The Role of Catheter Ablation Techniques in the Treatment of Classic (Type 1) Atrial Flutter

Several attempts at circuit interruption of type 1 atrial flutter by means of surgical or catheter techniques have been published. We recently reported the results of a series of patients who underwent catheter fulguration of the low septal right atrium, with a mean follow-up of almost 3 years. True electrophysiological success was observed in 7/14 patients (50%). Clinical success, defined as absence of symptoms, was observed in 8/14 (57%) in this patient population. No serious complications were encountered, but the potential risks of DC shock, and the experience that we gained in right atrial mapping using this approach, led us to reconsider the role of atrial DC ablation in these patients. Additional studies assessing the meaning of fragmented electrograms, and identification of one for of severall slow conduction areas of the reentrant circuit are ongoing.     

Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.

Interleukin 1 (IL-1) may be a key mediator of inflammation and tissue damage in inflammatory bowel disease (IBD). In rabbits with immune complex-induced colitis, IL-1 alpha and beta mRNA levels were detectable at 4 h, peaked at 12 but were absent at 96 h after the induction of colitis. Colonic IL-1 tissue levels were measured by specific radioimmunoassays. IL-1 alpha was significantly elevated at 4 h (9.4 +/- 1.5 ng/g colon), progressively increased at 48 h (31 +/- 5.8 ng/g) and then decreased by 96 h (11.5 +/- 3.4 ng/g). IL-1 beta levels were 2.0 +/- 0.5 ng/g colon at 4 h, 5.0 +/- 1.6 ng/g at 48 h and undetectable by 96 h. By comparison, colonic levels of PGE2 and LTB4 were unchanged during the first 12 h and did not become elevated until 24 h. IL-1 alpha levels were highly correlated with inflammation (r = 0.885, P less than 0.0001), edema (r = 0.789, P less than 0.0001) and necrosis (r = 0.752, P less than 0.0005). Treatment with a specific IL-1 receptor antagonist (IL-1 ra) before and during the first 33 h after the administration of immune complexes markedly reduced inflammatory cell infiltration index (from 3.2 +/- 0.4 to 1.4 +/- 0.3, P less than 0.02), edema (from 2.2 +/- 0.4 to 0.6 +/- 0.3, P less than 0.01) and necrosis (from 43 +/- 10% to 6.6 +/- 3.2%, P less than 0.03) compared to vehicle-matched colitis animals. These studies demonstrate that (a) IL-1 gene expression and synthesis occur early in the course of immune complex-induced colitis; (b) are significantly elevated for 12 h before the appearance of PGE2 and LTB4; (c) tissue levels of IL-1 correlate with the degree of tissue inflammation and; (d) specific blockade of IL-1 receptors reduces the inflammatory responses associated with experimental colitis.     

Transforming growth factor-alpha (TGF-alpha) is not needed for malignant transformation in experimental colitis

BACKGROUND: Transforming growth factor-alpha (TGF-alpha) is a key mediator of colonic mucosal protection and/or repair mechanisms in orally induced acute dextran sodium sulphate (DSS) colitis. However, it also has been suggested that TGF-alpha may contribute to malignant transformation in the colon. The aim of the studies was to determine whether TGF-alpha is needed for malignant transformation in orally induced chronic DSS colitis using TGF-alpha deficient mice (wa-1) and Balb/c mice, a strain competent in TGF-alpha. METHODS: Chronic colitis was induced by oral administration of DSS (5%) for 7 days followed by drinking water for 10 days in wa-1 and Balb/c mice (n = 20, per group). In the two subsequent cycles (7 days DSS, 10 days water) 3% DSS-water was utilized due to a high mortality in the wa-1 group. Mucosal injury severity was assessed histologically and graded (three grades). A crypt damage score (CDS) reflecting all three grades of mucosal pathology was calculated. Mucosal dysplasia and cancerous lesions were noted. RESULTS: Seven per cent of the entire colonic mucosa was completely destroyed in wa-1 animals compared to 3% in Balb/c mice (P < 0.05). The CDS was 10.2 +/- 0.4 and 4.8 +/- 0.3 in wa-1 and Balb/c mice, respectively (P < 0.05). Fifteen incidences of mucosal dysplasia were found in the 10 surviving wa-1 animals and 31 incidences were found in 20 Balb/c animals. In both groups, one fully developed adenomatous cancerous lesion was present. CONCLUSIONS: The markedly increased severity of mucosal injury in chronic induced DSS colitis in TGF-alpha deficient wa-1 mice compared to Balb/c mice further substantiates that endogenous TGF-alpha is a pivotal mediator of protection and/or healing mechanisms in the colon. The appearance of dysplastic and cancerous lesions in TGF-alpha deficient animals suggests that TGF-alpha per se is not essential for malignant mucosal cell transformation in colitis.     

Toxic oxygen metabolites induce vasoconstriction and bronchoconstriction in isolated, plasma-perfused rat lungs

Effects of toxic oxygen metabolites (TOM) on the pulmonary vascular bed and airways were studied in isolated, plasma-perfused rat lungs. TOM were generated by xanthine oxidase (XO) (0.1 or 0.25 unit.ml-1) and hypoxanthine (HX) (1 mol.l-1). In vitro measurements by chemiluminescence indicated that the major oxygen metabolite generated by XO and HX was H2O2. Measurements of PO2 in the perfusate as an indicator of O2-consumption suggested that production of TOM by XO and HX was finished within 30 min. XO and HX induced an early dose-dependent bronchoconstriction and a late increase in transpulmonary pressure (Ptp). Pulmonary arterial pressure (Ppa) increased gradually and levelled off within 30 min with low-dose XO, but not with high-dose XO. As judged by weight increase of the lungs, interstitial edema occurred regularly. Allopurinol, an inhibitor of XO, blocked the lung responses caused by XO and HX. Catalase attenuated all lung responses induced by XO and HX, while superoxide dismutase had no effect. The hydroxyl radical scavenger dimethylsulfoxide abolished the increase in Ptp and attenuated the increase in Ppa, but did not consistently protect the lungs from edema development. This study shows that TOM induce vasoconstriction, bronchoconstriction and lung edema in plasma-perfused rat lungs, mainly due to generation of H2O2 and the hydroxyl radical.     

Atrial Septal Versus Atrial Appendage Pacing:

HERMIDA, J.-S., et al. : Atrial Septal Versus Atrial Appendage Pacing: Feasibility and Effects on Atrial Conduction, Interatrial Synchronization, and Atrioventricular Sequence. Atrial septal (Se-P) and atrial appendage pacing (Ap-P) were compared in a randomized, controlled study to assess the feasibility, the reliability, and the effects of Se-P on atrial conduction, interatrial synchronization, and the AV sequence. The main baseline characteristics of the patients were comparable in both groups. There was no difference in feasibility or reliability between the two techniques. Compared to Ap-P   (n = 28)   , Se-P   (n = 28)   decreased the P wave duration, left atrial electromechanical delay (LAEMD), and interatrial interval (−1.6% vs   +28%, P < 0.001; −3%   vs   + 30%, P < 0.001; −130%   vs   + 78%, P < 0.001   ); it induced a smaller increase of the right AEMD, a slight reversal of the timing of the atrial systoles and a shortening of the PR interval (−13% vs   + 25%, P < 0.001   ) and of the interval separating atrial systoles from ventricular activation. Finally, the shortening of the PR interval was smaller during high Se-P versus low Se-P. Se-P avoids the undesirable prolongation of the atrial, interatrial, and AV conductions observed during Ap-P. In addition, Se-P creates a slight reversal of the timing of the atrial systoles and induces a shortening of PR interval, the extent of which could depend on the height of the pacing site on the septum. (PACE 2003; 26[Pt. I]:26–35)     

MALIGNANT HYPERTHERMIA IN BELGIAN LANDRACE PIGS RESTED OR EXCERCISED BEFORE EXPOSURE TO HALOTHANE

Thirteen of 31 Belgian Landrace pigs developed malignant hyperthermia(MH) after breathing halothane. A short period of exercise 1h before the administration of the triggering agent increasedthe incidence of the syndrome to 100% in eight similar pigs.Clinical symptoms were more marked and developed more rapidlyin the exercised pigs. All the reacting pigs became typicallyacidotic, developed rigor and died. Serum Na⁺, K+, Ca2⁺, c.p.k.,l.d.h. and protein concentrations were increased to a variableextent during the reaction and there was an increase in p.c.v.also. No hyper-glycaemia was detected in pigs which were restedbefore receiving halothane. Four of the eight exercised pigsbecame markedly hyperglycaemic and plasma noradrenaline increasedto higher values. Phosphocreatine and ATP decreased to low valuesand lactate increased in the muscles of all pigs which reacted.At the time of death, muscle glycogen had decreased significantlyin the rested, but not in the exercised, MH pigs. ^*Present address: ARC Meat Research Institute, Langford, BristolBS18 7DY.     

Metabolism of xylitol in dental plaque

Abstract – It has been reported previously that xylitol added to glucose used to challenge dental plaque in vivo caused a reduced acid formation. The aim of the present study was to approach the mechanism by which xylitol may affect glucose catabolism in plaque bacteria. Suspensions of freshly collected 4-day-old plaque bacteria were ineubated, one batch with labeled xylitol, one with labeled glucose, in vitro at 37°C. Samples of cells were taken out at time intervals, collected on paper discs and subjected to scintillation counting. It was observed that the plaque bacteria took up xylitol, the uptake increasing with incubation of more than 3–4 h, whereas the same cells took up glucose immediately. Cells which had taken up xylitol were extracted with boiling water, extracts concentrated and applied on thin-layer chromatography sheets. A radioactive component with mobility like xylitol-5-phosphate was isolated from the cell extracts, and also a component where labeled xylitol was associated with macromolecules. It is suggested that the accumulation of the metabolities within the cells inhibits glycolysis.     

Action of beer and its ingredients on gastric acid secretion and release of gastrin in humans

The intragastric action of beer and its known ingredients before and after fermentation on gastric acid secretion and release of gastrin was studied in healthy humans. None of 11 tested ingredients of fermented beer (2 x 500 mL, pH 5.5, given either alone or in combination) or hop extract had any significant effect. Finished beer (6 weeks old) and new beer were potent stimuli of acid output, causing 93% and 76% of the incremental maximal acid output in response to pentagastrin (6 micrograms/kg SC), respectively. Before the addition of yeast, preproducts of beer were considerably less potent. Thus, first and finished wort caused only a minor acid response which was 48% and 46% of maximal acid output. Foreign fermentation in first and finished wort is presumably the reason for the stimulatory action because glucose solutions in concentrations (11.5% wt/vol) seen in wort did not stimulate acid secretion. However, glucose solutions to which yeast was added, resulting in fermentation, were as potent stimuli of acid secretion as beer. Lyophilization of beer at pH 11.0 and dialysis (cutoff mol wt, 1000) removed the stimulatory substances. The plasma gastrin responses paralleled the gastric acid response to the different stimulants. It was concluded that (a) the addition of yeast to finished wort and the following alcoholic fermentation are the essential steps for the stimulatory action of beer on gastric acid secretion and release of gastrin; (b) carbohydrate metabolites with a molecular weight of less than 1000 are the acid-stimulatory agents in fermented beer; and (c) gastrin is the mediator of the stimulation of acid secretion because all substances that had a potent acid-stimulatory action also were potent stimuli of gastrin release.