Arteriojugular endothelin-1 gradients in aneurysmal subarachnoid haemorrhage

Abstract

Plasma endothelin (ET) is elevated in patients with vasospasm following subarachnoid haemorrhage (SAH). However, systemic levels provide no indication regarding local production in the brain, and late elevation may be a consequence rather than a cause of vasospasm. We measured arteriojugular (AJ) gradients of ET-1 in 17 patients over the first week after SAH, and related these to the subsequent development of vasospasm. Daily, paired arterial and jugular bulb blood samples were obtained up to seven days post SAH, and assayed for ET-1 using radioimmunoassay. Systemic levels and AJ gradients were compared in patients with and without vasospasm. Significant AJ gradients were observed for ET-1 (P<0.01). These differences remained significant in the subgroup of patients who developed vasospasm (0.12+/-0.05 pmol/l; P<0.05), in whom AJ gradients represented 25+/-7% of systemic levels (0.84+/-0.05 pmol/l). AJ gradients did not reach significance in patients who did not develop vasospasm (0.09+/-0.07 pmol/l; P=0.2). Systemic ET-1 levels and AJ gradients were unrelated to SAH grade, surgical or endovascular interventions, or extracranial complications. AJ gradients in the first week following SAH suggest early production of ET-1 in the cerebrovascular bed. However, early systemic ET-1 levels did not discriminate between patients with and without vasospasm. Larger AJ differences may predict vasospasm, but further work is needed to confirm this observation. AJ gradient measurement may provide a useful technique for investigating the role of other peptides in acute brain injury.

Elevated level of endothelin-1 in cerebrospinal fluid and lack of nitric oxide in basilar arterial plasma associated with cerebral vasospasm after subarachnoid haemorrhage in rabbits

“…These findings might possibly be explained epiphenomenally due to the ET-1 conversion rate in the endothelial basilar arterial layer or due to ET-1 release from the CSF into the cerebral circulation. This hypothesis might also be supported by Menon et al who found high arteriojugularvenous ET-1 gradients in patients suffering from SAH-induced CVS [15].…”

“…[7,8] The controversy is still ongoing although preclinical and clinical trials using intracarotid infusion of NO gas solution, [9] intracarotid or intrathecal administration of NO donors [10][11][12] and ET-1 receptor inhibitors have claimed clinical success. [13,14] However, better understanding of aSAH pathophysiology, discovery of new aSAHrelated events like cortical spreading ischemia [15] and, probably most importantly, the failure of Clazosentan, a selective ET-1 A receptor inhibitor, in Phase II clinical study [2] to improve the outcome despite prevention of vasospasm all lead to a paradigm shift with the focus on the possibility that a stroke after aSAH may be evoked by another nonvasospasm-related mechanism(s). Growing body of evidence suggests that these pathomechanisms are a result of the presence of an arterial blood clot in the subarachnoid space, increased ET-1 in CSF, and decreased availability of NO in cerebral arteries.…”

“…Growing body of evidence suggests that these pathomechanisms are a result of the presence of an arterial blood clot in the subarachnoid space, increased ET-1 in CSF, and decreased availability of NO in cerebral arteries. [2,15] In their clever, well-planned and executed, but most confirmatory in vivo experimental study published in this issue of Acta Neurochirugica , V. Neuschmelting and colleagues simultaneously examined the role of both NO and ET-1 in the development of vasospasm in a rabbit model of aSAH. To assure the relevance of their findings, the authors used an innovative surgical approach.…”

Testing of potential biomarkers of cerebral ischemia and vasospasm in patients with cerebral aneurysm surgery

“…Such an observation is in concordance with current knowledge about endothelin-1 concentrations rising in the first few days after rupture. (28,49,50) At the moment of awakening from general anesthesia, a lower pCO 2 in the jugular vein was found in the group of patients operated on after aneurismal rupture compared to the group operated on for a nonruptured cerebral aneurysm. A similar result was observed if the group of patients with supposed cerebral vasospasm and the group without it were compared, yet only with a borderline statistical significance.…”

Juguloarterial Endothelin-1 Gradients After Severe Traumatic Brain Injury

“…A previously described method [26] for directly measuring mediator synthesis and release in the cerebrovascular bed was used to quantify the arteriovenous gradient of ET-1 and its precursor Big ET-1 across the brain. The venous samples used to make these calculations were obtained from jugular bulb catheters used for brain oximetry; when correctly positioned, these exclusively sample blood drained from the cerebrovascular bed.…”