Left atrial pacing induces memory and is associated with atrial tachyarrhythmias

OBJECTIVE: Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. METHODS: A total of 12 chronically instrumented mongrel dogs in complete heart block were paced AV sequentially from the left or right atrium for 7-28 days, and then recovered in normal sinus rhythm for 21 days. Rate histograms were recorded during the entire period, and electrophysiological studies were conducted to note changes in the atrial gradient, effective refractory period and atrial rhythm. No atrial arrhythmias were seen in eight control animals that were instrumented but not paced. RESULTS: Left atrial pacing was associated with a decreased atrial gradient and occurrence of atrial tachycardias that appeared during pacing and persisted during recovery from pacing. In contrast, right atrial pacing did not alter the atrial gradient significantly. Atrial tachycardias occurring during right atrial pacing disappeared after cessation of pacing, when dogs recovered in sinus rhythm. The effective refractory period did not change in either group. CONCLUSIONS: Pacing-induced impulse initiation from the left atrium alters the atrial gradient and is associated with atrial tachycardias. These changes in atrial gradient occur in the absence of ERP changes and may be early predictors of an arrhythmogenic substrate.     

Evaluation of KCB-328, a new IKr blocking antiarrhythmic agent in pacing induced canine atrial fibrillation.

HYPOTHESIS: KCB-328 is a new potassium channel blocker, which prolongs action potential duration with exhibition of minimal reverse use dependence. We tested the efficacy and proarrhythmic potential of KCB-328, dofetilide and propafenone in the pacing induced canine model of atrial fibrillation (AF). METHODS: Mongrel dogs in complete heart block were paced for 1-6 weeks to produce AF, and given KCB-328 or dofetilide. A subset then received propafenone 14+/-3 days after testing the first drug. RESULTS: KCB-328 prolonged right and left atrial (RA and LA) activation times and AF cycle length (CL), terminating AF in 3 of 6 dogs. RA effective refractory period (ERP) and ventricular ERP and QT interval were prolonged. Dofetilide terminated AF in 1/6 dogs, and increased AF CL and ventricular ERP and QT interval. Dofetilide's reverse use dependency on the QT interval was greater than KCB-328. Propafenone prolonged RA and LA activation times and AF CL and terminated AF in 8 of 9 dogs. One death occurred with dofetilide, none with KCB-328 or propafenone. CONCLUSION: The spectrum of effect of the three drugs differed significantly: propafenone showed the greatest success in AF termination, and both propafenone and KCB-328 appeared less proarrhythmic than dofetilide in this model.     

Multicenter collaborative for orthopaedic research in India: An opportunity for global leadership

Road traffic accidents are increasing at an alarming rate and have become a major public health concern in India. In addition, there is a lack of trauma research output and reliable data from India. There are several issues and challenges that have presented an opportunity for researchers and surgeons in India to develop a collaborative aimed at improving the quality and productivity of orthopaedic trauma research. Establishing a network of surgical researchers across India is a necessary first step towards global leadership in orthopaedic surgery trials.     

A comparative study of ketanserin and metoprolol in essential hypertension

The role of serotonin in the pathogenesis of hypertension is interesting, and its investigation is much in vogue at present. This study compared the hypotensive effect of ketanserin, a specific 5-hydroxytryptamine receptor antagonist, with metoprolol in essential hypertension. On a double-blind basis, one treatment group (19 patients on ketanserin) was compared with another (21 patients on metoprolol). There was a significant reduction in diastolic blood pressure with both ketanserin and metoprolol (P less than 0,001). Side-effects were insignificant. One patient on metoprolol and 2 on ketanserin complained of dizziness. The dose of ketanserin was 40 mg twice a day and that of metoprolol 100 mg twice a day. Ketanserin does not appear to cause abnormal haematological values or biochemical adverse effects. It can be given to hypertensive patients with cardiac failure or bronchial asthma without adverse effects and may improve the peripheral vascular status of a hypertensive patient.     

Japanese Encephalitis Outbreak, India, 2005

An outbreak of viral encephalitis occurred in Gorakhpur, India, from July through November 2005. The etiologic agent was confirmed to be Japanese encephalitis virus by analyzing 326 acute-phase clinical specimens for virus-specific antibodies and viral RNA and by virus isolation. Phylogenetic analysis showed that these isolates belonged to genogroup 3.