Clinical predictors and outcomes associated with acute return of pulmonary vein conduction during pulmonary vein isolation for treatment of atrial fibrillation.

BACKGROUND: Pulmonary vein electrical isolation (PVI) is an effective treatment for atrial fibrillation (AF). However, recurrence of pulmonary vein (PV) conduction after ablation may limit long-term success. OBJECTIVE: We sought to determine the clinical predictors of acute PV reconnection during PVI and assess the long-term clinical outcomes associated with this phenomenon. METHODS: We studied all patients with AF referred for PVI between November 2000 and August 2004. Over the course of the study period, PVI of arrhythmogenic PVs was performed segmentally using a 4-mm tip (52 degrees , 40 W, up to 90 seconds) or 8-mm tip catheter (50 degrees , 70 W, up to 60 seconds). PVI was defined as entry and exit block using a multipolar Lasso catheter. All veins were resampled to confirm isolation after 20-60 minutes. AF control was defined as no AF on or off a previously ineffective antiarrhythmic drug. Follow-up data included transtelephonic monitoring and clinical data collection from patient interviews. RESULTS: There were 424 patients who underwent isolation of 1,347 PVs during the study period. Acute reconnection of at least one PV occurred in 211 (50%) of the 424 patients and 326 (24%) of 1,347 of the PVs targeted. The left superior PV was most likely to acutely recover conduction compared with the other veins (left superior 31%, right superior 26%, right inferior 22%, left inferior 24%; P = .03). Patients with acute reconnection were more likely to be older, have a larger left atrium, have a history of hypertension or obstructive sleep apnea, and demonstrate persistent AF. After a single procedure, AF control was achieved in 153 (70%) of the 213 patients who demonstrated acute PV reconnection compared with 148 (73%) of 211 patients without acute PV reconnection observed (P = .52). CONCLUSIONS: Acute return of PV conduction is common after successful PVI and is more likely to occur in older patients with nonparoxysmal AF, hypertension, a large left atrium, and sleep apnea. There was no significant difference in acute PV reconnection between the 4-mm and 8-mm tip RF catheter despite differences in power and duration of energy delivery. Furthermore, there was no effect of PV reconnection on long-term AF control after repeated disconnection was performed.     

Platelet glycoproteins IIb and IIIa as a calcium channel in liposomes

Human platelet membrane glycoproteins IIb and IIIa (GPIIb and IIIa) were incorporated into phospholipid vesicles by the reverse-phase technique to assess the ability of GPIIb and IIIa to function as a Ca2+ channel. Movement of Ca2+ across the lipid bilayer was quantitated by injection of proteoliposomes with encapsulated Fura-2 into Ca2+ buffers and measurement of Fura-2 fluorescence as an indicator of Ca2+ influx. Reciprocally, to assess the function of proteins in an inside-out orientation, Ca2+-loaded vesicles were injected into Ca2+-free buffer and Ca2+ efflux monitored by a calcium electrode. Incorporation of the IIb-IIIa complex produced significant facilitation of Ca2+ movement across the lipid bilayer. No net transmembrane Ca2+ movement was seen with dissociated IIb and IIIa. Movement of Ca2+ was proportional to the transmembrane Ca2+ gradient. Ca2+ movement into the vesicles was inversely proportional to extravesicular NaCl from 25 to 150 mmol/L, analogous to several studies in the intact platelet. Adenosine triphosphate had no effect on Ca2+ movement into or out of the vesicles. Specific inhibition of a Ca2+ shift into the vesicles was seen with M148, a monoclonal antibody to IIb/IIIa, while no inhibition was observed with a panel of other anti-IIb/IIIa monoclonal antibodies. This suggests that a specific site on the complex or orientation of the complex is essential for calcium channel function. These data demonstrate that the GPIIb/IIIa complex can serve as a passive Ca2+ channel across a phospholipid bilayer and has the potential to play a role in Ca2+ flux across the platelet plasma membrane.     

Genetic markers may predict disease behavior in patients with ulcerative colitis

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. (Gastroenterology 1997 Jun;112(6):1845-53)     

Effects of positive and negative pressure ventilation on cerebral blood volume of newborn infants

The effects of intermittent positive airway and continuous negative extrathoracic pressure ventilation on cerebral blood volume in preterm infants were studied using near infrared spectroscopy. In 12 infants continuous negative extrathoracic pressure caused a median decrease in cerebral blood volume of 0.14ml/100ml brain (95% confidence intervals (CI) 0.035–0.280) compared with no respiratory support. Oxygenated and deoxygenated haemoglobin also decreased, implying increased venous drainage as the main effect. In 17 infants intermittent positive pressure ventilation also caused a median reduction in cerebral blood volume of 0.06 ml/100 ml brain (95% CI 0.010–0.115) compared with endotracheal positive airway pressure. Deoxygenated haemoglobin increased by 0.07 ml/100 ml brain (95% CI 0.010–0.100) while oxygenated haemoglobin decreased by O.lOml/lOOml brain (95% CI 0.005–0.175). The increase in deoxygenated haemoglobin implies decreased venous drainage and the decrease in oxygenated haemoglobin implies that other factors may also be significant. Heart rate, blood pressure and oxygen saturation were monitored continuously and remained stable.