Effect of repetitive brief episodes of ischemia on cell volume, electrolytes and ultrastructure

The effects of repeated brief episodes of ischemia on myocardial cell volume, electrolytes and ultrastructure were studied in dogs. Seventeen animals were divided into five groups. Group 1 underwent a single 10 minute occlusion of the circumflex coronary artery, with no subsequent reperfusion. Group 2 was similarly subjected to a 10 minute coronary occlusion, but was allowed a 20 minute reperfusion period. Group 3 underwent two 10 minute occlusions separated by 20 minutes of reperfusion and Group 4 underwent four 10 minute occlusions, each separated from the next by 20 minutes of reperfusion. Group 5 was subjected to a single, uninterrupted 40 minute occlusion.The anterior and posterior papillary muscles in each heart were sampled to compare nonischemic versus ischemic myocardium. No changes in myocardial water or electrolytes occurred during ischemia. However, reperfusion was associated with slight increases in tissue water and potassium, loss of magnesium and minimal changes in sodium or calcium ions. Electron microscopic analysis revealed signs of mild ischemic injury (absence of normal intramitochondrial granules, partial loss of glycogen and slight clumping of the nuclear chromatin) in posterior papillary muscle from Groups 1, 3 and 4. Group 2 showed complete recovery with 20 minutes of reperfusion, whereas Group 5 showed evidence of irreversible injury. There was no difference in the appearance of myocardium that had been subjected to one, two or four 10 minute occlusions. It is concluded that intermittent periods of reperfusion between brief episodes of coronary ischemia have a protective effect and prevent a cumulative deterioration of myocardial ultrastructure

Protection of ischemic myocardium in dogs using intracoronary 2,3-butanedione monoxime (BDM)

Abstract Background. -Actomyosin ATPase is one of the major ATP consuming enzymes in the myocardium. We tested whether 2,3-butanedione monoxime (BDM), a reversible inhibitor of actomyosin ATPase, given before coronary occlusion, limits infarct size in anesthetized open-chest dogs. Methods and results. -After circumflex artery catheterization using fluoroscopic guidance, BDM (125 mM) or buffer vehicle was infused (12.0 ml/min) for 20 min (BDM-20, n = 5 and Buffer-20, n = 6) or for 5 min (BDM-5, n = 6 and Buffer-5, n = 6) prior to 60 min of ischemia and 3 h of reperfusion. BDM administration increased subendocardial blood flow 271% above baseline flow (radioactive microspheres), and systolic wall thickening was converted to wall bulging (wall thickening by sonomicrometry was -27 ± 29% and -22 ± 13% of baseline in BDM-20 and BDM-5, respectively). Adjusted mean infarct size (% area-at-risk) was 11.0 ± 2.8% and 11.9 ± 2.6% in BDM-20 and BDM-5 vs. 20.2 ± 2.5% and 20.5 ± 2.5% in Buffer-20 and Buffer-5 (ancova, P < 0.05 for each BDM vs. Buffer group). Measurement of glycolytic metabolites and the adenine nucleotide pool of myocardium paced electronically at 150 beats per minute during total ischemia at 37°C following BDM showed a metabolic response similar to that seen in ischemic preconditioning. ATP depletion, nucleoside production, and lactate accumulation were slowed in ischemic tissue treated with BDM. Conclusion. -BDM given before the onset of ischemia markedly limited infarct size and reduced energy demand after the onset of ischemia. The explanation for the reduced infarct size induced by BDM treatment is hypothesized to be the persistent reduction in energy demand found in ischemic BDM treated myocardium

Eight gamma-ray pulsars discovered in blind frequency searches of Fermi LAT data

We report the discovery of eight gamma-ray pulsars in blind frequency searches using the LAT, onboard the Fermi Gamma-ray Space Telescope. Five of the eight pulsars are young (tau_c10^36 erg/s), and located within the Galactic plane (|b|<3 deg). The remaining three are older, less energetic, and located off the plane. Five pulsars are associated with sources included in the LAT bright gamma-ray source list, but only one, PSR J1413-6205, is clearly associated with an EGRET source. PSR J1023-5746 has the smallest characteristic age (tau_c=4.6 kyr) and is the most energetic (Edot=1.1E37 erg/s) of all gamma-ray pulsars discovered so far in blind searches. PSRs J1957+5033 and J2055+25 have the largest characteristic ages (tau_c~1 Myr) and are the least energetic (Edot~5E33 erg/s) of the newly-discovered pulsars. We present the timing models, light curves, and detailed spectral parameters of the new pulsars. We used recent XMM observations to identify the counterpart of PSR J2055+25 as XMMU J205549.4+253959. In addition, publicly available archival Chandra X-ray data allowed us to identify the likely counterpart of PSR J1023-5746 as a faint, highly absorbed source, CXOU J102302.8-574606. The large X-ray absorption indicates that this could be among the most distant gamma-ray pulsars detected so far. PSR J1023-5746 is positionally coincident with the TeV source HESS J1023-575, located near the young stellar cluster Westerlund 2, while PSR J1954+2836 is coincident with a 4.3 sigma excess reported by Milagro at a median energy of 35 TeV. Deep radio follow-up observations of the eight pulsars resulted in no detections of pulsations and upper limits comparable to the faintest known radio pulsars, indicating that these can be included among the growing population of radio-quiet pulsars in our Galaxy being uncovered by the LAT, and currently numbering more than 20.Comment: Submitted to Ap

Fermi Large Area Telescope Observations of Gamma-ray Pulsars PSR J1057-5226, J1709-4429, and J1952+3252

The Fermi Large Area Telescope (LAT) data have confirmed the pulsed emission from all six high-confidence gamma-ray pulsars previously known from the EGRET observations. We report results obtained from the analysis of 13 months of LAT data for three of these pulsars (PSR J1057-5226, PSR J1709-4429, and PSR J1952+3252) each of which had some unique feature among the EGRET pulsars. The excellent sensitivity of LAT allows more detailed analysis of the evolution of the pulse profile with energy and also of the variation of the spectral shape with phase. We measure the cutoff energy of the pulsed emission from these pulsars for the first time and provide a more complete picture of the emission mechanism. The results confirm some, but not all, of the features seen in the EGRET data.Comment: Accepted for publication in ApJ. 45 pages, 12 figures, 11 tables. Corresponding authors: O. Celik, F. Gargano, T. Reposeur, D.J. Thompso

Fermi-LAT Search for Pulsar Wind Nebulae around gamma-ray Pulsars

The high sensitivity of the Fermi-LAT (Large Area Telescope) offers the first opportunity to study faint and extended GeV sources such as pulsar wind nebulae (PWNe). After one year of observation the LAT detected and identified three pulsar wind nebulae: the Crab Nebula, Vela-X and the PWN inside MSH 15-52. In the meantime, the list of LAT detected pulsars increased steadily. These pulsars are characterized by high energy loss rates from ~3 \times 10^{33} erg s$^{-1}$ to 5 \times 10$^{38}$ erg s$^{-1}$ and are therefore likely to power a PWN. This paper summarizes the search for PWNe in the off-pulse windows of 54 LAT-detected pulsars using 16 months of survey observations. Ten sources show significant emission, seven of these likely being of magnetospheric origin. The detection of significant emission in the off-pulse interval offers new constraints on the gamma-ray emitting regions in pulsar magnetospheres. The three other sources with significant emission are the Crab Nebula, Vela-X and a new pulsar wind nebula candidate associated with the LAT pulsar PSR J1023-5746, coincident with the TeV source HESS J1023-575. We further explore the association between the H.E.S.S. and the Fermi source by modeling its spectral energy distribution. Flux upper limits derived for the 44 remaining sources are used to provide new constraints on famous PWNe that have been detected at keV and/or TeV energies.Comment: Accepted for publication in Astrophysical Journal, 42 pages, 17 figure

Detection of the energetic pulsar PSR B1509-58 and its pulsar wind nebula in MSH 15-52 using the Fermi-Large Area Telescope

We report the detection of high energy gamma-ray emission from the young and energetic pulsar PSR B1509$-$58 and its pulsar wind nebula (PWN) in the composite supernova remnant SNR G320.4-1.2 (aka MSH 15-52). Using 1 year of survey data with the Fermi-Large Area Telescope (LAT), we detected pulsations from PSR B1509-58 up to 1 GeV and extended gamma-ray emission above 1 GeV spatially coincident with the PWN. The pulsar light curve presents two peaks offset from the radio peak by phases 0.96 $\pm$ 0.01 and 0.33 $\pm$ 0.02. New constraining upper limits on the pulsar emission are derived below 1 GeV and confirm a severe spectral break at a few tens of MeV. The nebular spectrum in the 1 - 100 GeV energy range is well described by a power-law with a spectral index of (1.57 $\pm$ 0.17 $\pm$ 0.13) and a flux above 1 GeV of (2.91 $\pm$ 0.79 $\pm$ 1.35) 10^{-9} cm^{-2} s^{-1}. The first errors represent the statistical errors on the fit parameters, while the second ones are the systematic uncertainties. The LAT spectrum of the nebula connects nicely with Cherenkov observations, and indicates a spectral break between GeV and TeV energies.Comment: 14 pages, 6 figures, accepted for publication by Ap

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Long term records of erosional change from marine ferromanganese crusts

Ferromanganese crusts from the Atlantic, Indian and Pacific Oceans record the Nd and Pb isotope compositions of the water masses from which they form as hydrogenous precipitates. The10Be/9Be-calibrated time series for crusts are compared to estimates based on Co-contents, from which the equatorial Pacific crusts studied are inferred to have recorded ca. 60 Ma of Pacific deep water history. Time series of ɛNd show that the oceans have maintained a strong provinciality in Nd isotopic composition, determined by terrigenous inputs, over periods of up to 60 Ma. Superimposed on the distinct basin-specific signatures are variations in Nd and Pb isotope time series which have been particularly marked over the last 5 Ma. It is shown that changes in erosional inputs, particularly associated with Himalayan uplift and the northern hemisphere glaciation have influenced Indian and Atlantic Ocean deep water isotopic compositions respectively. There is no evidence so far for an imprint of the final closure of the Panama Isthmus on the Pb and Nd isotopic composition in either Atlantic or Pacific deep water masses

A Population of Gamma-Ray Millisecond Pulsars Seen with the Fermi Large Area Telescope

Gamma-Ray Pulsar Bonanza Most of the pulsars we know about were detected through their radio emission; a few are known to pulse gamma rays but were first detected at other wavelengths (see the Perspective by Halpern ). Using the Fermi Gamma-Ray Space Telescope, Abdo et al. (p. 840 , published online 2 July; see the cover) report the detection of 16 previously unknown pulsars based on their gamma-ray emission alone. Thirteen of these coincide with previously unidentified gamma-ray sources, solving the 30-year-old mystery of their identities. Pulsars are fast-rotating neutron stars. With time they slow down and cease to radiate; however, if they are in a binary system, they can have their spin rates increased by mass transfer from their companion stars, starting a new life as millisecond pulsars. In another study, Abdo et al. (p. 845 ) report the detection of gamma-ray emission from the globular cluster 47 Tucanae, which is coming from an ensemble of millisecond pulsars in the cluster's core. The data imply that there are up to 60 millisecond pulsars in 47 Tucanae, twice as many as predicted by radio observations. In a further companion study, Abdo et al. (p. 848 , published online 2 July) searched Fermi Large Area Telescope data for pulsations from all known millisecond pulsars outside of stellar clusters, finding gamma-ray pulsations for eight of them. Their properties resemble those of other gamma-ray pulsars, suggesting that they share the same basic emission mechanism. Indeed, both sets of pulsars favor emission models in which the gamma rays are produced in the outer magnetosphere of the neutron star

Fermi Detection of a Luminous Gamma-ray Pulsar in a Globular Cluster

We report the Fermi Large Area Telescope detection of gamma-ray (>100 megaelectronvolts) pulsations from pulsar J1823-3021A in the globular cluster NGC 6624 with high significance (~7 sigma). Its gamma-ray luminosity L_gamma = (8.4 +/- 1.6) x10^34 ergs per second, is the highest observed for any millisecond pulsar (MSP) to date, and it accounts for most of the cluster emission. The non-detection of the cluster in the off-pulse phase implies that its contains < 32 gamma-ray MSPs, not ~100 as previously estimated. The gamma-ray luminosity indicates that the unusually large rate of change of its period is caused by its intrinsic spin-down. This implies that J1823-3021A, has the largest magnetic field and is the youngest MSP ever detected, and that such anomalous objects might be forming at rates comparable to those of the more normal MSPs.Comment: Accepted for publication in Scienc