Canadian Journal of Anesthesia

, Volume 49, Issue 4, pp 427–433 | Cite as

Isoflurane does not further impair microvascular vasomotion in a rat model of subarachnoid hemorrhage

  • Kyung W. Park
  • Hai B. Dai
  • Caroline Metais
  • Mark E. Comunale
  • Frank W. Sellke
Neuroanesthesia and Intensive Care



Since isoflurane is known to attenuate endotheliumdependent dilation (EDD) in normal cerebral arterioles, we examined whether the anesthetic has a similar effect and further impairs EDD in vessels exposed to SAH.


Autologous blood was introduced in the subarachnoid space and the parietal lobe harvested. Control animals were sacrificed without introduction of blood. The response of microvessies to the endothelium-dependent dilator adenosine diphosphate (ADP) 10−9–10−4 M, the endothelium-independent dilator nitroprusside 10−9–10−4 M, and ET-1 10−13–10−8 M was measured by videomicroscopy in the presence of 0–2 minimum alveolar concentration (MAC) of isoflurane.


Isoflurane attenuated EDD to ADP in control vessels [66 ± 5% (control) vs 27 ± 11% (2 MAC) dilation to ADP 10−4 M, P < 0.05], Although SAH was associated with reduced dilation to ADP exposure to isoflurane did not further impair dilation to ADP after SAH [26 ± 3% (SAH) vs 21 ± 5% (SAH/2 MAC) dilation to ADP 10−4 M,P = NS]. Dilation to nitroprusside was not affected by isoflurane or SAH. Constriction to ET-1 was reduced by 2 MAC ofisoflurane[21 ± 1% (control) vs 13 ± 5% (2 MAC) constriction to ET-1 10−8 M,P < 0.05], but not by I MAC of isoflurane in control vessels. Constriction to ET-1 was greatly attenuated by 1 or 2 MAC of isoflurane after SAH [32 ± 5% (SAH) vs 18 ± 4% (SAH/2 MAC) constriction to ET-1 10−8 M,P < 0.05],


In rats, isoflurane does not further impair EDD after SAH and modulates the constrictive response to ET-1. Such an effect of isoflurane would not predispose the SAH-exposed vessels to vasospasm.


Isoflurane Subarachnoid Hemorrhage Cerebral Vasospasm Minimum Alveolar Concentration Cerebral Microvessels 
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L’isoflurane ne produit pas d’altération subséquente sur la vasomotricité microvasculaire d’un modèle d’hémorragie sous-arachnoïdienne chez le rat



L’isofurane est connu pour atténuer la dilatation dépendante de l’endothélium (DDE) dans les artérioles cérébrales normales. Nous avons vérifié si l’anesthésique a un effet similaire, et s’il affecte davantage la DDE, dans les vaisseaux sanguins exposés à l’hémorragie sous-arachnoïdienne (HSA).


Du sang autologue a été introduit dans l’espace sousarachnoïdien et le lobe pariétal a été prélevé. Les animaux témoins ont été sacrifiés sans introduction de sang. La réaction des microvaisseaux à 10−9–10−4 M d’adénosine diphosphate (ADP), à 10−9–10−4 M de nitroprussiate (deux dilatateurs dépendants de l’endothélium) et à 10−13–10−8 M de ET-1 a été mesurée par vidéomicroscopie en présence d’une concentration alvéolaire minimale (CAM) de 0–2 d’isoflurane.


L’isoflurane a diminué la DDE liée à l’ADP dans les vaisseaux témoins [66 ± 5 % (témoin) vs 27 ± 11 % (2 CAM) de dilatation à 10−4 M d’ADP, P < 0,05]. Bien que l’HSA soit associée à une dilatation réduite liée à l’ADP, l’exposition à l’isoflurane n’a pas accentué la dilatation liée à l’ADP à la suite d’une HSA [26 ± 3 % (HSA) vs 21 ± 5% (HSA/2 CAM) de dilatation à 10−4 M d’ADP, P = NS]. La dilatation liée au nitroprussiate n’a pas été modifiée par l’isofurane ou l’HSA. La constriction liée à l’ET-1 a été réduite par 2 CAM d’isofurane [21 ± 1 % (témoin)vs 13 ± 5%(2 CAM) de constriction à 10−8 M d’ET-1, P < 0,05], mais non par 1 CAM d’isofurane dans les vaisseaux témoins. La constriction liée à l’ET-1 a été grandement atténuée par 1 ou 2 CAM d’isofurane après une HSA [32 ±5% (HSA) vs 18 ± 4% (HSA/2 CAM) de constriction à 10−8 M d’ET-1, P < 0,05].


Chez les rats, l’isofurane ne produit pas d’altération subséquente de la DDE à la suite d’une HSA et il module la réaction constrictive liée à l’ET-1. Cet effet de l’isofurane ne prédisposerait pas au vasospasme les vaisseaux exposés à l’HSA.


  1. 1.
    Sundt TM Jr, Whisnant JP. Subarachnoid hemorrhage from intracranial aneurysms. Surgical management and natural history of disease. N Engl J Med 1978; 299: 116–22.PubMedGoogle Scholar
  2. 2.
    Brawley BW, Strandness DE Jr, Kelly WA. The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg 1968; 28: 1–8.PubMedGoogle Scholar
  3. 3.
    Delgado TJ, Brismar J, Svendgaard NA. Subarachnoid haemorrhage in the rat: angiography and fluorescence microscopy of the major cerebral arteries. Stroke 1985; 16: 595–602.PubMedGoogle Scholar
  4. 4.
    Ohkuma H, Manabe H, Tanaka M, Suzuki S. Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke 2000; 31: 1621–7.PubMedGoogle Scholar
  5. 5.
    Park KW, Metais C, Dai HB, Comunale ME, Sellke FW. Microvascular endothelial dysfunction and its mechanism in a rat model of subarachnoid hemorrhage. Anesth Analg 2001; 92: 990–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Zuo Z, Tichotsky A, Johns RA. Halothane and isoflurane inhibit vasodilation due to constitutive but not inducible nitric oxide synthase. Anesthesiology 1996; 84: 1156–65.PubMedCrossRefGoogle Scholar
  7. 7.
    Jing M, Bina S, Verma A, Hart JA, Muldoon SM. Effects of halothane and isoflurane on carbon monoxideinduced relaxations in the rat aorta. Anesthesiology 1996; 85: 347–54.PubMedCrossRefGoogle Scholar
  8. 8.
    Park KW, Dai HB, Lowenstein E, Darvish A, Sellke FW. Isoflurane and halothane attenuate endotheliumdependent vasodilation in rat coronary microvessels. Anesth Analg 1997; 84: 278–84.PubMedCrossRefGoogle Scholar
  9. 9.
    Park KW, Dai HB, Lowenstein E, Stamler A, Sellke FW. Effect of isoflurane on the β-adrenergic and endothelium-dependent relaxation of pig cerebral microvessels after cardiopulmonary bypass. Journal of Stroke and Cerebrovascular Diseases 1998; 7: 168–78.PubMedCrossRefGoogle Scholar
  10. 10.
    Cole DJ, Nary JC, Reynolds LW, Patel PM, Drummond JC. Experimental subarachnoid hemorrhage in rats. Effect of intravenous — diaspirin crosslinked hemoglobin on hypoperfusion and neuronal death. Anesthesiology 1997; 87: 1486–93.PubMedCrossRefGoogle Scholar
  11. 11.
    Park KW, Dai HB, Lowenstein E, Sellke FW. Vasomotor responses of rat coronary arteries to isoflurane and halothane depend on preexposure tone and vessel size. Anesthesiology 1995; 82: 1323–30.CrossRefGoogle Scholar
  12. 12.
    Vitez TS, White PF, Eger EI, II. Effects of hypothermia on halothane MAC and isoflurane MAC in the rat. Anesthesiology 1974; 41: 80–1.PubMedGoogle Scholar
  13. 13.
    Farber NE, Harkin CP, Niedfeldt J, Hudetz AG, Kampine JP, Schmeling WT. Region-specific and agentspecific dilation of intracerebral microvessels by volatile anesthetics in rat brain slices. Anesthesiology 1997; 87: 1191–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Newman B, Gelb AW, Lam AM. The effect of isoflurane-induced hypotension on cerebral blood flow and cerebral metabolic rate for oxygen in humans. Anesthesiology 1986; 64: 307–10.PubMedCrossRefGoogle Scholar
  15. 15.
    Madsen JB, Cold GE, Hansen ES, Bardrum B, Kruse-Larsen C Cerebral blood flow and metabolism during isoflurane-induced hypotension in patients subjected to surgery for cerebral aneurysms. Br J Anaesth 1987; 59: 1204–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Hansen TD, Warner DS, Todd MM, Vust LJ. The role of cerebral metabolism in determining the local cerebral blood flow effects of volatile anesthetics: evidence for persistent flow-metabolism coupling. J Cereb Blood Flow Metab 1989; 9: 323–8.PubMedGoogle Scholar
  17. 17.
    Kuroda Y, Murakami M, Tsuruta J, Murakawa T, Sakabe T. Preservation of the ratio of cerebral blood flow/metabolic rate for oxygen during prolonged anesthesia with isoflurane, sevoflurane, and halothane in humans. Anesthesiology 1996; 84: 555–61.PubMedCrossRefGoogle Scholar
  18. 18.
    Wei HM, Weiss HR, Sinha AK, Chi OZ. Effects of nitric oxide synthase inhibition on regional cerebral blood flow and vascular resistance in conscious and isoflurane-anesthetized rats. Anesth Analg 1993; 77: 880–5.PubMedCrossRefGoogle Scholar
  19. 19.
    McPherson RW, Kirsch JR, Moore LE, Traystman RJ. N-nitro-L-arginine methyl ester prevents cerebral hyperemia by inhaled anesthetics in dogs. Anesth Analg 1993; 77: 891–7.PubMedCrossRefGoogle Scholar
  20. 20.
    Todd MM, Wu B, Warner DS, Maktabi M. The doserelated effects of nitric oxide synthase inhibition on cerebral blood flow during isoflurane and pentobarbital anesthesia. Anesthesiology 1994; 80: 1128–36.PubMedCrossRefGoogle Scholar
  21. 21.
    Bederson JB, Levy AL, Ding WH, et al. Acute vasoconstriction after subarachnoid hemorrhage. Neurosurgery 1998; 42: 352–62.PubMedCrossRefGoogle Scholar
  22. 22.
    Hambrecht R, Wolf A, Gielen S, et al. Effect of exercise on coronary endothelial function in patients with coronary artery disease. N Engl J Med 2000; 342: 454–60.PubMedCrossRefGoogle Scholar
  23. 23.
    Takahashi K, Ohyanagi M, Ikeoka K, Iwasaki T. Acetylcholine-induced response of coronary resistance arterioles in cholesterol-fed rabbits. Jpn J Pharmacol 1999; 81: 156–62.PubMedCrossRefGoogle Scholar
  24. 24.
    Vallejo S, Angulo J, Peiró C, et al. Highly glycated oxyhaemoglobin impairs nitric oxide relaxations in human mesenteric microvessels. Diabetologia 2000; 43: 83–90.PubMedCrossRefGoogle Scholar
  25. 25.
    Joles JA, Stroes ESG, Rabelink TJ. Endothelial function in proteinuric renal disease. Kidney Int 1999; 56(Suppl 71):S57–61.CrossRefGoogle Scholar
  26. 26.
    Matta BF, Heath KJ, Tipping K, Summors AC. Direct cerebral vasodilatory effects of sevoflurane and isoflurane. Anesthesiology 1999; 91: 677–80.PubMedCrossRefGoogle Scholar
  27. 27.
    Flynn NM, Buljubasic N, Bosnjak ZJ, Kampine JP. Isoflurane produces endothelium-independent relaxation in canine middle cerebral arteries. Anesthesiology 1992; 76: 461–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Jensen NF, Todd MM, Kramer DJ, Leonard PA, Warner DS. A comparison of the vasodilating effects of halothane and isoflurane on the isolated rabbit basilar artery with and without intact endothelium. Anesthesiology 1992; 76: 624–34.PubMedCrossRefGoogle Scholar
  29. 29.
    Ringaert KRA, Mutch WAC, Malo LA. Regional cerebral blood flow and response to carbon dioxide during controlled hypotension with isoflurane anesthesia in the rat. Anesth Analg 1988; 67: 383–8.PubMedCrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2002

Authors and Affiliations

  • Kyung W. Park
    • 1
  • Hai B. Dai
    • 2
  • Caroline Metais
    • 2
  • Mark E. Comunale
    • 1
  • Frank W. Sellke
    • 2
  1. 1.Department of Anesthesia and Critical Care GroupBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA
  2. 2.Department of and SurgeryBeth Israel Deaconess Medical Center, Harvard Medical SchoolBostonUSA

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