Effect of Corticosteroid Therapy on Ventricular Arrhythmias in Patients with Cardiac Sarcoidosis

Background: Ventricular arrhythmias are one of the main causes of sudden death in cardiac sarcoidosis (CS). Little is known about the efficacy of corticosteroid therapy for ventricular arrhythmias in CS. Methods: Thirty‐one CS patients presenting premature ventricular contractions (PVCs, ≥300/day) were investigated. Fourteen patients had nonsustained ventricular tachycardia (NSVT). All of patients were treated with corticosteroid, and the initial dosage is 30 mg/day of prednisone, which was tapered over a period of 6 months to a maintenance dosage of 10 mg/day. Twenty‐four hour Holter monitoring, signal averaged electrocardiography (SAECG), echocardiography, gallium‐67 scintigraphy, serum angiotensin converting enzyme (ACE) and plasma B‐type natriuretic peptide (BNP) concentrations were assessed before and after corticosteroid therapy. Results: As a whole, there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. However, the less advanced LV dysfunction patients (EF ≥ 35%, n = 17) showed significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425, P = 0.048) and in the prevalence of NSVT (from 41 to 6%, p = 0.039). Late potentials on SAECG were abolished in 3 patients. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium‐67 uptake compared with the advanced LV dysfunction group (EF < 35 %, n = 14). In the advanced LV dysfunction patients, there were no significant differences in these parameters. Conclusions: Corticosteroid therapy may be effective for ventricular arrhythmias in the early stage, but less effective in the late stage. Ann Noninvasive Electrocardiol 2011;16(2):140–147     

Elevated levels of both cardiomyocyte membrane and myofibril damage markers predict adverse outcomes in patients with chronic heart failure.

BACKGROUND: Recent studies have shown the presence of ongoing myocardial damage in patients with chronic heart failure (CHF) detected by myofibril and membrane damage markers, cardiac troponin T (TnT) and heart-type fatty acid-binding protein (H-FABP), which identifies patients at increased risk of a future cardiac event (CE: death or rehospitalization because of worsening CHF). There is a difference between TnT and H-FABP in their release kinetics following myocardial damage. METHODS AND RESULTS: TnT and H-FABP were measured in 103 patients with CHF and in 31 controls. Patients were classified into 4 groups based on detectable (>or=0.01 ng/ml) or undetectable TnT (TnT+ or TnT-) and H-FABP >or= or <4.5 ng/ml (mean + 2 standard deviations in controls) (high-H-FABP or low-H-FABP). Kaplan-Meier analysis showed that the CE-free rate (n=43) was significantly lower in patients with TnT+ and high-H-FABP than in patients in the other 3 groups (patients with TnT+ and low-H-FABP, TnT- and high-H-FABP, and TnT- and low-H-FABP; p=0.02, p=0.001 and p=0.0002, respectively). In stepwise multivariate Cox proportional hazard analysis, TnT+ (p=0.01) and high-H-FABP (p=0.04) were independent predictors of future CE. CONCLUSIONS: Elevated levels of both TnT and H-FABP predict adverse outcomes in CHF patients.     

Systematic review of the epidemiology of gastroesophageal reflux disease in Japan

Background  

Epidemiological studies of gastroesophageal reflux disease (GERD) in Japan vary in design. This systematic review examines the prevalence of GERD in Japan, distinguishing between study methodologies, and reports on changes over time and factors potentially associated with GERD.     

Comparison of an increased dosage regimen of rabeprazole versus a concomitant dosage regimen of famotidine with rabeprazole for nocturnal gastric acid inhibition in relation to cytochrome P450 2C19 genotypes

BACKGROUND AND OBJECTIVE: A concomitant dosage regimen of a histamine 2 receptor antagonist with a proton pump inhibitor (PPI) effectively decreases the incidence of nocturnal acid breakthrough, which is one of the problems encountered when acid-related diseases are treated with a PPI alone. We compared the effectiveness of an increased dosage regimen of rabeprazole with that of a concomitant dosage regimen of rabeprazole with famotidine, relative to cytochrome P450 (CYP) 2C19 genotype status, on nocturnal acid inhibition. METHODS: Fifteen Helicobacter pylori-negative volunteers, consisting of 5 homozygous extensive metabolizers (EMs), 6 heterozygous EMs, and 4 poor metabolizers (PMs) of CYP2C19, took 20 mg rabeprazole, 40 mg rabeprazole, and 20 mg rabeprazole plus 20 mg famotidine at bedtime (at 10 PM) for 8 days. The subjects then underwent 24-hour intragastric pH monitoring on day 8. RESULTS: For the 20-mg rabeprazole, 40-mg rabeprazole, and concomitant dosage regimens, the median percent times and ranges when nocturnal intragastric pH values were lower than 4.0 were 78.8% (47.5%-98.0%), 45.3% (29.0%-52.2%), and 15.5% (0.0%-40.8%), respectively, for homozygous EMs; 51.0% (7.0%-91.6%), 41.3% (33.0%-59.0%), and 18.5% (8.4%-31.9%), respectively, for heterozygous EMs; and 4.5% (2.0%-31.2%), 9.5% (0.0%-31.1%), and 9.3% (0.0%-14.7%), respectively, for PMs. Although significant differences in acid inhibition between the different CYP2C19 genotypes were observed when rabeprazole alone was given (P = .016 for 20 mg rabeprazole and P = .023 for 40 mg rabeprazole), such differences were not observed when famotidine was concomitantly given (P = .206). CONCLUSIONS: The combination regimen of famotidine plus rabeprazole is more effective for nocturnal acid inhibition in homozygous and heterozygous EMs than the increased dosage regimen of rabeprazole. This concomitant therapy could be a rescue regimen for patients with nocturnal acid breakthrough refractory to a standard PPI therapy who are likely to be CYP2C19 EMs.     

Identification of a cardiac isoform of the murine calcium channel alpha1C (Cav1.2-a) subunit and its preferential binding with the beta2 subunit

We describe a cardiac muscle isoform of the voltage-dependent calcium channel alpha1 subunit, which corresponds to the rabbit ortholog of alpha1C-a (Cav1.2a). We also cloned smooth muscle isoforms alpha1C-b (Cav1.2b) and alpha1C-d (Cav1.2d). Differences among these three isoforms lie within the N-terminal region (exon 1A or 1B), the sixth transmembrane segment of domain I (exon 8A or 8B), and the use of exon 10, which forms the intracellular loop between transmembrane domains I and II. Two-hybrid analysis revealed interactions among the three alpha1 isoforms and beta subunits. In vitro overlay and immunoprecipitation analyses revealed preferential binding between alpha1C-a and beta2, which is also expressed at a high level in the heart.     

Tolerance to H2 receptor antagonist correlates well with the decline in efficacy against gastroesophageal reflux in patients with gastroesophageal reflux disease

BACKGROUND AND AIM: The attenuated antisecretory activity of H2 receptor antagonists (H2RA) during continuous administration is known as the tolerance phenomenon. The authors recently clarified that presence or absence of Helicobacter pylori infection influences the occurrence of the tolerance phenomenon. The aim of this study was to clarify whether tolerance to H2RA is correlated with attenuation of the inhibitory effect against gastroesophageal acid reflux in patients with gastroesophageal reflux disease (GERD). METHODS: Ten male patients with GERD symptoms and abnormal gastroesophageal reflux were investigated by pH monitoring on days 1 and 15 of continuous oral famotidine administration at 20 mg twice daily, and H. pylori infection was examined using the urea breath test. RESULTS: Intragastric and intraesophageal acidity were significantly decreased on the first day of famotidine administration, but then increased during the 15-day administration period in seven patients who were negative for H. pylori. In contrast, the efficacy of famotidine against gastric acid secretion and gastroesophageal acid reflux was not attenuated in three H. pylori-positive patients. The changes in GERD symptoms were correlated with the change in the degree of gastroesophageal reflux. CONCLUSION: The presence or absence of tolerance to H2RA during 15-day administration is correlated with the efficacy for inhibition of gastroesophageal acid reflux.     

Angioscopic study of silent plaque disruption in nonischemic related coronary artery in patients with stable ischemic heart disease

Plaque disruption, which may be associated with some coronary risk factors, plays a key role in the development of acute coronary syndromes and progression of atherosclerosis. However, the clinical profile of asymptomatic plaque disruption in stable ischemic heart disease has not been well evaluated. The aim of the present study was to investigate the frequency and determinants of silent plaque disruption (SPD) in patients with stable ischemic heart disease using coronary angioscopy. Forty-one patients with stable angina or old myocardial infarction (OMI) without any complaints within 3 months were included in the present study. Angioscopy was successfully performed through 49 nonischemic related coronary arteries. The presence of SPD and coronary risk factors were recorded. Silent plaque disruption was found in 12 patients with stable ischemic heart disease (12/41, 29.3%), and the frequency of SPD in nonischemic related coronary arteries was 26.5% (13/49). A significantly higher frequency of SPD was noted in yellow plaques than in white plaques (35.3% versus 6.7%, P = 0.043). Overall, the independent clinical risk factors of SPD in nonischemic related coronary arteries were diabetes mellitus (P = 0.018; OR, 18.8209; 95% CI, 1.6525 to 214.3523) and hypertension (P = 0.0313; OR, 6.6485; 95% CI, 1.1850 to 37.3019). These results suggest silent plaque disruption was commonly observed in nonischemic related coronary arteries in patients with stable ischemic heart disease and its determinants were diabetes mellitus and hypertension.     

Effect of chronic methylene blue administration on hypoxemia in rats with common bile duct ligation

Aim: Acute administration of methylene blue (MB) can reverse hypoxemia in patients with hepatopulmonary syndrome (HPS). We evaluated the effect of chronic MB administration in common bile duct‐ligated rats, which develop HPS by 5 weeks after surgery. Methods: A total of 96 Sprague–Dawley rats were used, including 63 rats with common bile duct ligation (CBDL), 22 sham‐operated rats and 11 normal control rats. MB (6 mg/kg) was injected s.c. once a day for 4 weeks. Evaluation of hemodynamics and intrapulmonary vascular dilatation (IPVD), as well as blood sampling for arterial blood gas analysis, were done under conscious and unrestrained conditions. Hemodynamics were assessed by the reference sample method using ¹⁴¹Ce‐microspheres (15 µm in diameter), and IPVD was also determined by i.v. injection of these microspheres. Histological examination of the lungs was done with hematoxylin–eosin staining and immunohistochemical staining for von Willebrand factor or vascular endothelial growth factor. Results: Both the arterial oxygen tension and alveolar–arterial oxygen difference were significantly improved in MB‐treated CBDL rats. The hyperdynamic circulation and splanchnic hyperemia seen in untreated CBDL rats were also alleviated by MB treatment. However, IPVD was not affected by MB. Histological examination of the lungs indicated that MB treatment reduced the proliferation of alveolar capillary vessels and angiogenesis, leading to improvement of arterial dysoxygenation. Hepatic synthetic and detoxification functions, as well as renal function, were not altered by MB treatment. Conclusion: Methylene blue may be a candidate treatment for HPS that does not cause deterioration of hepatic or renal function.     

T-type Ca2+ channels and cardiac pacemaker activity

It is well known that T-type Ca(2+) channels differ from L-type Ca(2+) channels on the basis of their low-voltage activation range and rapid inactivation, and therefore can contribute to the pacemaker activity of sinoatrial node cells in the heart. However, proper elucidation of their function on the pacemaker activity has been hampered by the lack of selective pharmacology as well as cell-to-cell difference in the amplitude of T-type Ca(2+) current. In the present study, therefore, we investigated the effects of mibefradil, a selective T-type Ca(2+) channel blocker, on the spontaneous action potential of rabbit sinoatrial node cells. Mibefradil strongly inhibited the spontaneous action potential. In particular, suppression of the slow diastolic depolarization was more marked than that had been expected from a sole inhibition of T-type Ca(2+) channels. T-type Ca(2+) channels may be an important contributor to automaticity in heart cells. Alternatively, mibefradil might have blocked other current system (s) which serves as the main pacemaker current, and thereby inhibited the pacemaker activity.     

Comparison of Postoperative Motility in Hand-Sewn End-to-End Anastomosis and Functional End-to-End Anastomosis: An Experimental Study in Conscious Dogs

Background and Aims  

The objective of this study is to compare the postoperative motility between hand-sewn end-to-end anastomosis and functional end-to-end anastomosis.