Release of glutamate and of free fatty acids in vasogenic brain edema

✓ The pathophysiological potential of mediator substances in manifestations of secondary brain damage is attracting increased attention. This is particularly true of the excitatory transmitters glutamate and arachidonic acid. Noxious properties of these compounds in central nervous tissue have been demonstrated. The current study was performed to determine whether glutamate and arachidonate are released in brain tissue secondary to focal trauma. For this purpose, a cold injury of exposed cerebral cortex was induced in cats. Marked accumulation of glutamate was observed in interstitially drained edema fluid, reaching 10 to 15 times the level that was assessed in normal cerebrospinal fluid (CSF) prior to trauma. The extracellular release of glutamate was further dramatically enhanced by a critical decrease of the cerebral perfusion pressure due to a malignant increase of intracranial pressure. Under these conditions, glutamate concentrations 1000 to 1500 times normal levels accumulated in vasogenic edema fluid, demonstrating a relationship between the extent of the release of glutamate in damaged brain and the severity of the insult. Although under normal conditions glutamate concentrations in plasma were considerably higher than in the interstitial fluid, the pronounced increase of glutamate in this compartment due to trauma cannot be explained by transport of the compound together with the plasma-like edema from the intravascular space. Corresponding findings were obtained for free fatty acid concentrations in edema fluid. Almost all fatty acids that were studied had a significantly higher concentration in edema fluid than in normal CSF obtained as a control prior to trauma. However, contrary to the findings for glutamate, fatty acid concentrations in edema fluid were lower than in plasma. Accumulation of fatty acids in vasogenic edema fluid might, therefore, have resulted from uptake of the material together with edema fluid through the breached blood-brain barrier. Arachidonic acid was an exception. Its concentrations were significantly higher in edema fluid than in plasma, suggesting that it was released from cerebral parenchyma as the underlying mechanism of its extracellular accumulation. The current observations provide further support for a mediator function of glutamate and arachidonic acid in acute traumatic lesions of the brain. Quantitative assessment of the release of highly active mediator substances in brain tissue may facilitate analysis of the therapeutic efficiency of specific treatment aimed at interfering with the release or pathological function of mediators of secondary brain damage.

Platelet Activation In Coronary System Of Patients With Coronary Artery Stenosis (CAS)

Platelets and platelet mediator substances are thought to play a role in the genesis of atheroma and spasm of coronary arteries. In the present study, indices of platelet activation (PA) were studied in the basal state and under conditions of exercise [Pacing (P) ; Handgrip (HG)] in patients with CAS and controls (CO). Pat, and methods; 22 pat. (14 with CAS > 75% in angiography; 8 with normal coronary arteries). No premedication, heparin or contrast media; Judkins technique; simultaneous sampling in the sinus coronarius (CS) and in the aorta (A) (basal, 5 min. P, 3 min. HG). Measurements: Platelet counts (PC), Beta-thromboglobulin (B-TG), platelet factor 4 (PF 4) with RIA, thromboxane B2 (RIA), ADP/collagen induced platelet aggregation (MA). Results : In the basal state no difference between A and CS was demonstrable for CO and CAS with respect to any of the above parameters. Both after P and during HG, a significant (p < 0.05) increase of B-TG was found in CAS; however, a significant increase was found in CO. In contrast to literature, no change of PC was observed. However, under P and HG a significant decrease of collagen and ADP-induced platelet aggregation (p< 0.05) was observed in CAS but not in CO. In some, but not all, CAS-patients, elevated TXB2 was demonstrable in A and CS blood. Conclusion: The present study demonstrates PA in the coronary system of pat. with CAS. Reduced aggregability but no change of PC may be due to subthreshold activation in proximity to the stenosis. This study (which avoided the use of heparin and contrast agents) also shows that PA, as measured by local sampling, is neither a sensitive nor a specific indicator of CAS.

Pharmacological studies on the pulmonary vein of the horse. I. Effects of selected spasmogens

Horses suffer from a respiratory condition, similar to human allergic asthma, that is characterized by severe dyspnea, wheezing, coughing, and mucus production. Mediator substances released during the allergic reaction may contract airways and pulmonary vasculature. Nothing is known of the effects of autacoids and other vasoactive substances on equine pulmonary vessels. Therefore, spiral strips of equine pulmonary vein were prepared in vitro and the effects of histamine (H), 5-hydroxytryptamine (5HT), bradykinin (Bk), carbachol (Carb), and phenylephrine (Phen) were studied. The order of contractile effectiveness for the agonists on the vein was found to be 5HT > H> Bk > Phen > Carb, although H consistently produced the greatest maximal effects. H1-receptors appeared to mediate H contractions while H2-receptors had no measurable effect. 5HT responses were mediated directly by 'D-type' smooth muscle receptors. Bk produced contractions but of a lesser magnitude than either H or 5HT. Varying degrees of tachyphylaxis were observed for each agent. α-Adrenergic receptor stimulation by Phen initiated low-magnitude contractions whereas Carb exhibited virtually no activity on the pulmonary vein. Contractile responses of pulmonary veins to various spasmogens may contribute to the equine asthmatic response by raising vascular hydrostatic pressure, thereby enhancing edema formation.

Immune Reactions of Human Blood Platelets

SummaryThe effect on human platelets of 2 endotoxin preparations (one had known Shwartzman-activity in rabbits, the other was not tested for its biological activity) was investigated in vitro. The following results were found:1. Endotoxin has no effect on washed human platelets suspended in isotonic, plasmafree buffer solution.2. Aggregation or release of adenine nucleotides from human platelets by endotoxin does also not occur if the platelets are suspended in coagulable, complement active, pooled human plasma or plasma fractions.3. Platelets pretreated with α-chymotrypsin do not show aggregation or release of nucleotides by endotoxin.4. The ability of human platelets to retract a fibrin clot is not disturbed by endotoxin. This excludes a functional platelet injury by endotoxin not detectable by aggregation or nucleotide release.5. There is no evidence for the assumption that the effect of endotoxin on platelets is transmitted by yet hypothetical, platelet-damaging mediator substances from leukocytes.6. These results suggest that an immunological injury of platelets by endotoxin comparable with the effect of immune complexes or aggregated gammaglobulin is highly improbable.