Coronary sinus ostial occlusion during retrograde delivery of cardioplegic solution significantly improves cardioplegic distribution and efficacy

AbstractThis study documents the gross flow characteristics and capillary distribution of cardioplegic solution delivered retrogradely with the coronary sinus open versus closed. Methods : Five explanted human hearts from transplant recipients were used as experimental models. Hearts served as their own controls and received two doses of warm blood cardioplegic solution, each containing colored microspheres. The first dose was delivered through a retroperfusion catheter with the coronary sinus open and the second dose was delivered with the sinus occluded. Capillary flow was measured at twelve ventricular sites and gross flow was measured by examining coronary sinus regurgitation, thebesian vein drainage, and aortic effluent (nutrient flow). Results : Coronary sinus ostial occlusion allowed for a significant decrease in total cardioplegic flow (1.74 ± 0.40 ml/gm versus 1.06 ± 0.32 ml/gm; p < 0.05) to occur while maintaining an identical intracoronary sinus pressure. Ostial occlusion also resulted in an increase in the ratio of nutrient flow/total cardioplegic flow from 32.3% ± 15.1% to 61.3% ± 7.9% (p < 0.05). A statistically significant improvement in capillary flow was found at the midventricular level in the posterior intraventricular septum and posterolateral right ventricular free wall. This improvement was also documented for the intraventricular septum and right ventricle at the level of the apex. Conclusion : Coronary sinus occlusion during retrograde cardioplegia significantly improves cardioplegic delivery to the right ventricle and posterior intraventricular septum. Furthermore, the technique affords a significant improvement in nutrient cardioplegic flow while reducing the overall volume of cardioplegic solution administered. ( J T HORAC C ARDIOVASC S URG 1995; 109: 941-7

Protein Dynamics in Individual Human Cells: Experiment and Theory

A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle–dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell–cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell–cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells

Protein Dynamics in Individual Human Cells: Experiment and Theory

A current challenge in biology is to understand the dynamics of protein circuits in living human cells. Can one define and test equations for the dynamics and variability of a protein over time? Here, we address this experimentally and theoretically, by means of accurate time-resolved measurements of endogenously tagged proteins in individual human cells. As a model system, we choose three stable proteins displaying cell-cycle–dependant dynamics. We find that protein accumulation with time per cell is quadratic for proteins with long mRNA life times and approximately linear for a protein with short mRNA lifetime. Both behaviors correspond to a classical model of transcription and translation. A stochastic model, in which genes slowly switch between ON and OFF states, captures measured cell–cell variability. The data suggests, in accordance with the model, that switching to the gene ON state is exponentially distributed and that the cell–cell distribution of protein levels can be approximated by a Gamma distribution throughout the cell cycle. These results suggest that relatively simple models may describe protein dynamics in individual human cells

Blockade of the extracellular signal-regulated kinase pathway by U0126 attenuates neuronal damage following circulatory arrest

AbstractObjectivesThe extracellular signal-regulated kinase pathway of the mitogen-activated protein kinase signal transduction cascade has been implicated in the neuronal and endothelial dysfunction witnessed following cerebral ischemia-reperfusion injury. Extracellular signal-regulated kinase is activated by mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2. We evaluated the ability of a mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2–specific inhibitor (U0126) to block extracellular signal-regulated kinase activation and mitigate ischemic neuronal damage in a model of deep hypothermic circulatory arrest.MethodsPiglets underwent normal flow cardiopulmonary bypass (control, n = 4), deep hypothermic circulatory arrest (n = 6), and deep hypothermic circulatory arrest with U0126 (n = 5) at 20°C for 60 minutes. The deep hypothermic circulatory arrest with U0126 group was given 200 μg/kg of U0126 45 minutes prior to initiation of bypass followed by 100 μg/kg at reperfusion. Following 24 hours of post–cardiopulmonary bypass recovery, brains were harvested. Eleven distinct cortical regions were evaluated for neuronal damage using hematoxylin and eosin staining. A section of ischemic cortex was further evaluated by immunohistochemistry with rabbit polyclonal antibody against phosphorylated extracellular signal-regulated kinase 1/2.ResultsThe deep hypothermic circulatory arrest and deep hypothermic circulatory arrest with U0126 groups displayed diffuse ischemic changes. However, the deep hypothermic circulatory arrest with U0126 group possessed significantly lower neuronal damage scores in the right frontal watershed zone of cerebral cortex, basal ganglia, and thalamus (P ≤ .05) and an overall trend toward neuroprotection versus the deep hypothermic circulatory arrest group. This neuroprotection was accompanied by nearly complete blockade of phosphorylated extracellular signal-regulated kinase in the cerebral vascular endothelium.ConclusionsIn this experimental model of deep hypothermic circulatory arrest, U0126 blocked extracellular signal-regulated kinase activation and provided a significant neuroprotective effect. These results support targeting of the extracellular signal-regulated kinase pathway for inhibition as a novel therapeutic approach to mitigate neuronal damage following deep hypothermic circulatory arrest

Battery-ultracapacitor hybrids for pulsed current loads: A review

Battery versus hybrid power sources performance is examined in the manuscript. Passive, semi-active and fully active battery-ultracapacitor hybrids show obvious superiority over battery only powered pulsed current loads. Passive hybrid is the most simple and cheap arrangement, however its uncontrolled nature results in several drawbacks during the operation. On the other hand, the fully active hybrids achieve superior performance at the expense of two DC-DC converters and the corresponding control circuitry. The trade off between the topologies is the semi-active hybrid, employing only one DC-DC converter and attaining a compromising performance. The thorough characterization of each topology and sub-topology is presented in the manuscript and design methodology is derived for a particular case of pulsed current load.Hybrid sources Power electronics Battery Ultracapacitor

The relative advantages of criminal versus administrative environmental enforcement actions in Israel

Most environmental enforcement programs have separate criminal and administrative procedures for addressing violations. Pitting "criminal" versus "administrative" enforcement as mutually exclusive alternatives constitutes a "false dilemma". Clearly, the government response should be influenced by the severity of pollution and the specific circumstances of the polluter. Yet, policy makers seeking to improve environmental compliance need to have a clearer picture about the merits of each approach and their relative effectiveness. This research empirically assesses the effectiveness of criminal versus administrative enforcement activities in Israel. After considering the philosophical implications associated with each regulatory approach, the results of a year-long study are presented. A series of performance indicators are utilized, with particular weight on compliance status in the field, to assess the condition of environmental violations several years subsequent to completion of enforcement activities. The state of 100 violations of air, water and hazardous materials laws that had been addressed through the criminal process were matched with results of comparable violations, against which administrative actions were taken. Results suggest that while criminal enforcement is a longer process, compliance following these actions was significantly greater than in administrative enforcement cases. The findings also underline the significance of a systematic follow-up system for tracking violations after enforcement actions are complete. Finally, the study confirms the benefits of targeted assistance to improve compliance among violators of environmental standards

The <i>C</i>. <i>elegans</i> Connectome Consists of Homogenous Circuits with Defined Functional Roles

<div><p>A major goal of systems neuroscience is to decipher the structure-function relationship in neural networks. Here we study network functionality in light of the common-neighbor-rule (CNR) in which a pair of neurons is more likely to be connected the more common neighbors it shares. Focusing on the fully-mapped neural network of <i>C</i>. <i>elegans</i> worms, we establish that the CNR is an emerging property in this connectome. Moreover, sets of common neighbors form homogenous structures that appear in defined layers of the network. Simulations of signal propagation reveal their potential functional roles: signal amplification and short-term memory at the sensory/inter-neuron layer, and synchronized activity at the motoneuron layer supporting coordinated movement. A coarse-grained view of the neural network based on homogenous connected sets alone reveals a simple modular network architecture that is intuitive to understand. These findings provide a novel framework for analyzing larger, more complex, connectomes once these become available.</p></div

Topological Overview of Auxiliary Source Circuits for Grid-Tied Converters

This paper reviews different types of capacitors and auxiliary source circuit topologies and presents an introduction to control strategies used for circuit applications reducing DC-BUS capacitance. The paper argues in favor of replacing bulky electrolytic capacitors in capacitor-supported power electronic systems with auxiliary source circuits. DC-BUS capacitors are widely used in grid-tied power converters (rectifiers) and utilized for power balance, voltage ripple limitation, and short-term energy storage. The electrolyte capacitor is the Achilles heel of any rectifier and power converter due to its higher rate of failure than other circuitry components. Auxiliary source circuits are key components to qualitatively improve the reliability of the DC links, where they divert the instantaneous pulsating power into extra reliable storage components. Unlike previous work, this review serves to provide a clear picture of an auxiliary source circuit design, in favor of optimal solution selection according to the specific application. Therefore, energy storage components (capacitors), topologies, and control strategies of auxiliary source circuits are comprehensively reviewed in this paper. Additionally, detailed explanations, comparisons, and discussions of auxiliary source circuits are offered