Transfusion-related acute lung injury secondary to biologically active mediators.

Transfusion-related acute lung injury is seen following the transfusion of blood components. The reported incidence is approximately 1 in 2000 transfusions. Clinically, it is similar to adult respiratory distress syndrome. The pathophysiology is unclear but has been attributed to HLA antibodies, granulocyte antibodies, and more recently to biologically active mediators in stored blood components. We report a case with laboratory evidence that supports the role of biologically active mediators in the pathogenesis of transfusion-related acute lung injury. To our knowledge, the case reported here is the first to use lipid extractions of patient samples to determine that lipid-priming activity was present at the time transfusion-related acute lung injury was identified clinically.

Opiate-serotonin synergism stimulating luteinizing hormone release in estrogen-progesterone-primed ovariectomized rats: mediation by serotonin2 receptors.

A tonic inhibition of LH release by endogenous opiate systems is apparent after administration of opiate antagonists to ovariectomized estrogen-progesterone-primed rats. In the presence of a serotonin agonist, morphine has been found to stimulate LH release in ovariectomized animals. Thus, in the present study the individual effects as well as interactions of the opiate and serotonin (5HT) systems have been examined using morphine and quipazine, respectively, as agonists and ketanserin (5HT2) and methysergide (5HT1 and 5HT2) as antagonists. Rats ovariectomized 2-4 weeks beforehand were primed with estradiol benzoate (15 micrograms; day 0) and progesterone (5 mg; day 2). Serial blood samples were collected from unrestrained rats via a jugular cannula inserted 3 days before, and plasma LH was measured by RIA. Neither morphine (4 mg sulfate) nor quipazine (2 mg/kg) administered iv at 1200 h significantly elevated plasma LH at 1210, 1220, or 1230 h compared to levels at 1200 h, although plasma LH concentrations at these times were significantly greater than those in animals receiving saline at 1200 h. However, injection of both morphine and quipazine at 1200 h greatly augmented LH release at 1210, 1220, and 1230 h compared to the response to either drug alone. The duration of the significant elevation of plasma LH was limited to 10 min by ketanserin (2.5 mg/kg, ip, at 0900 h) and to 20 min by methysergide (10 mg/kg, ip, at 0900 h), suggesting mediation of this response by 5HT2 receptors. These results suggest the possibility of an important interaction between opiate and serotonergic systems in controlling the release of LH and raise the intriguing question of its role, if any, in controlling events of the estrous cycle.

Evidence for multiple serotonergic influences on LH release in ovariectomized rats and for modulation of their relative effectiveness by estrogen.

Both opiates and serotonin (5HT) are known to inhibit LH release in ovariectomized rats, and estrogen has been shown to reverse certain serotonergic effects. Therefore studies were undertaken to compare the effects of morphine and the serotonin agonist 5-methoxy-N,N-dimethyltryptamine (5MEODMT) on LH release in ovariectomized rats with and without estrogen priming. Serial blood samples were collected via jugular cannulae before and 5, 15, 30 and 60 min after intravenous administration of morphine, 5MEODMT or both to rats receiving no pretreatment, or a serotonin receptor antagonist (methysergide, METH; or ketanserin, KET) 60 min earlier. In the absence of estrogen, morphine inhibited LH release, and the response was delayed by METH or abolished by KET, suggesting mediation by serotonin2 (5HT2) receptors. 5MEODMT alone failed to alter the release of LH significantly, but apparently activated both stimulatory and inhibitory serotonergic systems. Blockade of 5HT2 receptors with KET enabled an inhibitory system to prevail. No significant changes in LH concentrations were observed following combined administration of morphine and 5MEODMT. Similarly, in estrogen-primed rats morphine appeared to activate both inhibitory (5HT2) and stimulatory (5HT1) systems, resulting in no net change unless the inhibitory system had been antagonized by KET. Administration of 5MEODMT alone or in combination with morphine resulted in a strong stimulatory effect which appeared to be mediated by 5HT1 receptors. These results suggest the existence of a multiplicity of serotonergic influences on the release of LH in the rat, not only in terms of particular species of 5HT receptors, but also in neuronal connectivity.(ABSTRACT TRUNCATED AT 250 WORDS)