Background-Structural and electrophysiological changes of the atria occur with prolonged rapid rates; however, the effects of sustained atrial fibrillation (AF) on autonomic innervation of the atria are unknown. We hypothesized that electrophysiological remodeling from rapid atrial rates is accompanied by altered atrial autonomic innervation. Methods and Results-Six dogs (paced group) underwent atrial pacing at 600 bpm; 9 dogs (control animals) were not paced. All paced dogs developed sustained AF by week 4 of pacing. All 15 animals underwent positron emission tomography imaging of the atria with [C-11] hydroxyephedrine (HED) to label sympathetic nerve terminals. HED retention in the atria was significantly greater in paced dogs compared with control animals (Pϭ0.03). Tissue samples from the atrial appendages had a greater concentration of norepinephrine in paced animals than in control animals (Pϭ0.01). The coefficient of variation of HED retention was also greater in paced animals (Pϭ0.05) and was greater in the right atrium than in the left atrium (Pϭ0.004). Epicardial activation maps of AF were obtained in the paced animals at baseline and with autonomic manipulation. Mean AF cycle length was longer in the right atrium (109.2Ϯ5 ms) than in the left atrium (85.8Ϯ5.5 ms) at baseline (Pϭ0.005). AF cycle length did not vary significantly from baseline (97.6Ϯ13.4 ms) with stellate stimulation (100.5Ϯ6 ms) but lengthened with propranolol (107.5Ϯ6.1 ms, Pϭ0.03). Conclusions-Rapid rates of AF produce a heterogeneous increase in atrial sympathetic innervation. These changes parallel disparate effects of rapid pacing-induced AF on atrial electrophysiology.

Background-Heterogeneous electrophysiological properties, which may be due in part to autonomic innervation, are important in the maintenance of atrial fibrillation (AF). We hypothesized that heterogeneous sympathetic denervation with phenol would create a milieu for sustained AF. Methods and Results-After the determination of baseline inducibility, 15 dogs underwent atrial epicardial phenol application and 11 underwent a sham procedure. After 2 weeks of recovery, the animals had repeat attempts at inducing AF and effective refractory period (ERP) testing. Epicardial maps were obtained to determine local AF cycle lengths. ERPs were determined at baseline and during sympathetic, vagal, and simultaneous vagal/sympathetic stimulation.

[11C]Methyl‐CGS 27023A (1a) and its analogs [11C]methyl‐2‐picolyl‐CGS 27023A (1b), [11C]methyl‐benzyl‐CGS 27023A (1c), [11C]methyl‐2‐nitro‐CGS 27023A (1d), [11C]methyl‐3‐nitro‐CGS 27023A (1e), and [11C]methyl‐4‐nitro‐CGS 27023A (1f), novel radiolabeled matrix metalloproteinase (MMP) inhibitors, have been synthesized for evaluation as new potential positron emission tomography (PET) breast cancer imaging agents. The appropriate precursors for radiolabeling were obtained in four to five steps from starting material amino acid D‐valine with moderate to excellent chemical yields. Precursors were labeled by [11C]methyl triflate through 11C–O‐methylation method at the aminohydroxyl position under basic conditions and isolated by solid‐phase extraction (SPE) purification to produce pure target compounds in 40–60% radiochemical yields (decay corrected to end of bombardment), in 20–25 min synthesis time. Copyright © 2002 John Wiley & Sons, Ltd.

Breast cancer is the most commonly diagnosed cancer of women and the second leading cause of cancer deaths among women. Experiments in animal models of breast cancer have shown that matrix metalloproteinase (MMP) inhibitors can significantly reduce the growth rate of both primary and secondary tumors and can block the process of metastasis.(l) MMPs are

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Background-Liquid-filled balloons for coronary brachytherapy provide significant advantages over solid sources in dose homogeneity but carry the risk of life-threatening radiointoxication after balloon rupture and laboratory contamination in case of a spill. We hypothesized that the positron emitter 68 Ga, with a half-life of only 68 minutes, was well suited to overcome these safety obstacles while providing full therapeutic efficacy. Methods and Results-The feasibility, efficacy, and safety of 68 Ga liquid-filled balloon brachytherapy were investigated in the porcine coronary overstretch model. Four groups of 5 balloon-induced coronary lesions were irradiated with 8, 12, 16, and 24 Gy targeted to the adventitia. Ten unirradiated lesions served as controls. Segments treated with 16 or 24 Gy exhibited marked suppression of neointimal proliferation at 28-day follow-up, with quantitative parameters of intraluminal proliferation reduced to Ͻ20%. This beneficial effect was not compromised by untoward edge effects. Uninjured but irradiated vessels did not show histological signs of radiation damage. The 68 Ga whole-body dose due to balloon rupture was estimated to be 5 rem/50 mCi treatment activity and compared favorably with that of 188 Re (78 rem/50 mCi). Conclusions-68 Ga positron radiation suppresses neointimal proliferation at doses of 16 and 24 Gy. This biological efficacy, coupled with the attractive safety profile, suggests the selection of 68 Ga as an attractive isotope for liquid-filled balloon brachytherapy.

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