Related Experiment Video
Updated: Aug 14, 2026
Dural Stimulation and Periorbital von Frey Testing in Mice As a Preclinical Model of Headache
Published on: July 29, 2021
Mannitol but not dantrolene prevents myocardial dysfunction following intra-cranial hypertension in rats
1Department of Anesthesiology, Queen's University, Kingston, Ontario, Canada.
Insights
Intracranial hypertension causes cardiac issues, but 15% mannitol effectively prevents circulatory collapse in rats. Dantrolene alone did not protect against these cardiac complications.
Area of Science:
- Cardiology
- Neuroscience
- Pharmacology
Background:
- Intracranial hypertension can lead to cardiac complications, potentially due to disrupted intracellular calcium (Ca2+) homeostasis.
- Understanding the mechanisms behind these cardiac issues is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the effects of dantrolene, a sarcoplasmic reticulum (SR) Ca2+ release blocker, on myocardial dysfunction in rats with induced intracranial hypertension.
- To compare the efficacy of dantrolene, mannitol, and Pentaspan in mitigating these complications.
Main Methods:
- Rats were anesthetized and pre-treated with dantrolene (with or without 15% mannitol), 3% or 15% mannitol alone, or Pentaspan.
- Intracranial hypertension was induced using subdural balloon inflation.
- Hemodynamic function, TnI cleavage, and lipid peroxidation were assessed.
Main Results:
- Dantrolene combined with 15% mannitol, or 15% mannitol alone, prevented the hyperdynamic response and circulatory collapse seen with 3% mannitol or Pentaspan.
- Hemodynamic function was preserved regardless of TnI cleavage in the mannitol-treated groups.
- Only high-dose 15% mannitol significantly reduced cardiac lipid peroxidation.
Conclusions:
- 15% mannitol effectively attenuates cardiopulmonary complications associated with intracranial hypertension in rats.
- Dantrolene alone showed no protective effect, suggesting its mechanism is not solely responsible for preventing these cardiac issues.
- Mannitol's protective effects may be linked to its free radical scavenging properties and reduction of oxidative stress.
Abstract:
Cardiac complications stemming from intra-cranial hypertension may result from impaired intra-cellular Ca(2+) homeostasis. The aim of this study was to examine the effects of dantrolene, a blocker of sarcoplasmic reticulum (SR) Ca(2+) release, on myocardial dysfunction associated with intra-cranial hypertension in rats. Dantrolene (10 mg) with and without 15% mannitol was administered to halothane-anesthetized rats prior to induction of intra-cranial hypertension by subdural balloon inflation. Its effects were compared to 3% and 15% mannitol and 5% Pentaspan. Dantrolene with mannitol or 15% mannitol alone prevented the transient intra-cranial hypertension-induced hyperdynamic response and ensuing circulatory collapse that was found in animals pre-treated with 3% mannitol solution or pentaspan. Moreover, hemodynamic function was preserved irrespective of TnI cleavage. However, only animals treated with high dose 15% mannitol exhibited lower lipid peroxidation content in the heart. In contrast, pre-treatment with dantrolene alone did not prevent the cardiac complications associated with intra-cranial hypertension. In conclusion, 15% mannitol attenuated the cardiopulmonary complications associated with intra-cranial hypertension. Dantrolene without mannitol was without effect. Since mannitol exhibits free radical scavenging properties, protection could be the result of a decrease in oxidative stress after intra-cranial hypertension.
