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Evaluation of the Effectiveness of Dantrolene Sodium against Digoxininduced Cardiotoxicity in Adult Rats
Mahmoud Zardast1, Kosar Behmanesh2, Tahereh Farkhondeh3
1Department of Pathology, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran.
Background:
Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity.
Objective:
The aim of this study was to evaluate the protective effect of dantrolene on digoxininduced cardiotoxicity in male rats.
Methods:
This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n = 6) as follows: Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group, Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group, Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group, Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group, Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals' cavernous sinus and each animal's heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20°C. The heart samples were fixed in formalin 10% for histopathological evaluation.
Results:
K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group (p < 0.001). Dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group (p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group.
Conclusion:
dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene's cardioprotective and cardiotoxic doses in animal models.
Insights
Dantrolene at 10 mg/kg demonstrated cardioprotective effects against digoxin-induced cardiotoxicity in rats. This suggests dantrolene may mitigate heart damage and hyperkalemia associated with digoxin poisoning.
Area of Science:
- Pharmacology
- Cardiovascular Toxicology
- Experimental Medicine
Background:
- Digoxin poisoning is a clinical concern in patients receiving digoxin.
- Dantrolene is being investigated as a potential therapeutic agent for digoxin-induced cardiotoxicity.
Purpose of the Study:
- To assess the protective efficacy of dantrolene against digoxin-induced cardiotoxicity in a male rat model.
Main Methods:
- Wistar rats were divided into seven groups, receiving normal saline, ethanol, dantrolene, digoxin, or combinations thereof.
- Serum electrolytes (K, Na, Ca, Mg) and creatine phosphokinase (CPK) were measured.
- Cardiac tissue underwent histopathological evaluation for signs of damage and inflammation.
Main Results:
- Digoxin administration led to cardiac tissue degeneration and increased potassium levels.
- Dantrolene at 10 mg/kg significantly improved cardiac histology and normalized calcium levels.
- A high dose of dantrolene (20 mg/kg) was associated with increased potassium levels.
Conclusions:
- Dantrolene (10 mg/kg) exhibits cardioprotective properties in a rat model of digoxin toxicity.
- The cardioprotective mechanism may involve mitigating cardiac remodeling and hyperkalemia.
- Further studies are required to establish optimal therapeutic and toxic doses of dantrolene.
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