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. 2008 Apr 10;9(3):177–180. doi: 10.1007/s10194-008-0034-x

Intracranial hemodynamics during intravenous infusion of glyceryl trinitrate

H K Iversen 1, S Holm 2, L Friberg 2, P Tfelt-Hansen 1,✉
PMCID: PMC3476195  PMID: 18401549

Abstract

The mechanisms of glyceryl trinitrate (GTN)-induced headache are not fully elucidated. In this study we administered GTN 0.5 μg/kg/min i.v. for 20 min in six healthy volunteers. Before, during and 60 min after the infusion, we investigated regional cerebral blood flow (rCBF), cerebral blood volume (CBV), both estimated with SPECT, and blood flow velocity (BFV) in the middle cerebral artery (MCA), measured with transcranial Doppler. Headache was scored on a numerical verbal rating (0–10) scale. rCBF was unchanged, CBV was slightly increased (13%) during GTN infusion, whereas BFV decreased both during (20%) and 60 min (15%) after GTN. Headache was short-lived and maximal during infusion. This discrepancy of time-effect curves for the effect of GTN on headache and dilatation of MCA indicates that MCA is most likely not the primary source of pain in GTN-induced headache. The time-effect curves for the effect of GTN on headache and on dilation of MCA differed markedly. This indicates that MCA is most likely not the primary source of pain in GTN-induced headache.

Keywords: Glyceryl trinitrate, Headache, Cerebral blood flow, Cerebral blood volume, Transcranial Doppler

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Acknowledgments

Conflict of interest

None.

References

  • 1.Iversen HK, Olesen J, Tfelt-Hansen P. Intravenous nitroglycerin as an experimental model of vascular headache. Basic characteristics. Pain. 1989;38:17–24. doi: 10.1016/0304-3959(89)90067-5. [DOI] [PubMed] [Google Scholar]
  • 2.Thomsen LL, Kruuse C, Iversen HK, Olesen J. A nitric oxide donor (nitroglycerin) induce genuine migraine attacks. Eur J Neurol. 1994;1:73–80. doi: 10.1111/j.1468-1331.1994.tb00053.x. [DOI] [PubMed] [Google Scholar]
  • 3.Olesen J, Iversen HK, Thomsen LL. Nitric oxide supersensitivity. A possible molecular mechanism of migraine pain. Neuroreport. 1993;4:1027–1030. doi: 10.1097/00001756-199308000-00008. [DOI] [PubMed] [Google Scholar]
  • 4.Olesen J, Thomsen LL, Iversen HK. Nitric oxide is a key molecule in migraine and other vascular headaches. Trends Pharmacol Sci. 1994;15:149–153. doi: 10.1016/0165-6147(94)90075-2. [DOI] [PubMed] [Google Scholar]
  • 5.Iversen HK, Olesen J. Headache induced by a nitric oxide donor (nitroglycerin) responds to sumatriptan. A human model for development of migraine drugs. Cephalalgia. 1996;16:412–418. doi: 10.1046/j.1468-2982.1996.1606412.x. [DOI] [PubMed] [Google Scholar]
  • 6.Schmetterer L, Wolzt M, Krejcy K, Graselli U, Findl O, Eichler H-G, Singer EA. Cerebral and ocular hemodynamic effects of sumatriptan in the nitroglycerin headache model. Clin Pharmacol Ther. 1996;60:199–205. doi: 10.1016/S0009-9236(96)90136-8. [DOI] [PubMed] [Google Scholar]
  • 7.Tvedskov JF, Thomsen LL, Iversen H, Gibson A, Wiliams P, Olesen J. The prophylactic effect of valproate on glyceryltrinitrate induced migraine. Cephalalgia. 2004;24:576–585. doi: 10.1111/j.1468-2982.2003.00720.x. [DOI] [PubMed] [Google Scholar]
  • 8.Tvedskov JF, Thomsen LL, Iversen HK, Williams P, Gibson A, Jenkins K, Peck R, Olesen J. The effect of propranolol on glyceryltrinitate-induced headache and arterial response. Cephalalgia. 2004;24:1076–1087. doi: 10.1111/j.1468-2982.2004.00796.x. [DOI] [PubMed] [Google Scholar]
  • 9.Tvedskov JF, Iversen HK, Olesen J. A double-blind study of SB-220453 (Tonerbasat) in the glyceryl trinitrate (GTN) model of migraine. Cephalalgia. 2004;24:875–882. doi: 10.1111/j.1468-2982.2004.00762.x. [DOI] [PubMed] [Google Scholar]
  • 10.Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, Goadsby PJ. A PET study exploring the laterality of brainstem activation in migraine using glyceryl trinitrate. Brain. 2005;128:932–939. doi: 10.1093/brain/awh416. [DOI] [PubMed] [Google Scholar]
  • 11.Aaslid R, Markwalder TM, Nomes H. Noninvasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg. 1982;57:769–774. doi: 10.3171/jns.1982.57.6.0769. [DOI] [PubMed] [Google Scholar]
  • 12.Thomsen LL, Iversen HK. Experimental and biological variation of three-dimensional transcranial Doppler measurements. J Appl Physiol. 1993;75:2805–2810. doi: 10.1152/jappl.1993.75.6.2805. [DOI] [PubMed] [Google Scholar]
  • 13.Celsis P, Goldman T, Henriksen L, Lassen NA. A method for calculating regional cerebral blood flow from emission computed tomography of inert gas concentrations. J Comput Assist Tomogr. 1981;5:641–645. doi: 10.1097/00004728-198110000-00006. [DOI] [PubMed] [Google Scholar]
  • 14.Holm S, Friberg L, Iversen HK, Lassen NA. Dual energy SPECT-methods and applications. In: Schmidt HAE, Chambron J, editors. Nuclear Medicines: Quantitative analysis in imaging and function. Stuttgart: Schattauer; 1990. pp. 11–13. [Google Scholar]
  • 15.Fletcher A, McLoone P, Bulpitt C. Quality of life on angina therapy: A randomized controlled trial of transdermal glyceryl trinitrate against placebo. Lancet. 1988;II:4–8. doi: 10.1016/S0140-6736(88)92942-X. [DOI] [PubMed] [Google Scholar]
  • 16.Noonan PK, Benet LZ. Incomplete and delayed bioavailability of sublingual nitroglycerin. Am J Cardiol. 1985;55:184–187. doi: 10.1016/0002-9149(85)90325-X. [DOI] [PubMed] [Google Scholar]
  • 17.Thomsen LL, Iversen HK, Brinck TA, Olesen J. Arterial supersensitivity to nitric oxide (nitroglycerin) in migraine sufferers. Cephalalgia. 1993;13:395–399. doi: 10.1046/j.1468-2982.1993.1306395.x. [DOI] [PubMed] [Google Scholar]
  • 18.Iversen HK, Reuter U. Nitric oxide involvement in migraine. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA, editors. The headaches. 3rd ed. Philadelphia: Lippincott; 2006. pp. 281–287. [Google Scholar]
  • 19.Parson AA. Nitric oxide. In: Olesen J, Goadsby PJ, Ramadan NM, Tfelt-Hansen P, Welch KMA, editors. The headaches. 3rd ed. Philadelphia: Lippincott; 2006. pp. 151–158. [Google Scholar]
  • 20.Olesen J, Friberg L, Olsen TS, Iversen HK, Lassen NA, Andersen AR, Karle A. Timing and topography of cerebral blood flow, aura, and headache during migraine attacks. Ann Neurol. 1990;28:791–798. doi: 10.1002/ana.410280610. [DOI] [PubMed] [Google Scholar]
  • 21.Dahl A, Russell D, Nyberg-Hansen R, Rootwell K. Effect of nitroglycerin on cerebral circulation measured by transcranial Doppler and SPECT. Stroke. 1989;20:1733–1736. doi: 10.1161/01.str.20.12.1733. [DOI] [PubMed] [Google Scholar]
  • 22.White RP, Deane C, Hindley C, Bloomfield PM, Cunningham VJ, Vallance P, et al. The effect of the nitric oxide donor glyceryl trinitrate on global and regional cerebral blood flow in man. J Neurol Sci. 2000;178:23–28. doi: 10.1016/S0022-510X(00)00357-9. [DOI] [PubMed] [Google Scholar]
  • 23.Bednarczyk EM, Wack DS, Kassab MY, Burch K, Trinidad K, Haka M, Gona J. Brain blood flow in the nitroglycerin (GTN) model of migraine: measurement using positron emission tomography and transcranial Doppler. Cephalalgia. 2002;22:749–757. doi: 10.1046/j.1468-2982.2002.00440.x. [DOI] [PubMed] [Google Scholar]
  • 24.Toftgard KE, Ahlner J. Mechanism of action of nitrates. Cardiovasc Drugs Ther. 1994;8:701–707. doi: 10.1007/BF00877117. [DOI] [PubMed] [Google Scholar]
  • 25.Heyck H. Neue Beiträge zur Klinik und Pathogenese der Migräine. Stuttgart: Thieme Verlag; 1956. [Google Scholar]
  • 26.Friedman AP (1972) Current concepts in the diagnosis and treatment of chronic recurring headache. Symposium on Clinical Neurology. Med Clin North Am 1257–1271 [DOI] [PubMed]
  • 27.Chou CH, Chao AC, Lu SP, Hu HH, Wang SJ. Cephalic venous congestion aggravates only migraine-like type headaches. Cephalalgia. 2004;24:973–979. doi: 10.1111/j.1468-2982.2004.00781.x. [DOI] [PubMed] [Google Scholar]
  • 28.Doepp F, Schreiber SJ, Dreier JP, Einhäupl KM, Valduza JM. Migraine aggravation by cephalic venous congestion. Headache. 2003;43:96–98. doi: 10.1046/j.1526-4610.2003.03024.x. [DOI] [PubMed] [Google Scholar]
  • 29.Daugaard D, Olesen J. No relation between cephalic venous dilatation and pain in migraine. J Neurol Neurosurg Psychiatr. 1998;65:260–262. doi: 10.1136/jnnp.65.2.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Friberg L, Olesen J, Iversen HK, Sperling B. Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet. 1991;338:13–17. doi: 10.1016/0140-6736(91)90005-A. [DOI] [PubMed] [Google Scholar]
  • 31.Tegeler CH, Davidai G, Gengo FM, Kappertz VA, Troost BT, Gabriel H, Davis RL. Middle cerebral artery velocity correlates with nitroglycerin-induced headache onset. J Neuroimaging. 1996;6:81–86. doi: 10.1111/jon19966281. [DOI] [PubMed] [Google Scholar]
  • 32.Kruuse C, Jacobsen TB, Lassen LH, Thomsen LL, Hasselbach SG, Dige-Petersen H, Olesen J. Dipyridamole dilates large cerebral arteries concomitant to headache induction in healthy subjects. J Cereb Blood Flow Metab. 2000;20:1372–1379. doi: 10.1097/00004647-200009000-00012. [DOI] [PubMed] [Google Scholar]
  • 33.Kruuse C, Thomsen LL, Birk S, Olesen J. Migraine can be induced by sildenafil without changes in middle cerebral artery. Brain. 2003;126:241–247. doi: 10.1093/brain/awg009. [DOI] [PubMed] [Google Scholar]

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