clazosentan and Hypothermia

Systemic inflammatory response syndrome (SIRS) may develop after aneurysmal subarachnoid hemorrhage (SAH). We investigated factors associated with SIRS after SAH, whether SIRS was associated with complications of SAH such as vasospasm, cerebral infarction, and clinical outcome, and whether SIRS could contribute to a difference in outcome between patients treated by endovascular coiling or neurosurgical clipping of the ruptured aneurysm.. This was exploratory analysis of 413 patients in the CONSCIOUS-1 study. SIRS was diagnosed if the patient had at least 2 of 4 variables (hypothermia/fever, tachycardia, tachypnea, and leukocytosis/leukopenia) within 4 days of admission. Clinical outcome was measured on the Glasgow outcome scale 3 months after SAH. The relationship between clinical and radiologic variables and SIRS, angiographic vasospasm, delayed ischemic neurologic deficit (DIND), cerebral infarction, vasospasm-related infarction, and clinical outcome were modeled with uni- and multivariable analyses.. 63% of patients developed SIRS. Many factors were associated with SIRS in univariate analysis, but only poor WFNS grade and pneumonia were independently associated with SIRS in multivariable analysis. SIRS burden (number of SIRS variables per day over the first 4 days) was associated with poor outcome, but not with angiographic vasospasm, DIND, or cerebral infarction. The method of aneurysm treatment was not associated with SIRS.. SIRS was associated with poor outcome but not angiographic vasospasm, DIND, or cerebral infarction after SAH in the CONSCIOUS-1 data. There was no support for the notion that neurosurgical clipping is associated with a greater risk of SIRS than endovascular coiling.

Topics: Adult; Cerebral Infarction; Databases as Topic; Dioxanes; Double-Blind Method; Female; Fever; Humans; Hypothermia; Leukocytosis; Male; Middle Aged; Placebos; Pyridines; Pyrimidines; Receptor, Endothelin A; Subarachnoid Hemorrhage; Sulfonamides; Systemic Inflammatory Response Syndrome; Tachycardia; Tetrazoles; Treatment Failure; Treatment Outcome; Vasospasm, Intracranial

The aim of the present study was to investigate whether endothelin-1 (ET-1) in cerebral arteries is inhibited by the new, non-peptidergic ET(A) receptor antagonist Ro 61-1790 and, if it is, whether that inhibition reduces the lesion volume induced by cold injury in the parietal cortex. In vitro experiments were performed by measuring the isometric contractions of the rat middle cerebral and basilar arteries. A cold lesion was induced in vivo by the application of a pre-cooled (-78 degrees C) copper cylinder (diameter 3 mm) to the intact dura of rats for 6 s. After 24 h, lesion volume was determined by the triphenyltetrazolium method. In vitro, ET-1 (10(-12) - 3x10(-7) M) caused a dose-dependent contraction under resting conditions in the middle cerebral and basilar arteries of control rats. Ro 61-1790 (3x10(-9) M, 10(-7) M) shifted the concentration-effect curves for ET-1 in a parallel fashion (Emax unaltered). Post-treatment with Ro 61-1790 (10(-7)-10(-5) M) also inhibited the prior contraction elicited by ET-1 (3x10(-9) M) significantly. In vitro ET-1 application 3 h after the intracerebroventricular in vivo administration of Ro 61-1790 showed that the antagonist had reached the arteries and was bound to their ET(A) receptors. Intracerebroventricular pre-treatment of Ro 61-1790 reduced significantly the lesion volume by 23% after the injury. We conclude that ET-1 is involved in the development of secondary brain damage and that intracerebroventricular treatment with Ro 61-1790 reduces the size of the brain lesion caused by cold injury.

Topics: Animals; Basilar Artery; Cold Temperature; Dioxanes; Endothelin Receptor Antagonists; Endothelin-1; Hypothermia; Injections, Intraventricular; Male; Middle Cerebral Artery; Parietal Lobe; Pyridines; Pyrimidines; Rats; Rats, Wistar; Receptor, Endothelin A; Sulfonamides; Tetrazoles; Vasoconstriction