Evaluation of adenosine, lidocaine, and magnesium for enhancement of platelet function during storage

Background: The combination of adenosine, lidocaine, and magnesium (Mg2+) (ALM) has demonstrated cardioprotective and resuscitative properties in models of cardiac arrest and hemorrhagic shock that are linked to reduction of metabolic demand. Platelets play a key role in resuscitation strategies for ATC but suffer from loss of function following storage in part owing to mitochondrial exhaustion. This study evaluates whether ALM also demonstrates protective properties in stored platelet preparations. Methods: Platelets were tested at (baseline, Day 5, Day 10, and Day 15) at 22 degrees C (room temperature) or 4 degrees C in 100% plasma and platelet additive solution. Adenosine, lidocaine, and magnesium treatment or its individual components (A, L, M, or combinations) were added directly to the minibags at baseline for storage. Measurements consisted of blood gas and chemistry analyses, thromboelastography, impedance aggregometry, and flow cytometry. Results: Blood gas and cell analysis, as well as flow cytometry measures, demonstrated only differences between temperature groups starting at Day 5 (p < 0.05) and no differences between treatment groups. Aggregation response to collagen (A only, M only, and ALM high dose) and thrombin receptor activation peptide (A + M, and ALM high dose) was significantly greater at Day 5 compared to respective 4 degrees C (100% plasma) controls (p < 0.05). Thromboelastography analysis revealed significant preservation of all measures (reaction time, maximum amplitude, and angle) at Day 15 for 4 degrees C-stored samples in 100% plasma in both controls (no ALM) and ALM treatment compared to room temperature (p < 0.05); no differences were observed between the ALM and control groups. Conclusions: The mechanism of ALM's protective effect remains unclear; key cellular functions may be required to provide protection. In this study, improvements in collagen and thrombin receptor activation peptide aggregation were seen when compared to 4 degrees C-stored plasma samples although no improvements were seen when compared to 4 degrees C-stored platelet additive solution platelets

Distinct causal influences of parietal versus frontal areas on human visual cortex: evidence from concurrent TMS-fMRI

It has often been proposed that regions of the human parietal and/or frontal lobe may modulate activity in visual cortex, for example, during selective attention or saccade preparation. However, direct evidence for such causal claims is largely missing in human studies, and it remains unclear to what degree the putative roles of parietal and frontal regions in modulating visual cortex may differ. Here we used transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) concurrently, to show that stimulating right human intraparietal sulcus (IPS, at a site previously implicated in attention) elicits a pattern of activity changes in visual cortex that strongly depends on current visual context. Increased intensity of IPS TMS affected the blood oxygen level-dependent (BOLD) signal in V5/MT+ only when moving stimuli were present to drive this visual region, whereas TMS-elicited BOLD signal changes were observed in areas V1-V4 only during the absence of visual input. These influences of IPS TMS upon remote visual cortex differed significantly from corresponding effects of frontal (eye field) TMS, in terms of how they related to current visual input and their spatial topography for retinotopic areas V1-V4. Our results show directly that parietal and frontal regions can indeed have distinct patterns of causal influence upon functional activity in human visual cortex