Plasma endothelin concentrations after aneurysmal subarachnoid hemorrhage

Restricted access

Object. The pathogenesis of cerebral vasospasm and delayed ischemia after subarachnoid hemorrhage (SAH) seems to be complex. An important mediator of chronic vasospasm may be endothelin (ET), with its powerful and long-lasting vasoconstricting activity. In this study the author investigated the correlation between serial plasma concentrations of ET and ischemic symptoms, angiographically demonstrated evidence of vasospasm, and computerized tomography (CT) findings after aneurysmal SAH.

Methods. Endothelin-1 immunoreactivity in plasma was studied in 70 patients with aneurysmal SAH and in 25 healthy volunteers by using a double-antibody sandwich-enzyme immunoassay (immunometric) technique.

On the whole, mean plasma ET concentrations in patients with SAH (mean ± standard error of mean, 2.1 ± 0.1 pg/ml) did not differ from those of healthy volunteers (1.9 ± 0.2 pg/ml). Endothelin concentrations were significantly higher (p < 0.05) in patients who experienced delayed cerebral ischemia with fixed neurological deficits compared with those in other patients (post-SAH Days 0–5, 3.1 ± 0.8 pg/ml compared with 2.1 ± 0.2 pg/ml; post-SAH Days 6–14, 2.5 ± 0.4 pg/ml compared with 1.9 ± 0.2 pg/ml). Patients with angiographic evidence of severe vasospasm also had significantly (p < 0.05) elevated ET concentrations (post-SAH Days 0–5, 3.2 ± 0.8 pg/ml; post-SAH Days 6–14, 2.7 ± 0.5 pg/ml) as did those with a cerebral infarction larger than a lacuna on the follow-up CT scan (post-SAH Days 0–5, 3.1 ± 0.8 pg/ml; post-SAH Days 6–14, 2.5 ± 0.4 pg/ml) compared with other patients. Patients in whom angiography revealed diffuse moderate-to-severe vasospasm had significantly (p < 0.05) higher ET levels than other patients within 24 hours before or after angiography (2.6 ± 0.3 compared with 1.9 ± 0.2 pg/ml). In addition, patients with a history of hypertension or cigarette smoking experienced cerebral infarctions significantly more often than other patients, although angiography did not demonstrate severe or diffuse vasospasm more often in these patients than in others.

Conclusions. Endothelin concentrations seem to correlate with delayed cerebral ischemia and vasospasm after SAH. The highest levels of ET are predictive of the symptoms of cerebral ischemia and vasospasm, and ET may also worsen ischemia in patients with a history of hypertension. Thus, ET may be an important causal or contributing factor to vasospasm, but its significance in the pathogenesis of vasospasm remains unknown.

Article Information

Address reprint requests to: Seppo Juvela, M.D., Department of Neurosurgery, Helsinki University Central Hospital, Topeliuksenkatu 5, FIN-00260, Helsinki 26, Finland. email: seppo.juvela@helsinki.fi.

© AANS, except where prohibited by US copyright law.

Headings

References

1.

Asano TIkegaki ISuzuki Yet al: Endothelin and the production of cerebral vasospasm in dogs. Biochem Biophys Res Commun 159:134513511989Biochem Biophys Res Commun 159:

2.

Battistini BD'Orleans-Juste PSirois P: Endothelins: circulating plasma levels and presence in other biologic fluids. Lab Invest 68:6006281993Lab Invest 68:

3.

Broderick JPBrott TTomsick Tet al: Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage. J Neurosurg 78:1881911993J Neurosurg 78:

4.

Caner HHKwan ALArthur Aet al: Systemic administration of an inhibitor of endothelin-converting enzyme for attenuation of cerebral vasospasm following experimental subarachnoid hemorrhage. J Neurosurg 85:9179221996J Neurosurg 85:

5.

Cosentino FKatušic˘ ZS: Does endothelin-1 play a role in the pathogenesis of cerebral vasospasm? Stroke 25:9049081994Stroke 25:

6.

Cosentino FMcMahon EGCarter JSet al: Effect of endothelin A-receptor antagonist BQ-123 and phosphoramidon on cerebral vasospasm. J Cardiovasc Pharmacol 22 (Suppl 8):S332S3351993J Cardiovasc Pharmacol 22 (Suppl 8):

7.

Créminon CFrobert YHabib Aet al: Enzyme immunometric assay for endothelin using tandem monoclonal antibodies. J Immunol Methods 162:1791921993J Immunol Methods 162:

8.

Dilraj ABotha JHRambiritch Vet al: Levels of catecholamine in plasma and cerebrospinal fluid in aneurysmal subarachnoid hemorrhage. Neurosurgery 31:42511992Neurosurgery 31:

9.

Elliott JPNewell DWLam DJet al: Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg 88:2772841998J Neurosurg 88:

10.

Fisher CMKistler JPDavis JM: Relation of cerebral vasospasm to subarachnoid hemorrhage visualized by computerized tomographic scanning. Neurosurgery 6:191980Neurosurgery 6:

11.

Fogelholm RHernesniemi JVapalahti M: Impact of early surgery on outcome after aneurysmal subarachnoid hemorrhage. A population-based study. Stroke 24:164916541993Stroke 24:

12.

Foley PLCaner HHKassell NFet al: Reversal of subarachnoid hemorrhage-induced vasoconstriction with an endothelin receptor antagonist. Neurosurgery 34:1081131994Neurosurgery 34:

13.

Fujimori AYanagisawa MSaito Aet al: Endothelin in plasma and cerebrospinal fluid of patients with subarachnoid haemorrhage. Lancet 336:6331990 (Letter)Lancet 336:

14.

Hamann GIsenberg EStrittmatter Met al: Absence of elevation of big endothelin in subarachnoid hemorrhage. Stroke 24:3833861993Stroke 24:

15.

Harada TSeto MSasaki Yet al: The time course of myosin light-chain phosphorylation in blood-induced vasospasm. Neurosurgery 36:117811831995Neurosurgery 36:

16.

Hino ATokuyama YKobayashi Met al: Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab 16:6886971996J Cereb Blood Flow Metab 16:

17.

Hino AWeir BKAMacdonald RLet al: Prospective, randomized, double-blind trial of BQ-123 and bosentan for prevention of vasospasm following subarachnoid hemorrhage in monkeys. J Neurosurg 83:5035091995J Neurosurg 83:

18.

Hop JWRinkel GJEAlgra Aet al: Initial loss of consciousness and the risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke 30:226822711999Stroke 30:

19.

Hunt WEHess RM: Surgical risk as related to time of intervention in the repair of intracranial aneurysms. J Neurosurg 28:14201968J Neurosurg 28:

20.

Itoh SSasaki TAsai Aet al: Prevention of delayed vasospasm by an endothelin ETA receptor antagonist, BQ-123: change of ETA receptor mRNA expression in a canine subarachnoid hemorrhage model. J Neurosurg 81:7597641994AA receptor mRNA expression in a canine subarachnoid hemorrhage model. J Neurosurg 81:

21.

Jennett BBond M: Assessment of outcome after severe brain damage. A practical scale. Lancet 1:4804841975Lancet 1:

22.

Juvela S: Aspirin and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Neurosurg 82:9459521995Juvela S: Aspirin and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. J Neurosurg 82:

23.

Juvela S: Cerebral infarction and release of platelet thromboxane after subarachnoid hemorrhage. Neurosurgery 27:9299351990Juvela S: Cerebral infarction and release of platelet thromboxane after subarachnoid hemorrhage. Neurosurgery 27:

24.

Juvela SKaste MHillbom M: Platelet thromboxane release after subarachnoid hemorrhage and surgery. Stroke 21:5665711990Stroke 21:

25.

Kasuya HWeir BShen Yet al: Procollagen types I and III and transforming growth factor-beta gene expression in the arterial wall after exposure to periarterial blood. Neurosurgery 33:7167221993Neurosurgery 33:

26.

Kasuya HWeir BKAWhite DMet al: Mechanism of oxyhemoglobin-induced release of endothelin-1 from cultured vascular endothelial cells and smooth-muscle cells. J Neurosurg 79:8928981993J Neurosurg 79:

27.

Kazuki SOhta TOgawa Ret al: Effects of intraluminal or extraluminal endothelin on perfused rabbit basilar arteries. J Neurosurg 86:8598651997J Neurosurg 86:

28.

Kobayashi HHayashi MKobayashi Set al: Cerebral vasospasm and vasoconstriction caused by endothelin. Neurosurgery 28:6736791991Neurosurgery 28:

29.

Krum HViskoper RJLacourciere Yet al: The effect of an endothelin-receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. N Engl J Med 338:7847901998N Engl J Med 338:

30.

Kwan ALBavbek MJeng AYet al: Prevention and reversal of cerebral vasospasm by an endothelin-converting enzyme inhibitor, CGS 26303, in an experimental model of subarachnoid hemorrhage. J Neurosurg 87:2812861997J Neurosurg 87:

31.

Lam HCTakahashi KGhatei MAet al: Immunoreactive endothelin in human plasma, urine, milk, and saliva. J Cardiovasc Pharmacol 17 (Suppl 7):S390S3931991J Cardiovasc Pharmacol 17 (Suppl 7):

32.

Levin ER: Endothelins. N Engl J Med 333:3563631995Levin ER: Endothelins. N Engl J Med 333:

33.

Lovenberg WMiller RC: Endothelin: a review of its effects and possible mechanisms of action. Neurochem Res 15:4074171990Neurochem Res 15:

34.

Lüscher TF: Endothelin. J Cardiovasc Pharmacol 18 (Suppl 10):S15S221991Lüscher TF: Endothelin. J Cardiovasc Pharmacol 18 (Suppl 10):

35.

Macdonald RL: Cerebral vasospasm. Neurosurg Q 5:73971995Macdonald RL: Cerebral vasospasm. Neurosurg Q 5:

36.

Masaoka HSuzuki RHirata Yet al: Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 2:14021989 (Letter)Lancet 2:

37.

Matsumura YIkegawa RSuzuki Yet al: Phosphoramidon prevents cerebral vasospasm following subarachnoid hemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. Life Sci 49:8418481991Life Sci 49:

38.

Millul VLagente VGillardeaux Oet al: Activation of guinea pig alveolar macrophages by endothelin-1. J Cardiovasc Pharmacol 17 (Suppl 7):S233S2351991J Cardiovasc Pharmacol 17 (Suppl 7):

39.

Nakagomi TKassell NFSasaki Tet al: Etiology of the disruption in blood-arterial wall barrier following experimental subarachnoid hemorrhage. Surg Neurol 34:16261990Surg Neurol 34:

40.

Nirei HHamada KShoubo Fet al: An endothelin ETA receptor antagonist, FR139317, ameliorates cerebral vasospasm in dogs. Life Sci 52:186918741993ALife Sci 52:

41.

Ohlstein EHStorer BL: Oxyhemoglobin stimulation of endothelin production in cultured endothelial cells. J Neurosurg 77:2742781992J Neurosurg 77:

42.

Öhman JServo AHeiskanen O: Risk factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study. J Neurosurg 74:14201991J Neurosurg 74:

43.

Papadopoulos SMGilbert LLWebb RCet al: Characterization of contractile responses to endothelin in human cerebral arteries: implications for cerebral vasospasm. Neurosurgery 26:8108151990Neurosurgery 26:

44.

Peltonen SJuvela SKaste Met al: Hemostasis and fibrinolysis activation after subarachnoid hemorrhage. J Neurosurg 87:2072141997J Neurosurg 87:

45.

Pluta RMBoock RJAfshar JKet al: Source and cause of endothelin-1 release into cerebrospinal fluid after subarachnoid hemorrhage. J Neurosurg 87:2872931997J Neurosurg 87:

46.

Roux SLöffler BMGray GAet al: The role of endothelin in experimental cerebral vasospasm. Neurosurgery 37:78861995Neurosurgery 37:

47.

Seifert VLöffler BMZimmermann Met al: Endothelin concentrations in patients with aneurysmal subarachnoid hemorrhage. Correlation with cerebral vasospasm, delayed ischemic neurological deficits, and volume of hematoma. J Neurosurg 82:55621995J Neurosurg 82:

48.

Shigeno TClozel MSakai Set al: The effect of bosentan, a new potent endothelin receptor antagonist, on the pathogenesis of cerebral vasospasm. Neurosurgery 37:87911995Neurosurgery 37:

49.

Shigeno TMima TYanagisawa Met al: Possible role of endothelin in the pathogenesis of cerebral vasospasm. J Cardiovasc Pharmacol 17 (Suppl 7):S480S4831991J Cardiovasc Pharmacol 17 (Suppl 7):

50.

Shigeno TMima TYanagisawa Met al: Prevention of cerebral vasospasm by actinomycin D. J Neurosurg 74:9409431991J Neurosurg 74:

51.

Shinyama HUchida TKido Het al: Phosphoramidon inhibits the conversion of intracisternally administered big endothelin-1 to endothelin-1. Biochem Biophys Res Commun 178:24301991Biochem Biophys Res Commun 178:

52.

Sobey CGFaraci F: Subarachnoid haemorrhage: what happens to the cerebral arteries? Clin Exp Pharmacol Physiol 25:8678761998Clin Exp Pharmacol Physiol 25:

53.

Suzuki HSato SSuzuki Yet al: Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage. Ann Med 22:2332361990Ann Med 22:

54.

Suzuki NMatsumoto HKitada Cet al: A sensitive sandwich-enzyme immunoassay for human endothelin. J Immunol Methods 118:2452501989J Immunol Methods 118:

55.

Suzuki RMasaoka HHirata Yet al: The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. J Neurosurg 77:961001992J Neurosurg 77:

56.

Vigne PFrelin C: Endothelins activate phospholipase A2 in brain capillary endothelial cells. Brain Res 651:34234419942 in brain capillary endothelial cells. Brain Res 651:

57.

Vorkapic PBevan RDBevan JA: Longitudinal time course of reversible and irreversible components of chronic cerebrovasospasm of the rabbit basilar artery. J Neurosurg 74:9519551991J Neurosurg 74:

58.

Wanebo JEArthur ASLouis HGet al: Systemic administration of the endothelin-A receptor antagonist TBC 11251 attenuates cerebral vasospasm after experimental subarachnoid hemorrhage: dose study and review of endothelin-based therapies in the literature on cerebral vasospasm. Neurosurgery 43:140914181998Neurosurgery 43:

59.

Weir B: The pathophysiology of cerebral vasospasm. Br J Neurosurg 9:3753901995Weir B: The pathophysiology of cerebral vasospasm. Br J Neurosurg 9:

60.

Weir BKAKongable GLKassell NFet al: Cigarette smoking as a cause of aneurysmal subarachnoid hemorrhage and risk for vasospasm: a report of the Cooperative Aneurysm Study. J Neurosurg 89:4054111998J Neurosurg 89:

61.

Yamakawa KPeterson JWSibilia Ret al: Effect of vasoconstrictor agents on diacylglycerol content of normal and vasospastic canine basilar arteries in vitro. Neurosurgery 36:7897961995Neurosurgery 36:

62.

Yamaura ITani EMaeda Yet al: Endothelin-1 of canine basilar artery in vasospasm. J Neurosurg 76:991051992J Neurosurg 76:

63.

Yanagisawa MKurihara HKimura Set al: A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:4114151988Nature 332:

64.

Yang ZRichard Vvon Segesser Let al: Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm? Circulation 82:1881951990Circulation 82:

65.

Zimmermann MSeifert V: Endothelin and subarachnoid hemorrhage: an overview. Neurosurgery 43:8638761998Neurosurgery 43:

66.

Zimmermann MSeifert VLöffler BMet al: Prevention of cerebral vasospasm after experimental subarachnoid hemorrhage by RO 47-0203, a newly developed orally active endothelin receptor antagonist. Neurosurgery 38:1151201996Neurosurgery 38:

67.

Zuccarello MBoccaletti RRomano Aet al: Endothelin B receptor antagonists attenuate subarachnoid hemorrhage-induced cerebral vasospasm. Stroke 29:192419291998Stroke 29:

68.

Zuccarello MSoattin GBLewis AIet al: Prevention of subarachnoid hemorrhage-induced cerebral vasospasm by oral administration of endothelin receptor antagonists. J Neurosurg 84:5035071996J Neurosurg 84:

TrendMD

Cited By

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 8 8 6
Full Text Views 67 67 32
PDF Downloads 76 76 24
EPUB Downloads 0 0 0

PubMed

Google Scholar