The TOTEM detector at LHC Antchev, G.; Aspell, P.; Atanassov, I. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
05/2010, Letnik:
617, Številka:
1
Journal Article
Recenzirano
The TOTEM experiment, small in size compared to the others at the LHC, is dedicated to the measurement of the total proton–proton cross-sections with a luminosity-independent method and to the study ...of elastic and diffractive scattering at the LHC. To achieve optimum forward coverage for charged particles emitted by the pp collisions in the IP5 interaction point, two tracking telescopes, T1 and T2, will be installed on each side in the pseudo-rapidity region between 3.1 and 6.5, and Roman Pot stations will be placed at distances of 147 and 220
m from IP5. The telescope closest to the interaction point (T1, centred at
z=9
m) consists of Cathode Strip Chambers (CSC), while the second one (T2, centred at 13.5
m), makes use of Gas Electron Multipliers (GEM). The proton detectors in the Roman Pots are silicon devices designed by TOTEM with the specific objective of reducing down to a few tens of microns the insensitive area at the edge. High efficiency as close as possible to the physical detector boundary is an essential feature. It maximizes the experimental acceptance for protons scattered elastically or interactively at polar angles down to a few micro-radians at IP5. To measure protons at the lowest possible emission angles, special beam optics have been conceived to optimize proton detection in terms of acceptance and resolution. The read-out of all TOTEM subsystems is based on the custom-developed digital VFAT chip with trigger capability.
The increase of intracellular Ca
2+
concentration, produced principally by its influx through the L-type Ca
2+
channels, is one of the major contributors to the ischemia-reperfusion injury. The ...inhibition of those channels in different experimental models was effective to ameliorate the post-ischemic damage. However, at a clinical level, the results were contradictory. Recent results of our group obtained in an ¨
ex vivo
¨ heart model demonstrated that a chemical derived from acetazolamide, the N-methylacetazolamide (NMA) protected the heart against ischemia-reperfusion injury, diminishing the infarct size and improving the post-ischemic recovery of myocardial function and mitochondrial dynamic. A significant inhibitory action on L-type Ca
2+
channels was also detected after NMA treatment, suggesting this action as responsible for the beneficial effects on myocardium exerted by this compound. Although these results were promising, the effectiveness of NMA in the treatment of ischemic heart disease in humans as well as the advantages or disadvantages in comparison to the classic calcium antagonists needs to be investigated.
Our objective was to examine the effects of N-methylacetazolamide (NMA), a non‑carbonic anhydrase inhibitor, on ischemia-reperfusion injury. Isolated rat hearts were assigned to the following groups: ...1) Non-ischemic control (NIC):110 min of perfusion and 2) Ischemic control (IC): 30 min of global ischemia and 60 min of reperfusion (R). Both groups were repeated in presence of NMA (5 μM), administered during the first 10 min of R. Infarct size (IS) was measured by TTC staining. Developed pressure (LVDP) and end-diastolic pressure (LVEDP) of the left ventricle were used to assess systolic and diastolic function, respectively. The content of P-Akt, P-PKCε, P-Drp1 and calcineurin Aβ were measured. In cardiomyocytes the L-type Ca2+ current (ICaL) was recorded with the whole-cell configuration of patch-clamp technique. The addition of NMA to non-ischemic hearts decreased 15% the contractility. In ischemic hearts (IC group), NMA decreased IS (22 ± 2% vs 32 ± 2%, p < 0.05) and improved the post-ischemic recovery of myocardial function. At the end of R, LVDP was 54 ± 7% vs 18 ± 3% and LVEDP was 23 ± 8 vs. 55 ± 7 mmHg ¨p < 0.05¨. The level of P-Akt, P-PKCε and P-Drp1 increased and the expression of calcineurin Aβ decreased in NMA treated hearts. Peak ICaL density recorded at 0 mV was smaller in myocytes treated with NMA than in non-treated cells (−1.91 ± 0.15 pA/pF vs −2.32 ± 0.17 pA/pF, p < 0.05). These data suggest that NMA protects the myocardium against ischemia-reperfusion injury through an attenuation of mitochondrial fission by calcineurin/Akt/PKCε-dependent pathways associated to the decrease of ICaL current.
•N-methylacetazolamide (NMA) limits the infarct size and improves the recovery of postischemic myocardial function.•NMA attenuates mitochondrial fission.•-NMA decreases the L-type Ca2+ current (ICaL).•Calcineurin/Akt/PKCε-dependent pathways are involved in the cardioprotection mediated by NMA.
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