fibrillation and with underlying heart disease) than in the controls (0.16 +/- 0.07 vs 0.10 +/- 0.04 ng/mL; P < 0.001). Seven days after successful DC cardioversion, the patients' serum HGF levels had decreased significantly (0.16 +/- 0.07 vs 0.12 +/- 0.06 ng/mL; P < 0.05) and in the 24 patients maintaining sinus rhythm 1 month after DC cardioversion, serum HGF levels decreased to control values (0.10 +/- 0.08 ng/mL at 1 month). Serum HGF levels of the 15 patients who had relapsed into atrial fibrillation 1 month after DC cardioversion tended to decrease 7 days after DC cardioversion, but increased again 1 month after DC cardioversion. Percentage changes in FBF between baseline and the highest dose of acetylcholine before and after DC cardioversion were 180 +/- 98 and 323 +/- 196%, respectively (P = 0.0051). The rate of increase in FBF at the highest dose of acetylcholine between before and after DC cardioversion correlated negatively with the rate of decrease in serum HGF levels between before and after DC cardioversion (r = -0.837; P = 0.0025). 4. This study is the first to demonstrate that serum HGF levels increase in atrial fibrillation and decrease after successful DC cardioversion. This may reflect the fact that atrial fibrillation induces vascular endothelial injury.

Increased nitric oxide in proportion to the severity of heart failure in patients with dilated cardiomyopathy: close correlation of tumor necrosis factor-alpha with systemic and local production of nitric oxide.

Recent studies have demonstrated that proinflammatory cytokines induce large amounts of nitric oxide (NO) and that the amount increases in patients with congestive heart failure (CHF). There are, however, few reports regarding the relationships between NO production, cytokines and the severity of heart failure, so the plasma concentrations of nitrite and nitrate (NOx), tumor necrosis factor-alpha (TNF-alpha) and brain natriuretic peptide (BNP) were measured in 43 patients with CHF caused by dilated cardiomyopathy and 26 age- and sex-matched normal control subjects. Forearm blood flow (FBF) was measured using plethysmography during infusions of acetylcholine and nitroglycerin and after the administration of the NO synthesis inhibitor L-NMMA (N(G)-monomethyl-L-arginine). Plasma concentrations of both NOx and TNF-alpha were significantly higher in the patient group than in the control group (p<0.001) and correlated closely with BNP concentrations (p<0.001). There was a positive relationship between NOx and TNF-alpha concentrations (r=0.80, p<0.001). Administration of L-NMMA significantly reduced FBF in both groups, and the percent change in FBF from baseline correlated significantly with TNF-alpha concentrations (r=0.63, p<0.001). The FBF response to acetylcholine was depressed in the patient group and correlated inversely with TNF-alpha concentrations. The FBF response to nitroglycerin did not correlate with TNF-alpha concentrations. The findings indicate that the concentrations of NO and TNF-alpha in patients with CHF increase in proportion to the severity of heart failure, and that TNF-alpha plays a role in the enhanced systemic and local production of NO.

Nicorandil improves myocardial high-energy phosphates in postinfarction porcine hearts.

1. Nicorandil is a potent vasodilator combining the effects of a nitrate with an ATP-sensitive potassium channel (K(ATP)) opener. Because the postinfarct remodelled heart has increased vulnerability to subendocardial hypoperfusion, it is possible that the vasodilator effects of nicorandil could cause transmural redistribution of blood flow away from the subendocardium. Alternatively, the K(ATP) channel opening effects of nicorandil could exert a beneficial effect on mitochondrial respiration. Consequently, the present study was performed to examine the effect of nicorandil on energy metabolism in the postinfarct heart. 2. Studies were performed in swine in which myocardial infarction produced by proximal left circumflex coronary artery ligation had resulted in left ventricular remodeling. [(31)P] nuclear magnetic resonance spectroscopy (MRS) was used to examine the myocardial energy supply/demand relationship across the left ventricular wall while the transmural distribution of blood flow was examined with radioactive microspheres. Data were obtained during baseline conditions and during infusion of nicorandil (100 microg, i.v., followed an infusion of 25 microg/kg per min). 3. Nicorandil caused coronary vasodilation with a preferential increase in subepicardial flow; however, subendocardial flow also increased significantly. Nicorandil had no significant effect on the rate-pressure product or myocardial oxygen consumption. The ratio of phosphocreatine (PCr)/ATP determined with MRS was abnormally depressed in remodelled hearts (2.01 +/- 0.11, 1.85 +/- 0.10 and 1.59 +/- 0.11 for subepicardium, midwall and subendocardium, respectively) compared with normal (2.22 +/- 0.11, 2.01 +/- 0.15 and 1.80 +/- 0.09, respectively). Nicorandil had no effect on the high-energy phosphate content of normal hearts. However, nicorandil increased the PCr/ATP ratio in the subendocardium of remodelled hearts from 1.59 +/- 0.11 to 1.87 +/- 0.10 (P < 0.05). 4. Although nicorandil caused modest redistribution of blood flow away from the subendocardium of the postinfarct left ventricle, this was associated with an increase of the PCr/ATP ratio towards normal. These results suggest that nicorandil exerts a beneficial effect on energy metabolism in the subendocardium of the postinfarct remodelled left ventricle.

Impaired exercise-induced vasodilatation in chronic atrial fibrillation--role of endothelium-derived nitric oxide.

Exercise capacity is often reduced in patients with atrial fibrillation (AF), but very few studies have focused on changes in endothelial function as a potential mechanism for the exercise limitation. The present study used using venous occlusion plethysmography to investigate whether nitric oxide (NO)-mediated vasodilatation is attenuated during exercise in patients with AF by measuring forearm blood flow (FBF) in 10 patients at rest and immediately after 2 levels of rhythmic handgrip exercise, before and after inhibition of NO synthesis with N(G)-monomethyl-L-arginine (L-NMMA, 100 micromol). The measurements were repeated 1 day after restoration of sinus rhythm by cardioversion. FBF responses to graded doses of acetylcholine (ACh) were also observed before and after cardioversion. Heart rate decreased after cardioversion, but blood pressure did not change. FBF at rest was not affected by cardioversion, but at the highest level of exercise it increased from 28.4+/-2.3 ml x min(-1) x dl(-1) before to 39.4+/-3.2 ml x min(-1) x dl(-1) after cardioversion (p<0.05). L-NMMA significantly decreased FBF at rest (p<0.01) and depressed the increase in FBF response to exercise after (p<0.01), but not before cardioversion. The FBF response to ACh was also accelerated significantly after cardioversion. The present results provide new evidence that NO bioavailability is depressed at rest and during exercise in patients with AF.

High plasma brain natriuretic polypeptide level as a marker of risk for thromboembolism in patients with nonvalvular atrial fibrillation.

BACKGROUND AND PURPOSE: Assessment of left atrial appendage (LAA) function with transesophageal echocardiography is useful for detecting patients at high risk for thromboembolism as a result of atrial fibrillation (AF). A recent study reported that the atrium is the main source of brain natriuretic polypeptide (BNP) in AF patients without overt heart failure. The purpose of this study was to assess a possible relationship between LAA function and plasma BNP levels in nonvalvular AF. METHODS: Thirty-four consecutive patients with chronic nonvalvular AF (age, 69+/-9 years) underwent transesophageal echocardiography and plasma BNP measurement. Thirteen patients with a history of thromboembolism or echocardiographic evidence of thrombus (E + group) were compared with 21 AF patients without complications (E- group). RESULTS: The E+ group patients demonstrated greater impairment of LAA velocity and higher plasma BNP levels than the E- group patients (LAA velocity: 12+/-6 versus 31+/-17 cm/s, P<0.05; plasma BNP: 126+/-53 versus 86+/-45 ng/L, P<0.05). Overall analysis of the continuous variables with multiple logistic regression analysis revealed that BNP was a significant predictor of thromboembolism. There was a weak but significant negative correlation between plasma BNP levels and LAA flow velocity (r=0.38, P<0.05). No intergroup difference in plasma atrial natriuretic polypeptide levels was found. CONCLUSIONS: The present data suggest the usefulness of measuring plasma BNP levels, which may reflect augmented atrial secretion of BNP from the impaired atrial myocardium, in detecting patients at high risk for thromboembolic complications in nonvalvular AF.