Stabilization of the Cardiac Nervous System During Cardiac Stress Induces Cardioprotection

The cardiac nervous system consists of nested reflex feedback loops that interact to regulate regional heart function. Cardiac disease affects multiple components of the cardiac nervous system and the myocytes themselves. This study aims to determine: 1) how select components of the cardiac nervous system respond to acute cardiac stress, including myocardial ischemia (MI) and induced neural imbalance leading to cardiac electrical instability, and 2) how neuromodulation can affect neural-myocyte interactions to induce cardioprotection. Thoracic spinal cord stimulation (SCS) is recognized for its anti-anginal effects and ability to reduce apoptosis in response to acute MI, primarily via modulation of adrenergic efferent systems. The data presented here suggest that cervical SCS exerts similar cardioprotective effects in response to MI, but in contradistinction to thoracic SCS, uses both adrenergic and cholinergic efferent mechanisms to stabilize cardiomyocytes and the arrhythmogenic potential. SCS potentially can use efferent and/or anti-dromically activated cardiac afferents to mediate its cardioprotection. Thoracic SCS mitigates the MI-induced activation of both nodose and dorsal root ganglia cardiac-related afferents, doing so without antidromic activation of the primary cardiac afferents. Instead, thoracic SCS acts through altering the cardiac milieu thereby secondarily affecting the primary afferent sensory transduction. In response to cardiac stressors, reflex activation of efferent activity modifies mechanical and electrical functions of the heart. Excessive activation of neuronal input to the cardiac nervous system can induce arrhythmias. Stimulation of intrathoracic mediastinal nerves directly activates subpopulations of intrinsic cardiac neurons, thereby inducing atrial arrhythmias. Neuromodulation, either thoracic SCS or hexamethonium, suppressed mediastinal nerve stimulation (MSNS)-induced activation of intrinsic cardiac neurons and correspondingly reduced the arrhythmogenic potential. SCS exerted its stabilizing effects on neural processing and subsequent effects on atrial electrical function by selectively targeting local circuit neurons within the intrinsic cardiac nervous system. Together these data indicate that neuromodulation therapy, using SCS, can mitigate the imbalances in cardiac reflex control arising from acute cardiac stress and thereby has the potential to slow the progression of chronic heart disease

Particle Production and Positive Energy Theorems for Charged Black Holes in deSitter

We study quantum mechanical and classical stability properties of Reissner-Nordstrom deSitter spacetimes, which describe black holes with mass $M$ and charge $Q$ in a background with cosmological constant $\Lambda \ge 0$. There are two sources of particle production in these spacetimes; the black hole horizon and the cosmological horizon. A scattering calculation is done to compute the Hawking radiation in these spacetimes. We find that the flux from the black hole horizon equals the flux from the cosmological horizon, if and only if $|Q|=M$, indicating that this is a state of thermodynamic equilibrium. The spectrum, however, is not thermal. We also show that spacetimes containing a number of charge equal to mass black holes with $\Lambda \ge 0$, have supercovariantly constant spinors, suggesting that they may be minimum energy states in a positive energy construction. As a first step in this direction, we present a positive energy construction for asymptotically deSitter spacetimes with vanishing charge. Because the construction depends only on a spatial slice, our result also holds for spacetimes which are asymptotically Robertson-Walker.Comment: 11 pages (1 figure not included), UMHEP-39

Komar Integrals in Higher (and Lower) Derivative Gravity

The Komar integral relation of Einstein gravity is generalized to Lovelock theories of gravity. This includes, in particular, a new boundary integral for the Komar mass in Einstein gravity with a nonzero cosmological constant, which has a finite result for asymptotically AdS black holes, without the need for an infinite background subtraction. Explicit computations of the Komar mass are given for black holes in pure Lovelock gravities of all orders and in general Gauss-Bonnet theories.Comment: 16 pages; v2 - references and comment on relation to Noether charge method adde

Single-charge rotating black holes in four-dimensional gauged supergravity

We consider four-dimensional U(1)^4 gauged supergravity, and obtain asymptotically AdS_4, non-extremal, charged, rotating black holes with one non-zero U(1) charge. The thermodynamic quantities are computed. We obtain a generalization that includes a NUT parameter. The general solution has a discrete symmetry involving inversion of the rotation parameter, and has a string frame metric that admits a rank-2 Killing-Stackel tensor.Comment: 9 page

Attention-deficit/hyperactivity disorder medication and seizures

OBJECTIVE: Individuals with attention-deficit/hyperactivity disorder (ADHD) are at increased risk of seizures, but there is uncertainty about whether ADHD medication treatment increases risk among patients with and without preexisting seizures. METHODS: We followed a sample of 801,838 patients with ADHD who had prescribed drug claims from the Truven Health MarketScan Commercial Claims and Encounters databases to examine whether ADHD medication increases the likelihood of seizures among ADHD patients with and without a history of seizures. First, we assessed overall risk of seizures among patients with ADHD. Second, within-individual concurrent analyses assessed odds of seizure events during months when a patient with ADHD received ADHD medication compared with when the same individual did not, while adjusting for antiepileptic medications. Third, within-individual long-term analyses examined odds of seizure events in relation to the duration of months over the previous 2 years patients received medication. RESULTS: Patients with ADHD were at higher odds for any seizure compared with non-ADHD controls (odds ratio [OR] = 2.33, 95% confidence interval [CI] = 2.24-2.42 males; OR = 2.31, 95% CI = 2.22-2.42 females). In adjusted within-individual comparisons, ADHD medication was associated with lower odds of seizures among patients with (OR = 0.71, 95% CI = 0.60-0.85) and without (OR = 0.71, 95% CI = 0.62-0.82) prior seizures. Long-term within-individual comparisons suggested no evidence of an association between medication use and seizures among individuals with (OR = 0.87, 95% CI = 0.59-1.30) and without (OR = 1.01, 95% CI = 0.80-1.28) a seizure history. CONCLUSIONS: Results reaffirm that patients with ADHD are at higher risk of seizures. However, ADHD medication was associated with lower risk of seizures within individuals while they were dispensed medication, which is not consistent with the hypothesis that ADHD medication increases risk of seizures

Cosmological Multi-Black Hole Solutions

We present simple, analytic solutions to the Einstein-Maxwell equation, which describe an arbitrary number of charged black holes in a spacetime with positive cosmological constant $\Lambda$. In the limit $\Lambda=0$, these solutions reduce to the well known Majumdar-Papapetrou (MP) solutions. Like the MP solutions, each black hole in a $\Lambda >0$ solution has charge $Q$ equal to its mass $M$, up to a possible overall sign. Unlike the $\Lambda = 0$ limit, however, solutions with $\Lambda >0$ are highly dynamical. The black holes move with respect to one another, following natural trajectories in the background deSitter spacetime. Black holes moving apart eventually go out of causal contact. Black holes on approaching trajectories ultimately merge. To our knowledge, these solutions give the first analytic description of coalescing black holes. Likewise, the thermodynamics of the $\Lambda >0$ solutions is quite interesting. Taken individually, a $|Q|=M$ black hole is in thermal equilibrium with the background deSitter Hawking radiation. With more than one black hole, because the solutions are not static, no global equilibrium temperature can be defined. In appropriate limits, however, when the black holes are either close together or far apart, approximate equilibrium states are established.Comment: 15 pages (phyzzx), UMHEP-380 (minor referencing error corrected

Dynamics of the DBI Spike Soliton

We compare oscillations of a fundamental string ending on a D3-brane in two different settings: (1) a test-string radially threading the horizon of an extremal black D3-brane and (2) the spike soliton of the DBI effective action for a D3-brane. Previous work has shown that overall transverse modes of the test-string appear as l=0 modes of the transverse scalar fields of the DBI system. We identify DBI world-volume degrees of freedom that have dynamics matching those of the test-string relative transverse modes. We show that there is a map, resembling T-duality, between relative and overall transverse modes for the test-string that interchanges Neumann and Dirichlet boundary conditions and implies equality of the absorption coefficients for both modes. We give general solutions to the overall and relative transverse parts of the DBI coupled gauge and scalar system and calculate absorption coefficients for the higher angular momentum modes in the low frequency limit. We find that there is a nonzero amplitude for l>0 modes to travel out to infinity along the spike, demonstrating that the spike remains effectively 3+1-dimensional.Comment: 15 pages, 1 figur

Pair Creation of Dilaton Black Holes

We consider dilaton gravity theories in four spacetime dimensions parametrised by a constant $a$, which controls the dilaton coupling, and construct new exact solutions. We first generalise the C-metric of Einstein-Maxwell theory ($a=0$) to solutions corresponding to oppositely charged dilaton black holes undergoing uniform acceleration for general $a$. We next develop a solution generating technique which allows us to ``embed" the dilaton C-metrics in magnetic dilaton Melvin backgrounds, thus generalising the Ernst metric of Einstein-Maxwell theory. By adjusting the parameters appropriately, it is possible to eliminate the nodal singularities of the dilaton C-metrics. For $a<1$ (but not for $a\ge 1$), it is possible to further restrict the parameters so that the dilaton Ernst solutions have a smooth euclidean section with topology $S^2\times S^2-{\rm\{pt\}}$, corresponding to instantons describing the pair production of dilaton black holes in a magnetic field. A different restriction on the parameters leads to smooth instantons for all values of $a$ with topology $S^2\times \R^2$.Comment: 22 pages, EFI-93-51, FERMILAB-Pub-93/272-A, UMHEP-393. (Asymptotics of Ernst solutions clarified, typos repaired