Impact Of Alpha Research Articles

Impact of alpha- and beta-adrenergic receptor blockers on fractional flow reserve and index of microvascular resistance.

We investigated the effect of β- and α-adrenergic blockers on fractional flow reserve (FFR) and index of microvascular resistance (IMR). In 43 patients (pts) with intermediate stenoses, we measured FFR and IMR before and after nonselective β-blocker propranolol (30 μg/kg, n = 20) and selective β1-blocker metoprolol (40 μg/kg, n = 23) IC; (b) In additional 21 pts after percutaneous coronary intervention (PCI), FFR and IMR were measured before and after α-blocker phentolamine (3 mg) IC. Neither propranolol nor metoprolol changed values of FFR and IMR. Phentolamine slightly decreased FFR (from 0.88 ± 0.05 to 0.87 ± 0.06, p = 0.025) but did not change IMR. FFR decreased from >0.80 to ≤0.80 in 3 pts (14%), but in none, the value decreased to <0.75. β-blockers do not affect FFR and IMR in intermediate stenoses. After PCI, a mild decrease in FFR occurs after α-blockers, though of limited clinical impact.

Pivotal Role of the α2A-Adrenoceptor in Producing Inflammation and Organ Injury in a Rat Model of Sepsis

BackgroundNorepinephrine (NE) modulates the responsiveness of macrophages to proinflammatory stimuli through the activation of adrenergic receptors (ARs). Being part of the stress response, early increases of NE in sepsis sustain adverse systemic inflammatory responses. The intestine is an important source of NE release in the early stage of cecal ligation and puncture (CLP)-induced sepsis in rats, which then stimulates TNF-α production in Kupffer cells (KCs) through the activation of the α2-AR. It is important to know which of the three α2-AR subtypes (i.e., α2A, α2B or α2C) is responsible for the upregulation of TNF-α production. The aim of this study was to determine the contribution of α2A-AR in this process.Methodology/Principal FindingsAdult male rats underwent CLP and KCs were isolated 2 h later. Gene expression of α2A-AR was determined. In additional experiments, cultured KCs were incubated with NE with or without BRL-44408 maleate, a specific α2A-AR antagonist, and intraportal infusion of NE for 2 h with or without BRL-44408 maleate was carried out in normal animals. Finally, the impact of α2A-AR activation by NE was investigated under inflammatory conditions (i.e., endotoxemia and CLP). Gene expression of the α2A-AR subtype was significantly upregulated after CLP. NE increased the release of TNF-α in cultured KCs, which was specifically inhibited by the α2A-AR antagonist BRL-44408. Equally, intraportal NE infusion increased TNF-α gene expression in KCs and plasma TNF-α which was also abrogated by co-administration of BRL-44408. NE also potentiated LPS-induced TNF-α release via the α2A-AR in vitro and in vivo. This potentiation of TNF-α release by NE was mediated through the α2A-AR coupled Gαi protein and the activation of the p38 MAP kinase. Treatment of septic animals with BRL-44408 suppressed TNF-α, prevented multiple organ injury and significantly improved survival from 45% to 75%.Conclusions/SignificanceOur novel finding is that hyperresponsiveness to α2-AR stimulation observed in sepsis is primarily due to an increase in α2A-AR expression in KCs. This appears to be in part responsible for the increased proinflammatory response and ensuing organ injury in sepsis. These findings provide important feasibility information for further developing the α2A-AR antagonist as a new therapy for sepsis.

Low-velocity effects in L-subshell ionisation of Ta and W induced by proton, deuteron and alpha impact

L-subshell X-ray production cross sections were measured for Ta and W bombarded by 0.20 to 0.90 MeV u-1 protons and deuterons and by 0.2 to 0.45 MeV u-1 alpha particles. Lalpha Lgamma 1 and Lgamma 2,3 lines were selected to convert X-ray production cross sections into ionisation cross sections. The deuteron to proton-induced cross section ratios show that the Coulomb and energy loss effects are well accounted for in all subshells. The alpha to deuteron-induced cross section ratios show that the theory overcorrects the binding effect, the theoretical ratios being lower than the experimental ones by roughly 25% for the L3 subshell and 75% for the L2 subshell. It is argued that this difference between the ratios, and the poor agreement on the L2-subshell absolute cross sections, may be accounted for by assuming a 10-20% deviation in the values used for the fluorescence and Coster-Kronig yields and for the emission rates; such a deviation may be induced by the projectile.

L-shell X-ray production cross sections for Au, Pb and U by proton, deuteron and alpha impact

Experimental proton-, deuteron- and alpha-induced Lalpha , Lbeta , Lgamma and Ll X-ray production absolute cross section values for the elements Au, Pb and U in the incident energy range 0.2-0.45 MeV u-1 for alphas and 0.2-0.9 MeV u-1 for protons and deuterons are presented. Accurate values for ratios of production cross sections of the same L line by different projectiles and for intensity ratios of different L lines excited by the same projectile are obtained from the present results, experimental conditions being kept constant for the various measurements. The experimental results are compared with theory using the procedure recommended by Brandt and Lapicki (1979, 1981) to obtain theoretical values for the ionisation cross sections allowing for relativistic, binding, Coulomb and energy loss effects. The absolute experimental and theoretical cross section values show degrees of agreement which are different for the various L lines and also depend on the projectile and its velocity. From the values of the cross section ratios for production of the same L line by different projectiles it is argued that the proposed correction for the binding effect is too large and that for the Coulomb and energy loss effects still needs to be improved at the lowest velocities. The intensity ratios of different L lines produced by the same projectile seem to show that the usually accepted values of fluorescence and Coster-Kronig yields are unable to produce agreement with experiment.

On the mechanism of scintillation of helium, helium-argon and helium-neon mixtures induced by alpha impact

The scintillation of helium is explained by de-excitation of the excited molecule formed by a three body collision of a metastable atom with ground state atoms.

Optical spectra excited in high pressure noble gases by alpha impact

The atomic spectra observed in the pure noble gases are interpreted through the dominant processes of direct excitation by alpha and electron impact, trapping of vacuum ultraviolet resonance radiation, and excitation transfer effects resulting from two-body collisions with ground state atoms. The pressure dependence of helium line intensities may be explained with effective depletion cross sections that are in the order of 10 −15 cm 2. The absolute intensities emitted from helium are in approximate agreement with cross sections calculated from the Born approximation if allowance is made for these collision effects. The results indicate that the light emitted from atomic transitions in all of the noble gases in the range between 2400 and 5500 A represents a negligible fraction of the total excitation. No evidence was found for a recombination spectrum in any of the gases. The weak lines observed in pure helium and neon were identified as atomic transitions which are normally present in the discharge spectrum at low pressures. Two weak, unidentified lines of equal intensity were found in pure argon at 3083 ± 3 A and 3094 ± 3 A. In pure krypton and xenon, broad diatomic molecular bands were found to dominate the spectrum. The integrated photon counting rates for pure xenon, krypton, argon, neon, and helium were in the ratio 240:90:3:3:1 at 350 mm Hg. Nitrogen impurity bands dominated the spectra in most helium, neon, and argon samples used, and the sensitivity to nitrogen was in that order. First negative bands of N 2 + were encountered in helium and neon, and the second positive bands of N 2 were found in argon. It was concluded that the following nitrogen excitation mechanisms were dominant: charge exchange with the molecular ion, He 2 +, in the case of helium; collision with a high excited state, probably the 4 3 P 2 or 4 3 P 1, in the case of neon; collision with the 3 P 2 metastable level in the case of argon. The 0,0 N 2 + band dominated the helium spectrum for less than one part N 2 in 10 8 at 350 mm Hg. The results in NeN 2 mixtures place an upper limit on the available energy from thermalized Ne 2 + ions of 18.75 ev. The relative C 3 π u populations observed in the AN 2 mixtures were approximately those which would be expected if the Franck-Condon principle were obeyed in the collision excitation from the nitrogen ground state. Only the second positive bands were observed in high pressure reagent grade nitrogen and the intensities were weaker than those found in the AN 2 mixtures. Comparisons are given between calculated and measured relative transition probabilities for most of the nitrogen bands observed. The relation between this work, average energy per ion pair measurements, and gas scintillation counters is discussed.

Optical spectra excited in high pressure noble gases by alpha impact: W. R. Bennett, Jr. Columbia University, New York, New York, and Yale University, New Haven, Connecticut

Optical spectra excited in high pressure noble gases by alpha impact: W. R. Bennett, Jr. Columbia University, New York, New York, and Yale University, New Haven, Connecticut