Emergency treatment of tachyarrhythmias

The diagnosis, clinical aspects, and emergency treatment of the most common cardiac arrhythmias, including atrial flutter and fibrillation, paroxysmal supraventricular tachycardia, the Wolff-Parkinson-White syndrome, ventricular tachycardia, and torsades de pointes, are discussed. The use of the antiarrhythmic drugs most frequently utilized in clinical practice is described.     

The role of Holter monitoring in patients with recurrent sustained ventricular tachycardia: an electrophysiologic correlation

The significance of spontaneous ventricular premature depolarization (VPD) frequency and severity in patients with sustained ventricular tachycardia undergoing serial electrophysiologic studies (EPS) are unknown. Nineteen patients with sustained ventricular tachycardia were studied with 24-hour Holter recordings prior to control EPS and prior to each drug trial. Successful drug or surgical treatment (with the exception of amiodarone) was based upon noninducibility of ventricular tachycardia in the laboratory. Among the eight noninducible and nonamiodarone medically treated patients, two (25%) had significant VPD reduction and/or Lown class improvement. The remaining six (75%) had no change or worsening of Holter findings, despite noninducibility of sustained VT. Among the six amiodarone-treated patients, five of whom were persistently inducible prior to discharge, four (66%) had improved and two (33%) had worsened Holter findings compared to control. None of the five (100%) surgically managed patients were inducible postoperatively, and three of the five (60%) had no change or worsening of Holter findings. We conclude that (1) EPS are superior to Holter findings in assessing successful management; and (2) Holter findings may be concordant or discordant during EPS serial drug trials or following surgery and therefore cannot predict the success or failure of the intervention.     

Effect of tecarfarin,a novel vitamin K epoxide reductase inhibitor,on coagulation in beagle dogs

Background and purpose:

Tecarfarin (ATI-5923) is a novel vitamin K epoxide reductase inhibitor that is metabolized by esterase (mainly human carboxylesterase 2) to a single major metabolite, ATI-5900, in rats, dogs and humans. Tecarfarin is not significantly metabolized by CYP450 enzymes. The objective of this study was to test and compare the efficacy of tecarfarin with that of warfarin, when administered either intravenously or once a day orally, to produce stable anticoagulation in beagle dogs.

Experimental approach:

Effects on coagulation were assessed by measuring the activity levels of Factor VII and Factor X and thromboplastin-induced coagulation times, reported as prothrombin time (PT).

Key results:

Continuous intravenous infusions and oral administration of tecarfarin and warfarin caused a dose-dependent decrease in activity of Factor VII and Factor X, and associated increase in PT. Intravenous fresh frozen canine plasma or subcutaneous vitamin K₁ treatment reversed the anticoagulant effects of orally administered tecarfarin. Consistent with the inhibitory effects of amiodarone on CYP2C9, co-administration of amiodarone significantly increased the anticoagulation effect of warfarin and plasma warfarin concentrations. In contrast, amiodarone had no effect on the anticoagulation induced by tecarfarin or tecarfarin plasma concentrations in this model.

Conclusions and implications:

Overall, the data presented herein indicate that tecarfarin, via a vitamin K-dependent mechanism, causes changes in key parameters of haemostasis in beagle dogs that are consistent with effective anticoagulation. Compared to warfarin it has a decreased potential to interact metabolically with drugs that inhibit CYP450 enzymes and, therefore, may offer an improved safety profile for patients.     

Changes in physical health among participants in a multidisciplinary health programme for long-term unemployed persons

Background  

The relationship between poor health and unemployment is well established. Health promotion among unemployed persons may improve their health. The aims of this study were to investigate characteristics of non-participants and drop-outs in a multidisciplinary health promotion programme for long-term unemployed persons with health complaints, to evaluate changes in physical health among participants, and to investigate determinants of improvement in physical health.     

Maintenance of reduction of pediatric distal radius fractures with a sugar-tong splint

Distal radius fractures are common injuries in children. Displaced fractures have traditionally been treated with closed reduction followed by immobilization in a long arm cast. Because of variable success rates with this technique, a trend in the literature is toward operative fixation of these fractures. A popular alternative practice involves temporary immobilization in a sugar-tong splint, though we are unaware of any studies demonstrating the efficacy of this technique in children. We present our experience in treating these injuries initially with a sugar-tong splint and then with a short arm cast. We retrospectively reviewed the cases of 53 patients (age range, 2-12 years) treated with closed reduction and a sugar-tong splint followed by conversion to a short arm cast after 2 to 3 weeks. In 51 (96%) of 53 fractures, reduction was maintained without more aggressive intervention. The sugar-tong splint is effective in maintaining reductions in pediatric distal radius fractures and has none of the added risks associated with current alternative methods.     

Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual

Bone mass accrual is a major determinant of skeletal mass, governed by bone remodeling, which consists of bone resorption by osteoclasts and bone formation by osteoblasts. Bone mass accrual is inhibited by sympathetic signaling centrally regulated through activation of receptors for serotonin, leptin, and ACh. However, skeletal activity of the parasympathetic nervous system (PSNS) has not been reported at the bone level. Here we report skeletal immune-positive fibers for the PSNS marker vesicular ACh transporter (VAChT). Pseudorabies virus inoculated into the distal femoral metaphysis is identifiable in the sacral intermediolateral cell column and central autonomic nucleus, demonstrating PSNS femoral innervation originating in the spinal cord. The PSNS neurotransmitter ACh targets nicotinic (nAChRs), but not muscarinic receptors in bone cells, affecting mainly osteoclasts. nAChR agonists up-regulate osteoclast apoptosis and restrain bone resorption. Mice deficient of the α₂nAChR subunit have increased bone resorption and low bone mass. Silencing of the IL-1 receptor signaling in the central nervous system by brain-specific overexpression of the human IL-1 receptor antagonist (hIL1ra_Ast^+/+ mice) leads to very low skeletal VAChT expression and ACh levels. These mice also exhibit increased bone resorption and low bone mass. In WT but not in hIL1ra_Ast^+/+ mice, the cholinergic ACh esterase inhibitor pyridostigmine increases ACh levels and bone mass apparently by inhibiting bone resorption. Taken together, these results identify a previously unexplored key central IL-1–parasympathetic–bone axis that antagonizes the skeletal sympathetic tone, thus potently favoring bone mass accrual.