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Comparative Study of Vasodilatation After Intra-arterial Nicardipine or Dantrolene Infusion in Animal Model of Cerebral Vasospasm

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Abstract

Purpose

Intra-arterial (IA) infusion of calcium channel blockers (CCBs) has been widely applied in treating medically refractory vasospasm; however, surprisingly little is known regarding their vasodilatory duration. This study was undertaken to compare attributes of nicardipine and dantrolene, focusing on efficacy and capacity for sustained vasodilation.

Methods

In New Zealand white rabbits (N = 22), vasospasm was individually provoked through experimentally induced subarachnoid hemorrhage and confirmed via conventional angiography, grouping animals by IA-infused drug (nicardipine vs. dantrolene). Controls received normal saline. After chemoangioplasty, follow-up angiography was performed at intervals of 1–3 h for 6 h to compare vasospastic and dilated (i.e., treated) arterial diameters. Drug efficacy, duration of action, and changes in mean arterial pressure (relative to baseline) were analyzed by group.

Results

Compared with controls, effective vasodilation was evident in both nicardipine and dantrolene test groups after IA infusion. Vasodilatory effects of nicardipine peaked at 1 h, returning to former vasospastic states at 3 h. In dantrolene recipients, vasodilation endured longer, lasting >6 h. Only the nicardipine group showed a significant 3‑h period of lowered blood pressure.

Conclusion

Unlike the vasodilatory action of a CCB, sustained for < 3 h after IA infusion, the effect of dantrolene endured for > 6 h. This outcome suggests that IA dantrolene infused alone or together with a conventional CCB infusion may be a new means of prolonging vasodilatory effect. Further research is needed to assess durations of IA-infused vasodilatory drug based on perfusion status.

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References

  1. Allen GS, Ahn HS, Preziosi TJ, Battye R, Boone SC, Boone SC, Chou SN, Kelly DL, Weir BK, Crabbe RA, Lavik PJ, Rosenbloom SB, Dorsey FC, Ingram CR, Mellits DE, Bertsch LA, Boisvert DP, Hundley MB, Johnson RK, Strom JA, Transou CR. Cerebral arterial spasm--a controlled trial of nimodipine in patients with subarachnoid hemorrhage. N Engl J Med. 1983;308:619–24.

    Article  CAS  Google Scholar 

  2. Connolly ES Jr, Rabinstein AA, Carhuapoma JR, Derdeyn CP, Dion J, Higashida RT, Hoh BL, Kirkness CJ, Naidech AM, Ogilvy CS, Patel AB, Thompson BG, Vespa P; American Heart Association Stroke Council; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Nursing; Council on Cardiovascular Surgery and Anesthesia; Council on Clinical Cardiology. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a guideline for healthcare professionals from the American Heart Association/american Stroke Association. Stroke. 2012;43:1711–37.

    Article  Google Scholar 

  3. Hejčl A, Cihlář F, Smolka V, Vachata P, Bartoš R, Procházka J, Cihlář J, Sameš M. Chemical angioplasty with spasmolytics for vasospasm after subarachnoid hemorrhage. Acta Neurochir (Wien). 2017;159:713–20.

    Article  Google Scholar 

  4. Feng L, Fitzsimmons BF, Young WL, Berman MF, Lin E, Aagaard BD, Duong H, Pile-Spellman J. Intraarterially administered verapamil as adjunct therapy for cerebral vasospasm: safety and 2-year experience. AJNR Am J Neuroradiol. 2002;23:1284–90.

    Google Scholar 

  5. Hoh BL, Ogilvy CS. Endovascular treatment of cerebral vasospasm: transluminal balloon angioplasty, intra-arterial papaverine, and intra-arterial nicardipine. Neurosurg Clin N Am. 2005;16:501–16, vi.

    Article  Google Scholar 

  6. Hänggi D, Turowski B, Beseoglu K, Yong M, Steiger HJ. Intra-arterial nimodipine for severe cerebral vasospasm after aneurysmal subarachnoid hemorrhage: influence on clinical course and cerebral perfusion. AJNR Am J Neuroradiol. 2008;29:1053–60.

    Article  CAS  Google Scholar 

  7. Keuskamp J, Murali R, Chao KH. High-dose intraarterial verapamil in the treatment of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2008;108:458–63.

    Article  CAS  Google Scholar 

  8. Kumar A, Phalak M. Is intra arterial nimodipine really beneficial in vasospasm following aneurysmal subarachnoid hemorrhage? Br J Neurosurg. 2017;31:290.

    Article  Google Scholar 

  9. Lele A, Lyon T, Pollack A, Husmann K, Reeves A. Intra-arterial nicardipine for the treatment of cerebral vasospasm in postpartum cerebral angiopathy: a case study and review of literature. Int J Neurosci. 2011;121:537–42.

    Article  CAS  Google Scholar 

  10. Godfraind T, Miller RC. Specificity of action of Ca++ entry blockers. A comparison of their actions in rat arteries and in human coronary arteries. Circ Res. 1983;52(2 Pt 2):I81–91.

    CAS  Google Scholar 

  11. Huang RQ, Jiang FG, Feng ZM, Wang TY. Nicardipine in the treatment of aneurysmal subarachnoid haemorrhage: a meta-analysis of published data. Acta Neurol Belg. 2013;113:3–6.

    Article  Google Scholar 

  12. Jansen I, Tfelt-Hansen P, Edvinsson L. Comparison of the calcium entry blockers nimodipine and flunarizine on human cerebral and temporal arteries: role in cerebrovascular disorders. Eur J Clin Pharmacol. 1991;40:7–15.

    Article  CAS  Google Scholar 

  13. Katz AM, Leach NM. Differential effects of 1,4-dihydropyridine calcium channel blockers: therapeutic implications. J Clin Pharmacol. 1987;27:825–34.

    Article  CAS  Google Scholar 

  14. Linfante I, Delgado-Mederos R, Andreone V, Gounis M, Hendricks L, Wakhloo AK. Angiographic and hemodynamic effect of high concentration of intra-arterial nicardipine in cerebral vasospasm. Neurosurgery. 2008;63:1080–6; discussion 1086–7.

    Article  Google Scholar 

  15. Lim J, Cho YD, Kwon HJ, Byoun SH, Koh HS, Park B, Choi SW. Duration of Vasodilatory Action After Intra-arterial Infusions of Calcium Channel Blockers in Animal Model of Cerebral Vasospasm. Neurocrit Care. 2021;34:867–75.

    Article  CAS  Google Scholar 

  16. Ortiz Torres MJ, Jahngir M, Qualls K, Litofsky NS, Nattanmai P, Qureshi AI. Intra-Arterial Dantrolene for Refractory Cerebral Vasospasm in Patients with Aneurysmal Subarachnoid Hemorrhage. World Neurosurg. 2019;125:247–52.

    Article  Google Scholar 

  17. Yui H, Imaizumi U, Beppu H, Ito M, Furuya M, Arisaka H, Yoshida K. Comparative effects of verapamil, nicardipine, and nitroglycerin on myocardial ischemia/reperfusion injury. Anesthesiol Res Pract. 2011;2011:521084. https://doi.org/10.1155/2011/521084.

    Article  CAS  Google Scholar 

  18. Toshima M, Kassell NF, Sasaki T, Tanaka Y, Machi T. The effect of hemoglobin on vasodilatory effect of calcium antagonists in the isolated rabbit basilar artery. J Neurosurg. 1992;76:670–8.

    Article  CAS  Google Scholar 

  19. Tallarico RT, Pizzi MA, Freeman WD. Investigational drugs for vasospasm after subarachnoid hemorrhage. Expert Opin Investig Drugs. 2018;27:313–24.

    Article  CAS  Google Scholar 

  20. Aslan A, Cemek M, Buyukokuroglu ME, Altunbas K, Bas O, Yurumez Y, Cosar M. Dantrolene can reduce secondary damage after spinal cord injury. Eur Spine J. 2009;18:1442–51.

    Article  Google Scholar 

  21. Neylon CB, Richards SM, Larsen MA, Agrotis A, Bobik A. Multiple types of ryanodine receptor/Ca2+ release channels are expressed in vascular smooth muscle. Biochem Biophys Res Commun. 1995;215:814–21.

    Article  CAS  Google Scholar 

  22. Román M, Ramírez JM, Morales M, Crespo MJ. Significant reduction of vascular reactivity with dantrolene and nimodipine in diabetic rats: a potential approach to cerebral vasospasm management in diabetes. Pharmacol Rep. 2020;72:126–34.

    Article  Google Scholar 

  23. Navedo MF, Takeda Y, Nieves-Cintrón M, Molkentin JD, Santana LF. Elevated Ca2+ sparklet activity during acute hyperglycemia and diabetes in cerebral arterial smooth muscle cells. Am J Physiol Cell Physiol. 2010;298:C211–20.

    Article  CAS  Google Scholar 

  24. Salomone S, Soydan G, Moskowitz MA, Sims JR. Inhibition of cerebral vasoconstriction by dantrolene and nimodipine. Neurocrit Care. 2009;10:93–102.

    Article  CAS  Google Scholar 

  25. Torres BB, Caldeira FM, Gomes MG, Serakides R, de Marco Viott A, Bertagnolli AC, Fukushima FB, de Oliveira KM, Gomes MV, de Melo EG. Effects of dantrolene on apoptosis and immunohistochemical expression of NeuN in the spinal cord after traumatic injury in rats. Int J Exp Pathol. 2010;91:530–6.

    Article  CAS  Google Scholar 

  26. Flewellen EH, Nelson TE, Jones WP, Arens JF, Wagner DL. Dantrolene dose response in awake man: implications for management of malignant hyperthermia. Anesthesiology. 1983;59:275–80.

    Article  CAS  Google Scholar 

  27. Majidi S, Grigoryan M, Tekle WG, Qureshi AI. Intra-arterial dantrolene for refractory cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Neurocrit Care. 2012;17:245–9.

    Article  Google Scholar 

  28. Sabouri M, Momeni M, Khorvash F, Rezvani M, Tabesh H. The Effect of a Single dose Dantrolene in Patients with Vasospasm Following Aneurysmal Subarachnoid Hemorrhage. Adv Biomed Res. 2017;6:83.

    Google Scholar 

  29. Muehlschlegel S, Rordorf G, Sims J. Effects of a single dose of dantrolene in patients with cerebral vasospasm after subarachnoid hemorrhage: a prospective pilot study. Stroke. 2011;42:1301–6.

    Article  CAS  Google Scholar 

  30. Muehlschlegel S, Carandang R, Hall W, Kini N, Izzy S, Garland B, Ouillette C, van der Bom IM, Flood TF, Gounis MJ, Weaver JP, Barton B, Wakhloo AK. Dantrolene for cerebral vasospasm after subarachnoid haemorrhage: a randomised double blind placebo-controlled safety trial. J Neurol Neurosurg Psychiatry. 2015;86:1029–35.

    Article  Google Scholar 

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Acknowledgements

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. NRF-2020R1F1A1075087).

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Authors and Affiliations

  1. Department of Neurosurgery, Chungnam National University Sejong Hospital, Chungnam National University School of Medicine, Daejeon, Korea (Republic of)

    Jeongwook Lim & Hyoung Soo Byoun

  2. Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, 03080, Seoul, Korea (Republic of)

    Young Dae Cho

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  1. Jeongwook Lim
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Correspondence to Young Dae Cho.

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J. Lim, Y.D. Cho and H.S. Byoun declare that they have no competing interests.

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Lim, J., Cho, Y.D. & Byoun, H.S. Comparative Study of Vasodilatation After Intra-arterial Nicardipine or Dantrolene Infusion in Animal Model of Cerebral Vasospasm. Clin Neuroradiol 32, 1011–1017 (2022). https://doi.org/10.1007/s00062-022-01151-4

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