Prevalence and prognostic significance of atrial arrhythmias after orthotopic cardiac transplantation

Objectives. We studied the duration and prognostic significance of atrial arrhythmias in the denervated transplanted heart, specifically the occurrence of atrial fibrillation in the absence of vagal modulation.

Background. Substantial animal data indicate that vagally induced dispersion of atrial refractoriness plays a central role in the induction and maintenance of atrial fibrillation.

Methods. We studied the occurrence of atrial arrhythmias in the denervated hearts of 88 consecutive orthotopic transplantations in 85 patients by means of continuous telemetry and all available electrocardiographic tracings.

Results. Fifty percent of recipients (44 of 88) developed at least one atrial arrhythmia. Atrial fibrillation occurred 23 times (21 recipients), atrial flutter 39 times (26 recipients), ectopic atrial tachycardia 3 times (3 recipients) and supraventricular tachycardia 18 times (11 recipients). The number of atrial fibrillation and atrial flutter episodes did not differ (23 vs. 39, p = 0.072), but the fibrillation (37.0 ± 10 vs. 6.6 ± 3.6 h, p = 0.014). Atrial fibrillation was associated with an increased risk of subsequent death (10 of 21 recipients with vs. 15 of 67 without atrial fibrillation, risk ratio 3.15 ± 0.18, p = 0.005 by Cox proportional hazards model). All 5 recipients who developed “late” atrial fibrillation (>2 weeks after transplantation) died versus 5 of 16 who developed atrial fibrillation within the first 2 weeks (p = 0.007). Causes of death included rejection (three recipients), allograft failure (two recipients), infection (three recipients) and multiorgan failure (two recipients). Atrial fibrillation was not associated with age, gender, ischemic time, reason for transplantation, echocardiographic variables, invasive hemodynamic variables or biopsy grade. Mean time from atrial arrhythmia to echocardiography was 2.7 ± 3.3 days; that to biopsy was 4.8 ± 6.3 days. Atrial flutter was not associated with subsequent death. Only 7 (15.9%) of 44 recipients demonstrated moderate or severe allograft rejection at the time of the arrhythmia.

Conclusions. Atrial arrhythmias occur frequently in the denervated transplanted heart, often in the absence of significant rejection. Late atrial fibrillation may be associated with an increased all-cause mortality.     

Fluids in septic shock: too much of a good thing?

In a recent issue of Critical Care, Brandt and colleagues report the effects of a 'liberal' fluid loading protocol compared to a more 'restrictive' protocol on hemodynamics and mortality in pigs in which septic shock had been induced. It appears that the former protocol was associated with higher mortality in spite of improved hemodynamics compared to the latter. The results of the paper are discussed here in view of the scope and mechanisms of these findings. With regard to fluid resuscitation, they indicate that too much of an otherwise good thing is harmful, even if overhydration and edema formation seem to have been prevented. They also do not exclude a specific toxic effect of the larger volumes of hydroxyethyl starch in the 'liberal' strategy. The precise nature of a toxic effect remains obscure, however, but may involve the kidneys.     

A pilot methodology study for the photographic assessment of post‐inflammatory hyperpigmentation in patients treated with tretinoin

Background Post‐inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. Aims A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual‐controlled methodology study that consisted of a photographic assessment protocol with facial mapping. Materials and methods The study was based on a secondary analysis of a phase 4, community‐based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III–V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. Results Despite the small number of subjects evaluated (n = 25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ = 0.84). Conclusion Further study with a larger population is recommended to validate the accuracy of this method.     

The effectiveness of adding cognitive behavioural therapy aimed at changing lifestyle to managed diabetes care for patients with type 2 diabetes: design of a randomised controlled trial

Background  

In patients with type 2 diabetes, the risk for cardiovascular disease is substantial. To achieve a more favourable risk profile, lifestyle changes on diet, physical activity and smoking status are needed. This will involve changes in behaviour, which is difficult to achieve. Cognitive behavioural therapies focussing on self-management have been shown to be effective. We have developed an intervention combining techniques of Motivational Interviewing (MI) and Problem Solving Treatment (PST). The aim of our study is to investigate if adding a combined behavioural intervention to managed care, is effective in achieving changes in lifestyle and cardiovascular risk profile.     

Relationship of mu opioid receptor binding to activation of G-proteins in specific rat brain regions

This study investigated the relationship between mu receptor binding and mu agonist activation of G-proteins in the rat brain. To directly compare agonist potencies in receptor binding (K(i) values) and G-protein activation (K(s) values), both agonist-stimulated [(35)S]guanosine-5'-O-(gamma-thio)-triphosphate ([(35)S]GTPgammaS) and [(3)H]naloxone binding assays were conducted under identical conditions, using the full mu agonist [d-Ala(2), N-Me(4), Gly(5)-ol]-enkephalin (DAMGO). DAMGO exhibited biphasic competition of [(3)H]naloxone binding and stimulation of [(35)S]GTPgammaS binding in most regions. Whereas the high-affinity component represented a large percentage (50-80%) of total receptor sites, the high-affinity component of DAMGO-stimulated [(35)S]GTPgammaS binding was much lower, <30% of the total, and in most regions significant stimulation of [(35)S]GTPgammaS binding did not occur until the high-affinity binding sites were completely occupied. Moreover, the low-affinity potencies for DAMGO in receptor binding and G-protein activation were the same across different regions. Receptor-transducer amplification factors were calculated by the ratio of the apparent B(max) of net agonist-stimulated [(35)S]GTPgammaS binding to the B(max) of receptor binding. Amplification factors for the nine regions examined were relatively high and varied significantly across regions, from a ratio of 8 in the thalamus to 38 in the cortex, suggesting that the efficiency of mu opioid receptor coupling to G-proteins varies across brain regions.