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The antiarrhythmic clofilium is an efficient blocker of hERG1 potassium channels that are strongly expressed in the heart. Therefore, derivatives of clofilium that emit positrons might be useful tools for monitoring hERG1 channels in vivo. Fluoro- clofilium (F-clofilium) was synthesized and its channel-blocking properties were determined for hERG1 and hEAG1 channels expressed in HEK?293 cells and in Xenopus oocytes. When applied extracellularly in the whole-cell patch-clamp configuration, F-cloflium exhibited a slower onset of block when compared with clofilium, presumably owing to its lower membrane permeability. When applied in the inside-out configuration at the intracellular membrane side, it blocked hEAG1 channels almost as efficiently as clofilium (IC50 1.37 nM and 0.83 nM, respectively). Similar results were obtained for hERG1, showing F-clofilium is a potent hERG1 and hEAG1 channel blocker once it has reached the intracellularly accessible target site at the channel. Using the (18)F-labeled analog we studied the in vivo binding and distribution of F-clofilium in mice and a dog. Greatest activity was found in kidneys and bones. A small but significant enrichment of activity in the dog myocardium known for its expression of cERG1 channels allowed to depict the myocardium of a living dog by PET. Thus, F-clofilium is a useful tool for imaging hERG channels in living organisms.

Background and Objectives:In the era of stents, lesion length remains an important predictor of restenosis. Drugeluting stents (DESs) have significantly reduced in-stent restenosis (ISR), but results in long lesions are still lacking. Therefore, we investigated the impact of DESs on clinical outcomes in patients with diffuse coronary lesions. Subjects and Methods: Between January 2004 and January 2005, 80 patients (94 lesions) with lesions >20 mm in length were treated with one or more DESs and underwent follow-up coronary angiography. The patients were divided into three groups: Group 1 was composed of those with lesions 21 to 35 mm in length, Group 2 was composed of those with lesions 36 to 50 mm in length, and Group 3 was composed of those with lesions ≥51 mm in length. Results: The mean clinical follow-up duration was 9 months. On the 6-month follow-up angiogram, 6.4% of the lesions had binary ISR (5.0% in group 1, 8.7% in group 2, and 9.1% in group 3). The percent diameter stenosis was 6.0±18.15% in Group 1, 12.61±21.99% in Group 2, and 19.81±31.26% in Group 3 (p< 0.05). Late lumen loss was 0.17±0.50 mm in Group 1, 0.39±0.66 mm in Group 2, and 0.59±0.93 mm in Group 3 (p<0.05). Lesion length was associated with an increase in percent diameter stenosis and late lumen loss (of 6.9% and 0.21 mm per 15 mm). Conclusion: DES implantation is considered safe and effective in the treatment of diffuse lesions. However, lesion length may be associated with an increase in percent diameter stenosis and late lumen loss at 6-month follow-up. (Korean Circ J 2008;38:612-617)

Background Inappropriate sinus tachycardia IST manifests chronic nonparoxysmal sinus tachycardia in healthy individuals and is characterized by consistently elevated heart rate and exaggerated responses to minimal physical activity. Heart rate variability HRV using 24-hour Holter monitoring represents one of the methods of evaluating the harmony of autonomic nervous system activity. So, authors investigate the autonomic nervous system activity by the HRV in patients with IST. Methods We compared the pattern of cardiac sympathetic and parasympathetic activity through the time domain analysis of heart rate variability with 24-hour Holter monitoring between 23 patients with IST and 23 healthy control subjects. None of the patients had organic heart disease as determined by routine laboratory examination and echocardiography. And then, time domain measures mean NN, SDNN, SDANN, SD, rMSSD, pNN50 were analyzed. Results The mean age of patients and control were 38 10 and 37 9 years, respectively p NS . The mean clinical heart rate of patients and control was 104 5/min and 72 5/min, respectively p 0.05 . Among the time domain indices, mean of all normal RR intervals mean NN , standard deviation of all normal RR intervals SDNN , standard deviation of mean RR interval SDANN , mean of standard deviations of all normal RR intervals SD , root mean square successive differences between adjacent normal RR intervals rMSSD , and percent of difference between adjacent normal RR intervals pNN50 in the patient group were significantly shorter compared to control group p 0.01 . Conclusion In IST, cardiac vagal influence on the heart rate is blunted. Korean Circulation J 2000 ; 30 9 : 1133-1138

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