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Dantrolene: effects on abnormal intracellular Ca(2+) handling and inotropy in postinfarcted rat myocardium
Jiang-Yong Min1, Achim Meissner, Xin Feng
1Cardiovascular Division, Beth Israel Deaconess Medical Center, and Harvard Medical School, Boston, MA 02215, USA.
Abstract:
The present study was designed to investigate the effects of dantrolene on intracellular Ca(2+) ([Ca(2+)](i)) handling and inotropy in rat infarcted myocardium. Dantrolene-treated rats with myocardial infarction were placed into two different dosage groups. The infarcted control group received placebo only. Isometric contractility and intracellular Ca(2+) transients were recorded simultaneously in isolated papillary muscles. Diastolic [Ca(2+)](i) was significantly lower in muscle preparations from infarcted rats receiving dantrolene compared to the placebo control group. Additionally, treatment with dantrolene in infarcted rats significantly improved the inotropic response to 10(-4) M isoproterenol. The protein levels of the sarcoplasmic reticulum Ca(2+) ATPase were increased in infarcted rat hearts with dantrolene treatment. We conclude that dantrolene improved the inotropic response to beta-adrenoceptor stimulation in rat postinfarcted myocardium, which is related to improved intracellular Ca(2+) handling, and lowered diastolic Ca(2+) concentration.
Insights
Dantrolene treatment in rats with myocardial infarction improved heart muscle function by enhancing calcium handling. This intervention lowered diastolic calcium levels and improved the response to beta-adrenoceptor stimulation.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- Myocardial infarction (MI) leads to impaired cardiac function.
- Altered intracellular calcium ([Ca2+]i) handling is a key feature of post-MI hearts.
- Therapeutic strategies to improve calcium handling are crucial for post-MI recovery.
Purpose of the Study:
- To investigate the effects of dantrolene on intracellular calcium handling and inotropy in a rat model of myocardial infarction.
- To determine if dantrolene can ameliorate cardiac dysfunction following infarction.
Main Methods:
- Rats with induced myocardial infarction were divided into dantrolene-treated groups and a placebo control group.
- Isometric contractility and intracellular calcium transients were measured in isolated papillary muscles.
- Protein levels of sarcoplasmic reticulum Ca2+ ATPase were analyzed.
Main Results:
- Dantrolene treatment significantly reduced diastolic intracellular calcium ([Ca2+]i) in infarcted rat myocardium.
- The inotropic response to isoproterenol was significantly improved in dantrolene-treated infarcted rats.
- Protein levels of sarcoplasmic reticulum Ca2+ ATPase were elevated following dantrolene treatment.
Conclusions:
- Dantrolene improves the inotropic response to beta-adrenoceptor stimulation in post-infarcted rat myocardium.
- Enhanced intracellular calcium handling, including lowered diastolic [Ca2+]i, underlies dantrolene's beneficial effects.
- Dantrolene represents a potential therapeutic agent for managing cardiac dysfunction after myocardial infarction.