Oxygen Transport during Ex Situ Machine Perfusion of Donor Livers Using Red Blood Cells or Artificial Oxygen Carriers

Oxygenated ex situ machine perfusion of donor livers is an alternative for static cold preservation that can be performed at temperatures from 0 °C to 37 °C. Organ metabolism depends on oxygen to produce adenosine triphosphate and temperatures below 37 °C reduce the metabolic rate and oxygen requirements. The transport and delivery of oxygen in machine perfusion are key determinants in preserving organ viability and cellular function. Oxygen delivery is more challenging than carbon dioxide removal, and oxygenation of the perfusion fluid is temperature dependent. The maximal oxygen content of water-based solutions is inversely related to the temperature, while cellular oxygen demand correlates positively with temperature. Machine perfusion above 20 °C will therefore require an oxygen carrier to enable sufficient oxygen delivery to the liver. Human red blood cells are the most physiological oxygen carriers. Alternative artificial oxygen transporters are hemoglobin-based oxygen carriers, perfluorocarbons, and an extracellular oxygen carrier derived from a marine invertebrate. We describe the principles of oxygen transport, delivery, and consumption in machine perfusion for donor livers using different oxygen carrier-based perfusion solutions and we discuss the properties, advantages, and disadvantages of these carriers and their use.     

D1/D5 dopamine receptors inhibit depotentiation at CA1 synapses via cAMP-dependent mechanism

Recent work has shown that D1/D5 dopamine receptors can enhance long-term potentiation (LTP). We investigated whether D1/D5 receptors also affect depotentiation, the reversal of LTP by low-frequency stimulation. D1/D5 agonists greatly reduced depotentiation, an effect that was inhibited by a D1/D5 antagonist. The D1/D5 effect appears to be mediated by adenylyl cyclase (AC) and cAMP-dependent protein kinase (PKA), because it was mimicked by the AC activator forskolin and was inhibited by the AC and PKA inhibitors. In vivo studies show that dopamine is released when a reward occurs. Our results raise the possibility that the memory of events before reward might be retained selectively, because dopamine blocks their erasure.     

Prior exposure to alcohol and the stress-response-dampening effect.

This study investigated the effect of receiving prior exposure to alcohol and the laboratory environment on the stress-reducing effects of alcohol. Sixteen heavy drinkers were matched on a measure of risk for alcoholism and assigned to 1 of 2 groups. During Days 1 and 2, the alcohol group drank alcohol (0.5 g/kg) and the placebo group drank a placebo in a distinct laboratory environment while measures of heart rate were obtained. During Day 3, both groups received a placebo in an effort to discern whether the groups differed in their response to alcohol cues. During Day 4, both groups received alcohol followed by a stressful task. The groups differed in neither their response to alcohol cues nor their initial response to alcohol. However, the alcohol group did demonstrate a reduced heart rate response during the stress phase. These results suggest that the stress-reducing effects of alcohol may reflect the influence of experiential as well as pharmacological factors related to alcohol consumption. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol and social anxiety in males: Behavioral, cognitive, and physiological effects.

To test the tension reduction hypothesis (TRH) of alcohol consumption, 2 studies were conducted to determine the effects of alcohol on heterosexual social anxiety. In Study 1 a clinical population of 32 socially anxious males drank 0 or .5 ml/kg of pure ethanol and then interacted with a female confederate. Expectancies about alcohol consumption and its effects were manipulated by using both a placebo beverage and instructional sets about the positive or negative effects of alcohol. Physiological, cognitive/self-report, and behavioral measures (e.g., Fear Thermometer and the Multiple Affect Adjective Check List) indicated that alcohol produced a marked impairment in the shy Ss while not appreciably affecting physiological responses. Study 2 employed 36 undergraduate males and 3 dosages of alcohol (0, .33, and .75 ml/kg). Once again alcohol impaired both behavioral performance and self-report ratings. In addition, the high-dosage alcohol group experienced greater sustained cardiac acceleration as a function of the social interaction than did the other 2 groups, suggesting the possibility of an alcohol–stress relationship. Data disconfirm the utility of a global TRH in explaining the psychological and physiological effects of alcohol ingestion. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An oscillatory short-term memory buffer model can account for data on the Sternberg task

A limited number (7 +/- 2) of items can be held in human short-term memory (STM). We have previously suggested that observed dual (theta and gamma) oscillations could underlie a multiplexing mechanism that enables a single network to actively store up to seven memories. Here we have asked whether models of this kind can account for the data on the Sternberg task, the most quantitative measurements of memory search available. We have found several variants of the oscillatory search model that account for the quantitative dependence of the reaction time distribution on the number of items (S) held in STM. The models differ on the issues of (1) whether theta frequency varies with S and (2) whether the phase of ongoing oscillations is reset by the probe. Using these models the frequencies of dual oscillations can be derived from psychophysical data. The derived values (ftheta = 6-10 Hz; fgamma = 45-60 Hz) are in reasonable agreement with experimental values. The exhaustive nature of the serial search that has been inferred from psychophysical measurements can be plausibly explained by these oscillatory models. One argument against exhaustive serial search has been the existence of serial position effects. We find that these effects can be explained by short-term repetition priming in the context of serial scanning models. Our results strengthen the case for serial processing and point to experiments that discriminate between variants of the serial scanning process.