Publications

BACKGROUND

We previously showed that canine models of atrial fibrillation (AF) have different substrates (either structural or electrical) that lead to differences in AF characteristics.

OBJECTIVE

The purpose of this study was to determine whether the differences in AF characteristics also would lead to differences in atrial defibrillation thresholds (ADFTs).

METHODS

Dogs were divided into five groups: control; MR-mitral regurgitation for 5 weeks; CHF-congestive heart failure for 4 weeks; RAP-rapid atrial pacing for 6 weeks; and METH-acetyl-beta-methylcholine acutely administered. A cross-sectional area of the left atrium was calculated, and AF was induced with rapid atrial pacing. Biphasic shocks with a pulse width of 3/3 ms were delivered through specially constructed shocking catheters with a surface area of 3.7 cm(2) that were placed in the right and left atria. An up-down-up protocol was used to determine the 50% ADFT threshold (ADFT(50)). A wide-bipole AF signal was digitally filtered, and a fast Fourier transform was calculated over a 2-second window every 1 second. The dominant frequency was determined, and the organization index was calculated as the ratio of the area under the dominant peak and its harmonics to the total area of the spectrum.

RESULTS

For left atrial size, the CHF and MR groups had a significantly larger atria than did control. ADFT(50) for control, MR, CHF, RAP, and METH groups were 160 +/- 30 V, 120 +/- 50 V, 132 +/- 20 V, 668 +/- 205 V, and 593 +/- 128 V, respectively (analysis of variance, P <.0001). Dominant frequencies were significantly higher and organization indexes significantly lower in the RAP and METH models compared with the other models.

CONCLUSION

RAP and METH canine models had a significantly higher ADFT(50) compared with the other AF models. The increase in ADFT(50) in these models corresponded with higher global dominant frequencies and lower measured organization indexes.

To characterize predictors of isolated hepatitis B core antibody (anti-HBc) among human immunodeficiency virus (HIV)-infected and HIV-uninfected women, we compared 702 women with anti-HBc and hepatitis B surface antibody (anti-HBs) with 490 women with isolated anti-HBc (1.8% of whom had detectable hepatitis B virus [HBV] DNA). Factors independently associated with isolated anti-HBc without viremia were detectable hepatitis C virus (HCV) RNA, HIV positivity, history of injection drug use, >10 lifetime sex partners, and HIV RNA level >100,000 copies/mL. Anti-HBs levels were lower among anti-HCV-positive women. Isolated anti-HBc was rarely explained by occult HBV in this cohort but may be explained by the influence of viral coinfections on anti-HBs level or durability.

Changes in extracellular [Ca2+] modulate the function of bone cells in vitro via the extracellular Ca2+-sensing receptor (CaR). Within bone microenvironments, resorption increases extracellular [Ca2+] locally. To determine whether enhanced CaR signaling could modulate remodeling and thereby bone mass in vivo, we generated transgenic mice with a constitutively active mutant CaR (Act-CaR) targeted to their mature osteoblasts by the 3.5 kb osteocalcin promoter. Longitudinal microcomputed tomography of cancellous bone revealed reduced bone volume and density, accompanied by a diminished trabecular network, in the Act-CaR mice. The bone loss was secondary to an increased number and activity of osteoclasts, demonstrated by histomorphometry of secondary spongiosa. Histomorphometry, conversely, indicates that bone formation rates were unchanged in the transgenic mice. Constitutive signaling of the CaR in mature osteoblasts resulted in increased expression of RANK-L (receptor activator of nuclear factor-kappaB ligand), the major stimulator of osteoclast differentiation and activation, which is the likely underlying mechanism for the bone loss. The phenotype of Act-CaR mice is not attributable to systemic changes in serum [Ca2+] or PTH levels. We provide the first in vivo evidence that increased signaling by the CaR in mature osteoblasts can enhance bone resorption and further propose that fluctuations in the [Ca2+] within the bone microenvironment may modulate remodeling via the CaR.