Dantrolene Improves Cerebral Perfusion More than Nimodipine in a Rat Model of Cerebral‐induced Vasospasm

Abstract

A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature, and the primary cause of morbidity and mortality following a hemorrhagic stroke. The middle cerebral artery (MCA) is one of the most common locations affected by CVSPs. Experimental evidence shows that the ryanodine receptor inhibitor dantrolene may be as effective as the Ca+2 channel blocker nimodipine in reducing vasospasms in the systemic vasculature. To determine if this effect also extends to the cerebral vasculature, we used a rat model of cerebral‐induced vasospasms to investigate the effects of intravenously administered dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg) on cerebral blood flow velocity in the MCA. Blood flow velocity was measured in the MCA seven days after vasospasm‐induction, using a PeriFlux 5000 Laser Doppler System. Measurements were performed 30 minutes before and one hour after either dantrolene or nimodipine administration. In addition, hemodynamic parameters (i.e., systolic, diastolic, and mean blood pressures; heart rate) were measured before and after administration of the drugs. Dantrolene decreased MCA blood flow velocity by 35% (from 364.7± 60 to 231.0 ± 34 perfusion units), whereas nimodipine reduced this parameter by only 14% (N=6, P<0.05). For both dantrolene and nimodipine, the hemodynamic parameters remained unchanged (N=6, P>0.05, when compared to results before drug administration). Our results suggest that 2.5 mg/kg dantrolene is more effective than 1 mg/kg nimodipine in reducing vascular reactivity and improving cerebral blood perfusion in the MCA, without altering systemic hemodynamic parameters. Therefore, dantrolene may provide a promising therapy for the management of CVSP and its complications.Support or Funding InformationThis work was supported by Grants from the National Institute of Health (MBRS‐RISE Grant R25GM061838), the NIMHD‐CCRHD‐RCMI Program (U54‐MD007600), and the Anesthesiology Department of the University of Puerto Rico‐School of Medicine.