Citations

We present the case of a patient who underwent repeated ablations for atrial fibrillation and presented with recurrent dyspnea, elevated left atrial pressure with large V waves in the absence of mitral regurgitation. This case provides an example of “stiff left atrial syndrome” as has been described in patients with mitral valve replacement and only recently in patients with radiofrequency ablations for atrial fibrillation. © 2012 Wiley Periodicals, Inc.

The Food and Drug Administration has not cleared the following medical devices for the use described in this study. The following medical devices are being discussed for an off-label use: cervical lateral mass screws. Object As an alternative for cases in which the anatomy and spatial relationship between C-2 and a vertebral artery precludes insertion of C-2 pedicle/pars or C1–2 transarticular screws, a technique that includes opposing laminar hooks (claw) at C-2 combined with C-1 lateral mass screws may be used. The biomechanical stability of this alternate technique was compared with that of a standard screw-rod technique in vitro. Methods Flexibility tests were performed in 7 specimens (occiput to C-3) in the following 6 different conditions: 1) intact; 2) after creating instability and attaching a posterior cable/graft at C1–2; 3) after removing the graft and attaching a construct comprising C-1 lateral mass screws and C-2 laminar claws; 4) after reattaching the posterior cable-graft at C1–2 (posterior hardware still in place); 5) after removing the posterior cable-graft and laminar hooks and placing C-2 pedicle screws interconnected to C-1 lateral mass screws via rod; and 6) after reattaching the posterior cable-graft at C1–2 (screw-rod construct still in place). Results All types of stabilization significantly reduced the range of motion, lax zone, and stiff zone compared with the intact condition. There was no significant biomechanical difference in terms of range of motion or lax zone between the screw-rod construct and the screw-claw-rod construct in any direction of loading. Conclusions The screw-claw-rod technique restricts motion much like the standard Harms technique, making it an acceptable alternative technique when aberrant arterial anatomy precludes the placement of C-2 pars/pedicle screws or C1–2 transarticular screws.

Functional values of LogSD of the ventilation distribution (σV̇) have been reported previously, but functional values of LogSD of the perfusion distribution (σq̇) and the coefficient of correlation between ventilation and perfusion (ρ) have not been measured in humans. Here, we report values for σV̇, σq̇, and ρ obtained from wash-in data for three gases, helium and two soluble gases, acetylene and dimethyl ether. Normal subjects inspired gas containing the test gases, and the concentrations of the gases at end-expiration during the first 10 breaths were measured with the subjects at rest and at increasing levels of exercise. The regional distribution of ventilation and perfusion was described by a bivariate log-normal distribution with parameters σV̇, σq̇, and ρ, and these parameters were evaluated by matching the values of expired gas concentrations calculated for this distribution to the measured values. Values of cardiac output and LogSD ventilation/perfusion (V̇a/Q̇) were obtained. At rest, σq̇ is high (1.08 ± 0.12). With the onset of ventilation, σq̇ decreases to 0.85 ± 0.09 but remains higher than σV̇ (0.43 ± 0.09) at all exercise levels. Rho increases to 0.87 ± 0.07, and the value of LogSD V̇a/Q̇ for light and moderate exercise is primarily the result of the difference between the magnitudes of σq̇ and σV̇. With known values for the parameters, the bivariate distribution describes the comprehensive distribution of ventilation and perfusion that underlies the distribution of the V̇a/Q̇ ratio.

α ‐Actinin2 (Actn2) is a predominant protein in the sarcomere Z disc whose mutation can lead to cardiomyopathy. However, the function of Actn2 in Z‐disc assembly and cardiomyopathy in vertebrates remains elusive. We leveraged genetic tools in zebrafish embryos to elucidate the function of Actn2. We identified a single Actn2 homologue expressed in the zebrafish heart and conducted loss‐of‐function studies by antisense morpholino technology. Although zebrafish Actn2 assembles early into the Z disc, depletion of actn2 did not affect the early steps of sarcomere assembly. Instead, Actn2 is required for Z bodies to register laterally, forming well‐aligned Z discs. Presumably as a consequence to this structural defect in the sarcomere, the depletion of Actn2 resulted in reduced cardiac function, primarily characterized as a reduced end‐diastolic diameter. The depletion of actn2 also significantly reduced the ventricle chamber size, due to both reduced cardiomyocyte (CM) size and CM number. Interestingly, reduced CM size can be rescued by the cessation of heart contractions. The genetic studies of zebrafish uncovered a function for actn2 in lateral registration of Z body. In actn2 morphant fish, the Z ‐disc defect sequentially affects cardiac function, which leads to morphological changes in the ventricle through a mechanical force‐dependent mechanism.—Yang, J., Xu, X. α ‐Actinin2 is required for the lateral alignment of Z discs and ventricular chamber enlargement during zebrafish cardiogenesis. FASEB J. 26, 4230–4242 (2012). www.fasebj.org

Abstract As immune responses likely contribute to degeneration of bioprosthetic heart valves (BHVs), this nonhuman primate study compares the anti-Gal antibody response to BHVs from wild type (WT) pigs (current BHVs) and those from α-galactosyltransferase knockout (GTKO) pigs. Stented glutaraldehyde fixed BHVs from WT (n=4) and GTKO (n=3) pigs were commercially manufactured and implanted in the mitral position in nonhuman primates using standard surgical techniques. Recipients were treated with Lovenox (1mg/kg BID) for 5 weeks reducing to 1mg/kg daily for one week and then discontinued. Recipients were sensitized to the αGal antigen by immunization to match IgG levels found in humans. Serum antibody responses were monitored by ELISA. WT BHVs were explanted at 3 hours, 1 year, 2 years and the fourth is currently ongoing at 3 years. One GTKO BHV was explanted at 218 days. The remaining two GTKO BHVs are currently ongoing at 3 years. After immunization, circulating anti-Gal IgG levels were comparable in both groups at the time of implantation and were equal or greater than human levels. Anti-Gal antibody levels decreased in both WT and GTKO recipients after implantation. WT recipients, however, retained elevated levels (greater than 20% preimplant values) of anti-Gal IgG for at least the first year post implant. Conversely anti-Gal IgG levels in all GTKO recipients fell within one month and remained at less than 20% preimplant values. Analysis of the area under the curve showed a significant increase of anti-Gal IgG in the WT BHV group compared to GTKO BHV recipients (p<0.01). In this nonhuman primate model, the persistently and significantly (p<0.01) elevated levels of anti-Gal IgG antibody observed in WT but not GTKO BHV recipients, indicate continuing immune stimulation to the αGal antigen. Current commercially available BHVs are similarly known to contain αGal antigen. Anti-Gal antibody has been shown to increase calcification of processed pericardium in the rat implant model. These data support the hypothesis that preformed and induced anti-Gal antibody in BHV recipients may initiate an early immune response, which promotes subsequent calcification. BHVs made from GTKO pigs would eliminate this major xenoreactive antigen and provide a prosthesis with reduced immunogenicity. Such BHVs made from GTKO pigs may have greater durability and be potentially used in younger patients with more active immune systems.

Neural cells derived from induced pluripotent stem cells from patients with genetic forms of Parkinson’s disease provide insights into disease pathogenesis.