Evaluation of Big Endothelin--1 Concentrations
Evaluation of Big Endothelin--1 Concentrations
Object. Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post-subarachnoid hemorrhage (SAH) vasospasm.
Methods. Serum and CSF concentrations of big endothelin (ET)-1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET-1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET-1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET-1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgery-treated, 1.84±0.83 pg/ml; and embolization-treated 2.19±0.54 pg/ml) and without (microsurgery-treated 1.76±0.61 pg/ml; and embolization-treated 2.01±0.48 pg/ml) delayed infarctions.
Conclusions. Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET-1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET-1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.
Symptomatic cerebral vasospasm remains among the major causes of delayed morbidity and mortality after aneurysmal SAH. Increased ET concentrations have been demonstrated in the CSF and peripheral blood in patients after aneurysmal SAH. Because ETs are among the most potent endogenous vasoconstrictor substances known, they have been implicated in the pathogenesis of vasospasm. 1) Serum and CSF concentrations of ET-1 are elevated after aneurysmal SAH. 2) Intracisternal injection of ET-1 induces sustained cerebral vasoconstriction in experimental animals. 3) Endothelin-1 immunoreactivity in the cerebral vasculature is increased after experimental SAH. 4) The development of delayed-onset vasospasm may coincide with increased CSF concentrations of big ET-1 and ET-1. 5) Endothelin receptor antagonists 6 and ET-converting enzyme inhibitors prevent or reverse vasospasm after experimental SAH.
Studies in which ET concentrations in CSF and peripheral blood after SAH are reported are usually conducted in patients undergoing neurosurgical interventions; that is, levels of ET are measured in the perioperative period. A nonneurosurgical approach might lead to different results. On one hand, one could argue that elevated ET levels may be the consequence of surgically induced disturbances of the cerebral parenchyma and/or vasculature. On the other hand, the amount of subarachnoid blood found in the basal cisterns is highly predictive of the risk for delayed ischemia and infarction. In light of the increasing use of endovascular therapy in the treatment of intracranial aneurysms, one question has emerged: does the inability of endovascular therapy to remove subarachnoid blood prior to cisternal clot lysis result in a higher CSF concentration of potential spasmogens, with the potential for more severe vasospasm?
Big ET-1 is the active precursor substance of mature 21-residue ET-1 and probably provides the best information about the activation of the ET system of patients in the acute phase after SAH. The purpose of the present study was therefore to measure serially serum and CSF concentrations of big ET-1 in a population of patients with SAH receiving on of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgery, 2) early endovascular treatment, or 3) no intervention in the acute phase. Patients undergoing neurosurgical operations were exposed to the highest physiological stress -- craniotomy and microdissection of the cerebral vasculature -- but potentially benefited from the intraoperative removal of a cisternal clot. In patients receiving endovascular treatment there was no disturbance of the cerebral vasculature other than intraluminal microcatheterization, but they also did not undergo cisternal clot removal. In patients receiving only medical treatment in the acute phase no surgery trauma other than ventriculostomy was induced.
Object. Whereas the removal of subarachnoid blood is possible during early-stage aneurysm surgery, this cannot be achieved in aneurysms treated by endovascular means. The levels of potential spasmogens in the cerebrospinal fluid (CSF) in patients receiving endovascular treatment might therefore be higher, with the potential for more severe post-subarachnoid hemorrhage (SAH) vasospasm.
Methods. Serum and CSF concentrations of big endothelin (ET)-1 were serially measured in patients with SAH receiving one of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgical treatment (15 patients), 2) early endovascular treatment (17 patients), or 3) no intervention in the acute phase (12 patients). In patients suffering delayed infarctions higher levels of big ET-1 CSF were demonstrated than in those without infarctions (p = 0.01). In patients in whom surgery was performed in the acute phase lower big ET-1 CSF concentrations were demonstrated than in those who received embolization treatment or no treatment (p = 0.02). Subgroup analysis demonstrated that in patients receiving early endovascular treatment, higher big ET-1 CSF concentrations were revealed than in those undergoing early aneurysm surgery; this was true for patients with (microsurgery-treated, 1.84±0.83 pg/ml; and embolization-treated 2.19±0.54 pg/ml) and without (microsurgery-treated 1.76±0.61 pg/ml; and embolization-treated 2.01±0.48 pg/ml) delayed infarctions.
Conclusions. Among patients with SAH who received treatment during the acute phase, those undergoing early aneurysm surgery were shown to have lower big ET-1 CSF levels than those receiving embolization and no treatment (that is, the nonsurgical treatment groups). The clinical significance of this finding remains to be established in future clinical trials, because in the present study the trend toward lower levels of big ET-1 CSF in the microsurgically treated group was not paralleled by a lower delayed stroke rate or an improvement in neurological outcome.
Symptomatic cerebral vasospasm remains among the major causes of delayed morbidity and mortality after aneurysmal SAH. Increased ET concentrations have been demonstrated in the CSF and peripheral blood in patients after aneurysmal SAH. Because ETs are among the most potent endogenous vasoconstrictor substances known, they have been implicated in the pathogenesis of vasospasm. 1) Serum and CSF concentrations of ET-1 are elevated after aneurysmal SAH. 2) Intracisternal injection of ET-1 induces sustained cerebral vasoconstriction in experimental animals. 3) Endothelin-1 immunoreactivity in the cerebral vasculature is increased after experimental SAH. 4) The development of delayed-onset vasospasm may coincide with increased CSF concentrations of big ET-1 and ET-1. 5) Endothelin receptor antagonists 6 and ET-converting enzyme inhibitors prevent or reverse vasospasm after experimental SAH.
Studies in which ET concentrations in CSF and peripheral blood after SAH are reported are usually conducted in patients undergoing neurosurgical interventions; that is, levels of ET are measured in the perioperative period. A nonneurosurgical approach might lead to different results. On one hand, one could argue that elevated ET levels may be the consequence of surgically induced disturbances of the cerebral parenchyma and/or vasculature. On the other hand, the amount of subarachnoid blood found in the basal cisterns is highly predictive of the risk for delayed ischemia and infarction. In light of the increasing use of endovascular therapy in the treatment of intracranial aneurysms, one question has emerged: does the inability of endovascular therapy to remove subarachnoid blood prior to cisternal clot lysis result in a higher CSF concentration of potential spasmogens, with the potential for more severe vasospasm?
Big ET-1 is the active precursor substance of mature 21-residue ET-1 and probably provides the best information about the activation of the ET system of patients in the acute phase after SAH. The purpose of the present study was therefore to measure serially serum and CSF concentrations of big ET-1 in a population of patients with SAH receiving on of the following treatments: 1) early (within 72 hours of SAH) aneurysm surgery, 2) early endovascular treatment, or 3) no intervention in the acute phase. Patients undergoing neurosurgical operations were exposed to the highest physiological stress -- craniotomy and microdissection of the cerebral vasculature -- but potentially benefited from the intraoperative removal of a cisternal clot. In patients receiving endovascular treatment there was no disturbance of the cerebral vasculature other than intraluminal microcatheterization, but they also did not undergo cisternal clot removal. In patients receiving only medical treatment in the acute phase no surgery trauma other than ventriculostomy was induced.
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