Protective effects of dantrolene against myocardial injury induced by isoproterenol in rats: Biochemical and histological findings

Purpose: We investigated whether dantrolene might protect the heart against myocardial injury (MI) induced by isoproterenol (ISO), using an experimental model in rats. Methods: Twenty-eight rats were randomized to treatment with saline only (control group, n = 8), ISO only (ISO group, n = 8), low-dose dantrolene (LDD) + ISO (LDD group, n = 6) and high-dose dantrolene (HDD) + ISO (HDD group, n = 6). ISO (150 mg/kg/day, s.c.), LDD (5 mg/kg/day, i.p.) and HDD (10 mg/kg/day, i.p.) were given once a day for two consecutive days. At the end of the second day, blood samples were taken from abdominal aorta shortly after the rats were anesthetised for cardiac troponins T (cTnT) and I (cTnI) assay, and the hearts were removed and observed microscopically. Results: cTnT and cTnI levels were increased in the ISO group when compared with the control group (p < 0.001). LDD and HDD significantly reduced cTnT and cTnI levels when compared with the ISO group. Elevations of cTnT and cTnI appeared to relate to the severity of histological changes. The rate of animals that exhibited marked MI was higher in the ISO group than in the control group (p < 0.001). The rats in both LDD and HDD groups showed less histological changes when compared to the ISO group (p < 0.01). There was no significant difference between the control group and both LDD and HDD groups. Conclusions: This study shows that dantrolene has a significant effect in the protection of the heart against MI induced by ISO. We believe that pretreatment with dantrolene may contribute to developing novel strategies in the cardiotoxicity animal models and in the prevention of the cardiotoxic effects of elevated levels of catecholamines. (c) 2004 Elsevier Ireland Ltd. All rights reserved.