Objective Preliminary assessment of a new instrument, the Brief Traumatic Brain Injury Screen (BTBIS). Design Cross-sectional study of 596 soldiers returning from Iraq and/or Afghanistan, comparing the consistency of their reports of traumatic brain injury (TBI) across instruments with similar TBI questions, and in a brief follow-up interview. Setting Military base. Measures Self-reported probable TBI on the BTBIS and on 2 longer questionnaires, and a brief follow-up interview. Results Self-reports of probable TBI were higher on the BTBIS, than on the longer instruments. Participants who screened positive on the BTBIS generally provided consistent information about probable TBI in the follow-up interview. Conclusions In this initial study, the BTBIS demonstrated promise as part of a triage process in mass casualty situations, permitting individuals with probable TBI to self-report injury and continued symptoms. Further study, including full validation and reliability assessment, is warranted and required before these screening tools can be fully evaluated.

Platelet-activating factor (PAF) and leukotrienes, newly described classes of vasoactive lipids, may play a role in anaphylaxis. It has recently been suggested that the vasoconstrictor effects of PAF in isolated rat lung are related to release of leukotrienes C4 and D4. Thyrotropin-releasing hormone (TRH), a tripeptide, has potent antihypotensive activity in experimental shock, including that resulting from either leukotriene D4 administration or antigen-induced anaphylaxis. We utilized an unanesthetized guinea pig model to study the relationships among PAF, leukotrienes, and TRH and their potential interactions on the cardiovascular system. PAF (1 nmol/600 g body weight i.v.) produced profound hypotension which was completely blocked by TRH (2 mg/kg i.v.). Nafazatrom or FPL 55712, a presumed receptor antagonist of leukotrienes, was ineffective, whereas U-60257, a leukotriene synthesis inhibitor, displayed incomplete blockade. Moreover, leukotriene-like immunoreactivity in plasma did not increase following PAF administration. Thus, hypotension produced by PAF does not appear to result secondarily from release of cysteinyl leukotrienes. Moreover, the ability of TRH to block the hypotensive effects of PAF may partially account for its beneficial effects in experimental anaphylaxis and provides further rationale for the therapeutic evaluation of this peptide in anaphylactic shock.

The cardiorespiratory, sympathetic and biochemical effects of T-2 toxin were examined in conscious rats and guinea pigs. The pithed rat preparation was also used to evaluate possible direct effects of T-2 on the heart and vasculature. Injection of T-2 (0.5-2.0 mg/kg i.v.) into conscious rats produced prolonged (6-8 hr) hypertension and tachycardia, followed by hypotension. Total peripheral resistance was increased and cardiac output decreased. In guinea pigs, a steady decrease in pressure and rate occurred. Intravenous administration of T-2 to pithed rats did not alter blood pressure or heart rate at a time when, in conscious rats, both blood pressure and heart rate were increased. Significant elevations of arterial plasma norepinephrine, epinephrine and dopamine occurred after T-2, with metabolic acidosis, hypocarbia and hyperoxemia in both conscious rats and guinea pigs. In the rat, increase in plasma vasopressin and prostacyclin were elevated, but thromboxane and leukotriene C4-immunoreactivity were not changed. In pithed rats, T-2 did not increase basal or stimulated plasma catecholamines but produced the same changes in blood gases, pH and lactate. The LD50 values for i.v. T-2 in the rat and guinea pig were 0.74 and 1.30 mg/kg, respectively. The data are consistent with the hypothesis that T-2 toxin disrupts cellular aerobic metabolism, resulting in lactic acidosis, sympathoadrenomedullary activation, variable initial circulatory responses and eventual cardiovascular collapse.

Soybean lipoxygenase, an enzyme which catalyzes the formation of the vasoactive lipid 15-hydroperoxy eicosatetraenoic acid (15-HPETE) from arachidonic acid, was administered to unanesthetized guinea pigs previously prepared with indwelling vascular cannulae for continuous cardiovascular monitoring. Administration of this enzyme (150 mg/kg IV) resulted in profound hypotension in this model, but no cardiovascular change was observed after administration of equal weight or equimolar amounts of another protein (ovalbumin). The lipoxygenase-induced hypotension, moreover, was promptly reversed by the peptide thyrotropin-releasing hormone (TRH) (2 mg/kg IV) but not by the opiate receptor antagonist naloxone (2 mg/kg IV). This TRH-naloxone dissociation was comparable to that previously observed in hypotension produced by leukotriene D4 (LTD4), platelet-activating factor (PAF), or antigen-induced anaphylaxis in the same species. Thus, although its properties as a “physiologic” opiate antagonist led to the early trials of TRH in endotoxic, hypovolemic and spinal shock, it is now apparent that TRH reverses several other forms of experimental shock, including that caused by lipoxygenase, through non-endorphin-related mechanism.

Platelet-activating factor (PAF), a vasoactive phospholipid implicated in anaphylactic reactions, causes severe hypotension in experimental animals that is highly resistant to pharmacological therapy. In the present studies, we showed that PAF (1 nmol/600 g body weight, IV) produced profound hypotension in unanesthetized guinea pigs that was promptly and completely reversed by thyrotropin-releasing hormone (TRH) (2 mg/kg, IV) or by the synthetic TRH analog MK771 (2 mg/kg, IV). TRH also reversed this hypotension when administered intracerebroventricularly (ICV) at a dose (0.02 mg/kg) that was systemically ineffective. The opiate receptor antagonist naloxone (5 mg/kg) was less effective than TRH in reversing the cardiovascular consequences of PAF administration. These data suggest that TRH reverses PAF-induced shock through central receptor-mediated mechanisms. This therapeutic action of TRH may partially account for the beneficial cardiovascular effects of this peptide in anaphylactic shock.

In a model of haemorrhagic shock causing the death of all saline-treated rats within 25.8 ± 2.7 min after treatment, the intravenous injection of thyrotropin-releasing hormone tartrate (TRH-T) at the dose of 4 mg/kg induces a prompt and sustained increase of arterial pressure and pulse amplitude, with survival of all rats. Bilateral vagotomy, atropine sulphate (2 mg/kg intraperitoneally) and hemicholinium-3 (20 μg/rat intracerebroventricularly) partially prevent the TRH-T-induced shock reversal, whereas atropine methylbromide has no effect. These data indicate that afferent vagal fibres, brain cholinergic neurons and central muscarinic receptors play a role in the mechanism of the anti-shock effect of TRH-T.

Thyrotropin-releasing hormone (TRH) reversed the hypotension produced by leukotriene D4 (LTD4) (5 micrograms/kg, i.v.) in conscious guinea pigs in a dose-dependent fashion at intravenous doses between 0.2 and 2.0 mg/kg. LTD4 hypotension was also reversed by the synthetic TRH analog MK771 (0.2 or 2 mg/kg, i.v.), suggesting a possible receptor-mediated mechanism. Since LTD4 has been implicated as a mediator of anaphylaxis, these results provide a basis for further evaluation of TRH and its analogs in the treatment of anaphylactic shock.

We have utilized an unanesthetized guinea pig model to study the cardiovascular effects of leukotriene D4 (LTD4), a compound implicated in slow reacting substance of anaphylaxis (SRS-A). Intravenous (IV) administration of LTD4 at 5 micrograms/kg produced profound hypotension, bradycardia, hypoxia and acidosis. The hypotension and bradycardia were rapidly and completely reversed by IV thyrotropin-releasing hormone (TRH) at a dose of 2 mg/kg. In contrast, TRH treatment had no effect on the hypoxia or acidosis induced by LTD4. These data provide a potential physiological link between two distinct classes of endogenous substances and may have implications for the therapy of anaphylactic shock.