The effect of oscillatory flow on the release reaction and aggregation of human platelets

The effect of variable shear rate on the thrombin-induced release of [¹⁴C]serotonin from human platelets was investigated by subjecting washed suspensions containing 5 × 10⁵ cells/μl to laminar oscillatory flow at 37°C in 1-meter lengths of 1.57-mm polyethylene tubing. The suspensions were prepared at 37°C in Tyrodes-albumin containing apyrase to avoid desensitization of the platelets by released ADP. After flow, the sheared sample and a control, incubated at rest at 37°C, were stirred with thrombin at concentrations of 0.04 units/ml (threshold at which aggregation just occurred) and 0.02 units/ml, and the ¹⁴C-activity in the supernatant measured after centrifugation.At time-averaged wall shear rates $\text{G}\text{(R}{}_0\text{) = 2350}\text{sec}{}^{\mathrm{?1}}$ and 20 min shear, there was no significant release of [¹⁴C]serotonin due to flow alone. However, in 53 experimental runs the mean release at 0.02 and 0.04 units/ml exceeded that in the paired controls by 6.1%(±1.4%, SE) and 10.1%(±1.3%) of the total activity in the suspension. The increase in serotonin release was not significant at $\text{G}\text{(R}{}_0\text{) < 1300}\text{sec}{}^{\mathrm{?1}}$.The synergistic effects of flow were also noted when [Ca²⁺] was increased from 4 to 12 mEq, and in the presence of ASA (1 mg/ml), release being less inhibited in the sheared samples. When adrenaline (2.5 μM) was added, the serotonin release, which increased by 26.4%(±3.8%) in 17 controls at the lower thrombin level, was further enhanced by 10.9%(±2.6%) in the paired sheared samples. However, when adrenaline was added after oscillatory flow, the reverse occurred, the sheared samples releasing 8.5% less than the controls.Studies in the aggregometer showed that the rate and extent of aggregation in the sheared samples was a little lower than that in the controls.     

Vasodilator agents and supracollicular transection fail to inhibit cortical spreading depression in the cat

It remains an open question as to whether cortical spreading depression (CSD) is the pathophysiological correlate of the neurological symptoms in migraine with aura. In the experimental animal, CSD is an electrophysiological phenomenon mainly mediated via NMDA receptors. However, according to case reports in humans, visual aura in migraine can be alleviated by vasodilator substances, such as amyl nitrite and isoprenaline. There is also circumstantial evidence that brainstem nuclei (dorsal raphe nucleus and locus coeruleus) may play a pivotal role in the initiation of aura. In this study, CSD was elicited in alpha-chloralose anesthetized cats by cortical needle stab injury and monitored by means of laser Doppler flowmetry. Topical application of isoprenaline (0.1-1%) and amyl nitrite (0.05%) onto the exposed cortex had no effect on the elicitation or propagation of CSD. Also, after supracollicular transection, subsequent CSDs showed no differences in the speed of propagation and associated flow changes. We conclude from these data that--given CSD probably exists in humans during migraine--spreading neurological deficits during migraine aura are independent of brainstem influence and have a primarily neuronal rather than vascular mechanism of generation.     

Decreased brain pathology in organophosphate-exposed rhesus monkeys following benzodiazepine therapy

Two benzodiazepine compounds, midazolam and diazepam, were administered as adjunctive treatment to soman-exposed rhesus monkeys to evaluate their effects on acute soman intoxication. Monkeys were pretreated orally with pyridostigmine, exposed to soman, and treated i.m. with atropine, pralidoxime chloride (2-PAM), and with midazolam, diazepam or sterile water (control). All monkeys that received the benzodiazepines recovered sooner and exhibited no convulsions. Neuronal degenerative and necrotic lesions were decreased or eliminated in the entorhinal cortex, caudate nucleus, and hippocampus of those animals that received benzodiazepine therapy. These findings support the continued evaluation of drugs with anticonvulsant activity as standard adjunct therapy for soman intoxication.