Dantrolene mediates vasorelaxation in cerebral vasoconstriction: a case series.
BACKGROUND
Cerebral vasoconstriction syndromes such as vasospasm after subarachnoid hemorrhage (SAH) and trauma, or Call-Fleming syndrome are difficult to treat, and can lead to substantial disability and death. Dantrolene, a ryanodine receptor antagonist, inhibits intracellular calcium release from the sarco-endoplasmic reticulum. We examined the effect of dantrolene on middle cerebral artery (MCA) blood flow velocities as measured by transcranial Doppler (TCD).


METHODS
Three consecutive patients with elevated MCA TCD velocities receiving dantrolene (2.5 mg/kg i.v. q6h) were retrospectively reviewed. Average MCA peak systolic, mean flow velocities, and the pulsatility index (PI) before and after the dantrolene infusion were compared within patients. Systemic physiological parameters (blood pressure, heart rate, central venous pressure, intracranial pressure, body temperature, and cooling water temperature) were retrospectively collected 6 h before and after the dantrolene infusion.


RESULTS
MCA peak systolic velocities (mean +/- SE) for the three patients were 297 +/- 3, 248 +/- 8, and 268 +/- 19 cm/s before dantrolene and 159 +/- 9, 169 +/- 8, and 216 +/- 12 cm/s after dantrolene. Average mean flow velocities showed the same trend. Interestingly, the PI increased slightly from 0.6, 0.52, and 0.67 before dantrolene, to 1.17, 0.71, and 0.77 after dantrolene. Systemic physiological parameters remained stable in all three patients.


CONCLUSIONS
Dantrolene attenuated cerebral vasoconstriction as measured by TCD without altering systemic physiological parameters. This suggests that intracellular calcium release from ryanodine channels in smooth muscle might play a role in vasospasm. A prospective study is underway to test this hypothesis.
Muehlschlegel
Susanne
S
Department of Neurology, University of Massachusetts Medical School, Worcester, MA, USA.
Rordorf
Guy
G
Bodock
Michael
M
Sims
John R
JR
D000328:Adult; D003620:Dantrolene / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects*; D009125:Muscle Relaxants, Central / Q000494:pharmacology* / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000000981:diagnostic imaging / Q000628:therapy; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D020301:Vasospasm, Intracranial / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology
D009125:Muscle Relaxants, Central; D003620:Dantrolene