Effects of xanthine amine congener on hypoxic coronary resistance and venous and epicardial adenosine concentrations

Objective: The aim was to define the contributions of interstitial and vascular adenosine in regulating coronary vascular resistance during hypoxia. To help in the assessment of adenosine in the vasodilator response, a potent adenosine receptor antagonist, xanthine amine congener (XAC), was used to block adenosine receptors. Methods: Seven isolated guinea pig hearts were perfused at constant flow with Krebs buffer. Coronary vascular resistance was determined during normoxia (95% O2) and mild hypoxia (60% O2) in the absence or presence of 200 or 400 nM XAC. Interstitial fluid was sampled by the epicardial disc technique and the interstitial concentration of XAC (ISF[XAC]) was determined directly by a radioreceptor assay or as tritiated XAC. Venous and epicardial concentrations of adenosine were determined by high performance liquid chromatography. In six additional experiments, the vasodilator effect of 1 μM intracoronary adenosine was measured in the absence or presence of 100 or 200 nM XAC. Results: Mild hypoxia decreased coronary resistance by 37(SEM 4)% in the absence of XAC and 26(5)% or 17(4)% in the presence of 200 or 400 nM XAC, respectively. ISF[XAC] rapidly equilibrated with [XAC] in the arterial perfusate or venous effluent. XAC 400 nM markedly increased (p<0.05) the hypoxic levels of venous and epicardial fluid adenosine from 49(19) and 251(42) nM to 75(11) and 495(48) nM, respectively. XAC 100-200 nM almost completely prevented the vasodilatation induced by 1 μM intracoronary adenosine. Conclusions: Adenosine mediates at least 54% of hypoxic vasodilatation. XAC rapidly equilibrates within the myocardial interstitial space and, as a result of blocking adenosine receptors, increases interstitial and venous adenosine concentrations. Increases in interstitial adenosine may partially overcome the adenosine receptor blockade by XAC, thereby reducing the effectiveness of XAC in attenuating the hypoxic vasodilatation. XAC attenuates intracoronary adenosine induced vasodilatation (mediated by endothelial adenosine receptors) much more effectively than it attenuates hypoxic vasodilatation, underscoring the minimal role played by the endothelial receptors in hypoxic vasodilatation. Cardiovascular Research 1994;28:604-60

Statistical Properties of the Interbeat Interval Cascade in Human Subjects

Statistical properties of interbeat intervals cascade are evaluated by considering the joint probability distribution $P(\Delta x_2,\tau_2;\Delta x_1,\tau_1)$ for two interbeat increments $\Delta x_1$ and $\Delta x_2$ of different time scales $\tau_1$ and $\tau_2$. We present evidence that the conditional probability distribution $P(\Delta x_2,\tau_2|\Delta x_1,\tau_1)$ may obey a Chapman-Kolmogorov equation. The corresponding Kramers-Moyal (KM) coefficients are evaluated. It is shown that while the first and second KM coefficients, i.e., the drift and diffusion coefficients, take on well-defined and significant values, the higher-order coefficients in the KM expansion are very small. As a result, the joint probability distributions of the increments in the interbeat intervals obey a Fokker-Planck equation. The method provides a novel technique for distinguishing the two classes of subjects in terms of the drift and diffusion coefficients, which behave differently for two classes of the subjects, namely, healthy subjects and those with congestive heart failure.Comment: 5 pages, 6 figure

Stochastic Feedback and the Regulation of Biological Rhythms

We propose a general approach to the question of how biological rhythms spontaneously self-regulate, based on the concept of ``stochastic feedback''. We illustrate this approach by considering the neuroautonomic regulation of the heart rate. The model generates complex dynamics and successfully accounts for key characteristics of cardiac variability, including the $1/f$ power spectrum, the functional form and scaling of the distribution of variations, and correlations in the Fourier phases. Our results suggest that in healthy systems the control mechanisms operate to drive the system away from extreme values while not allowing it to settle down to a constant output.Comment: 15 pages, latex2e using rotate and epsf, with 4 ps figures. Submitted to PR

Quantum free energy differences from non-equilibrium path integrals: I. Methods and numerical application

The imaginary-time path integral representation of the canonical partition function of a quantum system and non-equilibrium work fluctuation relations are combined to yield methods for computing free energy differences in quantum systems using non-equilibrium processes. The path integral representation is isomorphic to the configurational partition function of a classical field theory, to which a natural but fictitious Hamiltonian dynamics is associated. It is shown that if this system is prepared in an equilibrium state, after which a control parameter in the fictitious Hamiltonian is changed in a finite time, then formally the Jarzynski non-equilibrium work relation and the Crooks fluctuation relation are shown to hold, where work is defined as the change in the energy as given by the fictitious Hamiltonian. Since the energy diverges for the classical field theory in canonical equilibrium, two regularization methods are introduced which limit the number of degrees of freedom to be finite. The numerical applicability of the methods is demonstrated for a quartic double-well potential with varying asymmetry. A general parameter-free smoothing procedure for the work distribution functions is useful in this context.Comment: 20 pages, 4 figures. Added clarifying remarks and fixed typo

Displacement field and elastic constants in non-ideal crystals

In this work a periodic crystal with point defects is described in the framework of linear response theory for broken symmetry states using correlation functions and Zwanzig-Mori equations. The main results are microscopic expressions for the elastic constants and for the coarse-grained density, point-defect density, and displacement field, which are valid in real crystals, where vacancies and interstitials are present. The coarse-grained density field differs from the small wave vector limit of the microscopic density. In the long wavelength limit, we recover the phenomenological description of elasticity theory including the defect density.Comment: Phys Rev. B, in print (2010

Polycyclic aromatic hydrocarbons with SPICA

Thanks to high sensitivity and angular resolution and broad spectral coverage, SPICA will offer a unique opportunity to better characterize the nature of polycyclic aromatic hydrocarbons (PAHs) and very small grains (VSGs), to better use them as probes of astrophysical environments. The angular resolution will enable to probe the chemical frontiers in the evolution process from VSGs to neutral PAHs, to ionized PAHs and to "Grand-PAHs" in photodissotiation regions and HII regions, as a function of G$_0$/n (UV radiation field / density). High sensitivity will favor the detection of the far-IR skeletal emission bands of PAHs, which provide specific fingerprints and could lead to the identification of individual PAHs. This overall characterization will allow to use PAH and VSG populations as tracers of physical conditions in spatially resolved protoplanetary disks and nearby galaxies (using mid-IR instruments), and in high redshift galaxies (using the far-IR instrument), thanks to the broad spectral coverage SPICA provides. Based on our previous experience with ISO and Spitzer we discuss how these goals can be reached.Comment: To appear in Proc. Workshop "The Space Infrared Telescope for Cosmology & Astrophysics: Revealing the Origins of Planets and Galaxies". Eds. A.M. Heras, B. Swinyard, K. Isaak, and J.R. Goicoeche

Influence of primary particle density in the morphology of agglomerates

Agglomeration processes occur in many different realms of science such as colloid and aerosol formation or formation of bacterial colonies. We study the influence of primary particle density in agglomerate structure using diffusion-controlled Monte Carlo simulations with realistic space scales through different regimes (DLA and DLCA). The equivalence of Monte Carlo time steps to real time scales is given by Hirsch's hydrodynamical theory of Brownian motion. Agglomerate behavior at different time stages of the simulations suggests that three indices (fractal exponent, coordination number and eccentricity index) characterize agglomerate geometry. Using these indices, we have found that the initial density of primary particles greatly influences the final structure of the agglomerate as observed in recent experimental works.Comment: 11 pages, 13 figures, PRE, to appea

Fluids of hard ellipsoids: Phase diagram including a nematic instability from Percus-Yevick theory

An important aspect of molecular fluids is the relation between orientation and translation parts of the two-particle correlations. Especially the detailed knowledge of the influence of orientation correlations is needed to explain and calculate in detail the occurrence of a nematic phase. The simplest model system which shows both orientation and translation correlations is a system of hard ellipsoids. We investigate an isotropic fluid formed of hard ellipsoids with Percus-Yevick theory. Solving the Percus-Yevick equations self-consistently in the high density regime gives a clear criterion for a nematic instability. We calculate in detail the equilibrium phase diagram for a fluid of hard ellipsoids of revolution. Our results compare well with Monte Carlo Simulations and density functional theory.Comment: 7 pages including 4 figure

Rotational Correlation Functions of Single Molecules

Single molecule rotational correlation functions are analyzed for several reorientation geometries. Even for the simplest model of isotropic rotational diffusion our findings predict non-exponential correlation functions to be observed by polarization sensitive single molecule fluorescence microscopy. This may have a deep impact on interpreting the results of molecular reorientation measurements in heterogeneous environments.Comment: 5 pages, 4 figure