Electrophysiological Characteristics of Localized Reentrant Atrial Tachycardia Occurring After Catheter Ablation of Long-Lasting Persistent Atrial Fibrillation

Background: Mapping of recurrent atrial tachycardia (AT) after extensive ablation for long-lasting persistent atrial fibrillation (AF) is complex. We sought to describe the electrophysiological characteristics of localized reentry occurring after ablation of long-lasting persistent AF.
Methods: Out of 70 patients undergoing catheter ablation of long-lasting persistent AF, 9 patients (13%, 55 ± 8 years, 8 males) in whom localized reentry was demonstrated in a repeat ablation were studied. Localized reentry was defined as reentry in which the circuit was localized to a small area and did not have a central obstacle. The mechanism of AT was determined by electroanatomical and entrainment mapping.
Results: Nine localized reentries with cycle length of 243 ± 41 ms were mapped in 9 patients. The location of AT was the left atrial appendage in 4 patients, anterior left atrium in 2, left septum in 2, and mitral isthmus in 1. In all ATs, a critical isthmus of <10 mm in width was identified in the vicinity of the prior linear lesions or ostia of isolated pulmonary veins. Ablation of the critical isthmus, which was characterized by continuous low-voltage activity (median voltage: 0.15 mV, mean duration: 117 ± 31 ms), terminated AT and rendered it noninducible. Additionally, ablation was performed for all of inducible ATs. At 11 ± 7 months after the procedure, 8 of 9 patients (89%) were free from any arrhythmias.
Conclusions: After ablation of long-lasting persistent AF, localized reentry may arise from a site in the vicinity of the prior ablation lesions. Ablation of the critical isthmus eliminates the arrhythmia.     

Predominant Production of Amniotic Interleukin-1α in Cases With Premature Rupture of the Membranes

PROBLEM: The physiological significances of the two known subtypes of interleukin-1 (IL-1) in amniotic fluid (AF) were examined by measurements of their concentrations and detection of their location. METHOD: Each IL-1 subtype in AF collected from 61 patients were examined by newly developed enzyme-linked immunosorbent assay with high sensitivity. Placenta and umbilical cord from 17 patients were examined immunohistochemically for localization of IL-1. RESULTS: Different types of IL-1 were predominant in AF; the mean (± SE) concentration of IL-1β (412.8 ± 105.4pg/ml) was significantly higher (P<0.01) than that of IL-1α(116.4± 26.7 pg/ml) in cases with spontaneous vaginal delivery, whereas the concentration of IL-1α (243.1 ±81.4pg/ml) was significantly higher(P<0.01)than that of IL-1β (139.7±59.4pg/ml) in cases with premature rupture of the membranes (PROM) without intrauterine infection. In these cases, immunohistochemical studies revealed the presence of IL-1α in the trophoblastic layer of the placenta and epithelium of the umbilical cord. CONCLUSIONS: Amniotic IL-1α was detected predominantly in cases with PROM, and it is thought to be produced in placenta and fetal skin keratinocyte.     

Atrial Ectopy Originating from the Posteroinferior Atrium During Radiofrequency Catheter Ablation of Atrioventricular Nodal Reentrant Tachycardia

Atrial ectopy sometimes appears during RF ablation of the slow pathway in patients with atrioventricular nodal reentrant tachycardia (AVNRT). However, its origin, characteristics, and significance are still unclear. To examine these issues, we analyzed 67 consecutive patients with AVNRT (60 with slow-fast AVNRT and 7 with fast-slow AVNRT), which was successfully eliminated by RF ablation to the sites with a slow potential in 63 patients and with the earliest activations of retrograde slow pathway conduction in 4 patients. During successful RF ablation, junctional ectopy with the activation sequence showing H-A-V at the His-bundle region appeared in 52 patients (group A) and atrial ectopy with negative P waves in the inferior leads preceding the QRS and the activation sequence showing A-H-V at the His-bundle region appeared in 15 patients (group B). Atrial ectopy was associated with (10 patients) or without junctional ectopy (5 patients). Before RF ablation, retrograde slow pathway conduction induced during ventricular burst and/or extrastimulus pacing was more frequently demonstrated in group B than in group A (9/15 [60%] vs 1/52 [2%], P < 0.001). Successful ablation site in group A was distributed between the His-bundle region and coronary sinus ostium, while that in group B was confined mostly to the site anterior to the coronary sinus ostium. In group B, atrial ectopy also appeared in 21% of the unsuccessful RF ablations. In conclusion, atrial ectopy is relatively common during slow pathway ablation and observed in 8% of RF applications overall and 22% of RF applications that successfully eliminated inducible AVNRT. Atrial ectopy appears to be closely related to successful slow pathway ablation among patients with manifest retrograde slow pathway function.     

Specific type IV phosphodiesterase inhibitor ameliorates thioacetamide-induced liver injury in rats

Background and Aims:  Rolipram is a specific type IV phosphodiesterase inhibitor that suppresses the activity of immune cells and the production of pro-inflammatory cytokines. In this study, we assessed the effect of rolipram on acute liver injury using thioacetamide (TAA)-induced liver injury in rats as a model.
Methods:  Rats were treated with rolipram (0.5–5 mg/kg, intraperitoneally) or vehicle and injected 30 min later with TAA (100 mg/kg, subcutaneously). Serum transaminase concentrations and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and growth related oncogene/cytokine-induced neutrophil chemoattractant-1 (GRO/CINC-1) levels were measured and livers were examined for microscopic changes. Dose-dependent protection against TAA liver injury was based on transaminase levels and inflammatory cytokine production, and was measured 9 h after TAA when the peak release of cytokines occurred.
Result:  Rolipram suppressed liver injury based on serum aspartate transaminase (AST), alanine transaminase (ALT) and histology and reduced TNF-α, IL-1β and GRO/CINC-1 levels. Rolipram, at doses of 0.5–5 mg/kg, suppressed serum transaminase and TNF-α production in a dose-dependent manner, and these effects were significant at doses of 2.5 and 5 mg/kg.
Conclusion:  In our rodent model of acute liver injury, rolipram clearly reduced liver damage and inhibited pro-inflammatory cytokine production. These results suggest that specific type IV phosphodiesterase inhibitors, such as rolipram, have potent hepatoprotective effects that are associated with suppressing inflammatory cytokine production.     

A Mutant Exhibiting Abnormal Habituation Behavior in Caenorhabditis elegans

The acquisition and retention of information by the nervous system are major processes of learning. Habituation is a simple learning process that occurs during repeated exposure to harmless stimuli. C. elegans is habituated when repeatedly given mechanical stimuli and recover from the habituation when the stimuli are stopped. A habituation abnormal mutant was isolated and assigned to a new gene hab-1 whose mutation causes slow habituation. The hab-1 mutant phenotype is remarkable at short time interval stimuli. However, hab-1 mutant worms show normal dishabituation. Ablations of neurons constituting the neural circuit for mechanical reflexes did not abolish abnormalities caused by the hab-1 mutation.     

TARGETED EXPRESSION OF TEMPERATURE-SENSITIVE DYNAMIN TO STUDY NEURAL MECHANISMS OF COMPLEX BEHAVIOR IN Drosophila

Sites in the brain that show functional, sexual dimorphism in courtship behavior have been mapped at high resolution in male/female mosaics of Drosophila melanogaster. The sex mosaics were produced by enhancer-trap expression of GALA driving the female-spliced form of the transformer gene (tra), revealing sites in the dorsal brain, lateral proto-cerebrum, suboesophageal, thoracic and abdominal ganglia, and suggesting the importance of cross-talk between these regions in the implementation of the courtship sequence.     

Effect of drinking on the outcome of cirrhosis in patients with hepatitis B or C

Survival rates were calculated for 251 patients with cirrhosis of the liver but without hepatocellular carcinoma, primary biliary cirrhosis, or autoimmune cirrhosis who underwent laparoscopy during the past 21 years at the authors' hospital. The survival rates were calculated by the Kaplan-Meier method. Stored serum was assayed for hepatitis B surface antigen (HBsAg) and antibodies to the hepatitis C virus (HCV). Patients with alcoholic cirrhosis had significantly better survival rates than patients with HBsAg, HCV, or both. Differences in survival rates between patients with hepatitis B and C were insignificant. In both groups, habitual drinkers had a significantly lower survival rate. The results suggested that alcohol accelerates liver damage in subjects with viral hepatitis.     

The protective effect of pyrroloquinoline quinone and its derivatives against carbon tetrachloride-induced liver injury of rats

Pyrroloquinoline quinone (PQQ) and its derivative, oxazo pyrroloquinoline (OPQ-G), protected rats from experimental liver injury induced by carbon tetrachloride (CCl₄) in vivo. This effect was observed after an intraperitoneal injection of 5 mg/kg PQQ or OPQ-G, which was given twice, 10 min and 1 h before CCl₄ administration. Pyrroloquinoline quinone protected primary cultured rat hepatocytes from CCl₄ toxicity in vitro. This protection was most effective at a concentration of 3 μmol/L PQQ. Pyrroloquinoline quinone derivatives (oxazo pyrroloquinoline, methyl-thioethyl oxazo pyrroloquinoline and PQQ-allylester) also protected the hepatocytes from CCl₄ toxicity. Pyrroloquinoline quinone and its derivatives inhibited the lucigenin-enhanced chemiluminescence from isolated hepatocytes initiated by CCl₄. These results suggest that eliminating free radicals is one of the protective mechanisms of PQQ and its derivatives against CCl₄-induced liver injury.     

Detection of the preneoplastic lesions of small hepatocellular carcinoma in cirrhotic livers

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferative conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published criteria for sHCC and by the proliferative activity of the lesions as examined with monoclonal antibodies against DNA polymerase alpha and proliferating cell nuclear antigen. The four patients with FCA composed of basophilic hepatocytes were classified by the criteria as having sHCC; cells had features similar to those of sHCC. Two of these four patients with FCA were found to have HCC several years later. The number of hepatocytes stained for proliferating cell nuclear antigen was 72 and 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microscopy. In this patient, the number of hepatocytes stained for DNA polymerase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be preneoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic hepatocytes seem to be small cells with basophilic cytoplasm, with a large nucleus to cytoplasm ratio, finely indented nuclei with a smaller amount of condensed chromatin than normal, and poorly to moderately developed organelles.