Does flecainide regain its antiarrhythmic activity after electrical cardioversion of persistent atrial fibrillation?

OBJECTIVES: The purpose of this study was to evaluate the hypothesis that presumed reversion of electrical remodeling after cardioversion of atrial fibrillation (AF) restores the efficacy of flecainide. BACKGROUND: Flecainide loses its efficacy to cardiovert when AF has been present for more than 24 hours. Most probably, the loss is caused by atrial electrical remodeling. Studies suggest electrical remodeling is completely reversible within 4 days after restoration of sinus rhythm (SR). METHODS: One hundred eighty-one patients with persistent AF (median duration 3 months) were included in this prospective study. After failure of pharmacologic cardioversion by flecainide 2 mg/kg IV (maximum 150 mg in 10 minutes) and subsequent successful electrical cardioversion, we performed intense transtelephonic rhythm monitoring three times daily for 1 month. In case of AF recurrence, a second cardioversion by flecainide was attempted as soon as possible. RESULTS: AF recurred in 123 patients (68%). Successful cardioversion by flecainide occurred only when SR had been maintained for more than 4 days (7/51 patients [14%]). Failure to cardiovert was associated with a prolonged duration of the recurrent AF episode and concurrent digoxin use. Multivariate logistic regression confirmed that successful cardioversion was determined by digoxin use (odds ratio [OR] 0.093, P = .047) and by the interaction between the duration of SR and the (inverse) duration of recurrent AF (OR 6.499, P < .001). When flecainide was administered within 10 hours after AF onset and the duration of SR was greater than 4 days, the success rate was 58%. CONCLUSIONS: Flecainide recovers its antiarrhythmic action after cardioversion of AF. However, successful pharmacologic cardioversion occurs only after SR has lasted at least 4 days and is expected only for recurrences having duration of a few hours. Immediate pharmacologic cardioversion of AF recurrence may be a worthwhile strategy for management of persistent AF.     

Ten-year heart transplantation experience at the MARITIME HEART CENTER: does volume affect results?

OBJECTIVE: To evaluate the experience of a small volume Canadian heart transplantation centre. DESIGN: Ninety-four consecutive primary heart transplants were performed from 1988 to 1998 at the Maritime Heart Center, Halifax, Nova Scotia, with 100% follow-up. Kaplan-Meier survival analysis was used. RESULTS: The mean recipient age was 48.5+/-12.3 years and donor age 33+/-13.2 years. Eighty per cent of recipients were men. The prevalence of elevated pulmonary vascular resistance (4 or more Wood units) was 20.2%. Etiology of heart failure was ischemic cardiomyopathy (50%), dilated cardiomyopathy (40.9%) and congenital heart disease (9.1%). Survival was 85.9% at one year (n=71), 75.3% at five years (n=33) and 60.5% at eight years (n=8). There was a trend toward survival benefit with human leukocyte antigen (HLA) -DR matching, body mass index ratio of donor to recipient greater than 0.8, ischemic time less than 90 mins and male donors. There was no effect on survival with donor or recipient age, recipient sex, diabetes, hypertension, hypercholesterolemia, elevated pulmonary vascular resistance and HLA-A/B mismatch. CONCLUSIONS: Excellent survival at one and five years following heart transplantation is reported that compares favourably with results published by the International Society for Heart and Lung Transplantation.     

Tracelink: A model of consolidation and amnesia

A connectionist model is presented, the TraceLink model, that implements an autonomous “off-line” consolidation process. The model consists of three subsystems: (1) a trace system (neocortex), (2) a link system (hippocampus and adjacent regions), and (3) a modulatory system (basal forebrain and other areas). The model is able to account for many of the characteristics of anterograde and retrograde amnesia, including Ribot gradients, transient global amnesia, patterns of shrinkage of retrograde amnesia, and correlations between anterograde and retrograde amnesia or the absence thereof (e.g., in isolated retrograde amnesia). In addition, it produces normal forgetting curves and can exhibit permastore. It also offers an explanation for the advantages of learning under high arousal for long-term retention.     

Dendritic cells process synthetic long peptides better than whole protein,improving antigen presentation and T‐cell activation

The efficiency of antigen (Ag) processing by dendritic cells (DCs) is vital for the strength of the ensuing T‐cell responses. Previously, we and others have shown that in comparison to protein vaccines, vaccination with synthetic long peptides (SLPs) has shown more promising (pre‐)clinical results. Here, we studied the unknown mechanisms underlying the observed vaccine efficacy of SLPs. We report an in vitro processing analysis of SLPs for MHC class I and class II presentation by murine DCs and human monocyte‐derived DCs. Compared to protein, SLPs were rapidly and much more efficiently processed by DCs, resulting in an increased presentation to CD4⁺ and CD8⁺ T cells. The mechanism of access to MHC class I loading appeared to differ between the two forms of Ag. Whereas whole soluble protein Ag ended up largely in endolysosomes, SLPs were detected very rapidly outside the endolysosomes after internalization by DCs, followed by proteasome‐ and transporter associated with Ag processing‐dependent MHC class I presentation. Compared to the slower processing route taken by whole protein Ags, our results indicate that the efficient internalization of SLPs, accomplished by DCs but not by B or T cells and characterized by a different and faster intracellular routing, leads to enhanced CD8⁺ T‐cell activation.     

Does more than a single chest tube for mediastinal drainage affect outcomes after cardiac surgery?

Background

The use of 1 or more mediastinal chest tubes has traditionally been routine for all cardiac surgery procedures to deal with bleeding. However, it remains unproven whether multiple chest tubes offer a benefit over a single chest tube.

Methods

All consecutive patients undergoing cardiac surgery (2005–2010) received at least 1 chest tube at the time of surgery based on surgeon preference. Patients were grouped into those receiving a single chest tube (SCT) and those receiving multiple chest tubes (MCT). The primary outcome was return to the operating room for bleeding or tamponade.

Results

A total of 5698 consecutive patients were assigned to 2 groups: 3045 to the SCT and 2653 to the MCT group. Patients in the SCT group were older, more often female and less likely to undergo isolated coronary artery bypass graft than those in the MCT group. Unadjusted outcomes for SCT and MCT, respectively, were return to the operating room for bleeding or tamponade (4.7% v. 5.0%; p = 0.50), intensive care unit stay longer than 48 hours (25.5% v. 27.9%; p = 0.041, postoperative stay > 9 days (31.5% v. 33.1%; p = 0.20) and mortality (3.8% v. 4.6%; p = 0.16). Logistic regression analysis, adjusted for clinical differences between groups, showed that the number of chest tubes was not associated with return to the operating room for bleeding or tamponade.

Conclusion

The use of multiple mediastinal chest tubes after cardiac surgery confers no advantage over a single chest tube in preventing return to the operating room for bleeding or tamponade.     

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

Excessive sodium intake is associated with both hypertension and an increased risk of cardiovascular events, presumably because of an increase in extracellular volume. The extent to which sodium intake affects extracellular volume and BP varies considerably among individuals, discriminating subjects who are salt-sensitive from those who are salt-resistant. Recent experiments have shown that, other than regulation by the kidney, sodium homeostasis is also regulated by negatively charged glycosaminoglycans in the skin interstitium, where sodium is bound to glycosaminoglycans without commensurate effects on extracellular volume. The endothelial surface layer is a dynamic layer on the luminal side of the endothelium that is in continuous exchange with flowing blood. Because negatively charged glycosaminoglycans are abundantly present in this layer, it may act as an intravascular buffer compartment that allows sodium to be transiently stored. This review focuses on the putative role of the endothelial surface layer as a contributor to salt sensitivity, the consequences of a perturbed endothelial surface layer on sodium homeostasis, and the endothelial surface layer as a possible target for the treatment of hypertension and an expanded extracellular volume.     

Bilateral occurrence of pheochromocytoma in patients with the multiple endocrine neoplasia syndrome type 2A (Sipple's syndrome)

Two kindreds with the multiple endocrine neoplasia type 2A syndrome were studied. Of one of these we examined 150 members, 20 of whom were treated with thyroidectomy for medullary carcinoma and nine with bilateral adrenalectomy for pheochromocytoma. Of the second kindred 59 members were examined, seven of whom were thyroidectomized and seven treated with bilateral adrenalectomy. Pheochromocytomas were invariably found on both sides, even in four cases in which the adrenals on one side appeared to be completely normal, not only at preoperative roentgenologic examination but also on inspection during the operation. The microscopic finding of micronodules and a cluster of abnormal medullary cells identical with those found in pheochromocytomas in one of the apparently normal adrenals represents a first stage in the development of diffuse medullary hyperplasia as well as nodular hyperplasia. This is in accordance with the fact that in the MEN type 2A syndrome pheochromocytomas are always multicentric and multiple in origin. On the basis of these findings we conclude that all patients with the MEN 2A syndrome who show symptoms and signs of active pheochromocytoma should be subjected to bilateral adrenalectomy, even when one or both of the adrenals appear to be normal at roentgenologic investigation.     

Longitudinal Study of Extended-Spectrum-β-Lactamase- and AmpC-Producing Enterobacteriaceae in Household Dogs

A longitudinal study was performed to (i) investigate the continuity of shedding of extended-spectrum-beta-lactamase (ESBL)-producing Enterobacteriaceae in dogs without clinical signs, (ii) identify dominant plasmid-mediated ESBL genes, and (iii) quantify ESBL-producing Enterobacteriaceae in feces. Fecal samples from 38 dogs were collected monthly for 6 months. Additional samples were collected from 7 included dogs on a weekly basis for 6 weeks. Numbers of CFU per gram of feces for non-wild-type Enterobacteriaceae were determined by using MacConkey agar supplemented with 1 mg/liter cefotaxime (MCC), and those for total Enterobacteriaceae were determined by using MacConkey agar. Cefotaxime-resistant isolates were screened by PCR and sequence analysis for the presence of bla_CTX-M, bla_CMY, bla_SHV, bla_OXA, and bla_TEM gene families. Bacterial species were identified by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis. PCR-negative isolates were tested by a double-disk synergy test for enhanced AmpC expression. A total of 259 samples were screened, and 126 samples were culture positive on MCC, resulting in 352 isolates, 327 of which were Escherichia coli. Nine dogs were continuously positive during this study, and 6 dogs were continuously negative. Monthly or weekly shifts in fecal shedding were observed for 23 dogs. Genotyping showed a large variety of ESBL genes and gene combinations at single and multiple consecutive sampling moments. The ESBL genes bla_CTX-M-1, bla_CTX-M-14, bla_CTX-M-15, bla_SHV-12, and bla_CMY-2 were most frequently found. The mean number of CFU of non-wild-type Enterobacteriaceae was 6.11 × 10⁸ CFU/g feces. This study showed an abundance of ESBL-producing Enterobacteriaceae in dogs in the Netherlands, mostly in high concentrations. Fecal shedding was shown to be highly dynamic over time, which is important to consider when studying ESBL epidemiology.