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Enhanced sodium-calcium exchange in the infarcted heart: effects on sarcoplasmic reticulum content and cellular
Sheldon E Litwin1, Dongfang Zhang
1Division of Cardiology, Salt Lake City Veterans Affairs Medical Center and the University of Utah, Salt Lake City, Utah 84148, USA. sheldon.litwin@hsc.utah.edu
Insights
Congestive heart failure impairs heart muscle function. In a rabbit model, reduced heart contractions were linked to poor calcium release synchronization, not low sarcoplasmic reticulum calcium stores.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Congestive heart failure (CHF) is associated with high mortality and morbidity.
- Arrhythmias and contractile dysfunction are key complications of CHF.
- Cellular calcium (Ca2+) handling abnormalities are implicated in both conditions.
Purpose of the Study:
- To investigate the role of sarcoplasmic reticulum (SR) Ca2+ content and Ca2+ transient dynamics in a rabbit model of post-myocardial infarction left ventricular dysfunction.
Main Methods:
- Utilized a rabbit model of myocardial infarction to induce left ventricular dysfunction.
- Assessed myocyte sarcoplasmic reticulum Ca2+ content at various stimulation rates.
- Evaluated intracellular Ca2+ transient amplitude and synchronization.
Main Results:
- Myocyte SR Ca2+ content was found to be normal or increased at slow stimulation rates in the rabbit model.
- Prolonged action potential duration may enhance Ca2+ influx via the Na+/Ca2+ exchanger.
- Reduced amplitude of intracellular Ca2+ transients and contractions occurred despite preserved SR Ca2+ content, due to impaired Ca2+ release synchronization.
Conclusions:
- In this model of CHF, impaired myocyte contractility is not solely due to reduced SR Ca2+ stores.
- Dyssynchronous Ca2+ release within myocytes significantly contributes to contractile dysfunction.
- Understanding these Ca2+ handling mechanisms is crucial for developing targeted therapies for heart failure.
Abstract:
Arrhythmias and contractile dysfunction both contribute to the high morbidity and mortality in patients with congestive heart failure. Contractile dysfunction is generally believed to reflect a decrease in the amplitude of intracellular Ca(2+) transients, whereas tachyarrythmias are often initiated in the setting of cellular Ca(2+) overload. In a rabbit model of left ventricular dysfunction due to myocardial infarction, we found evidence that myocyte sarcoplasmic reticulum Ca(2+) content may be normal or even increased at slow stimulation rates. This may occur because prolonged action potential duration promotes Ca(2+) influx via the Na(+)/Ca(2+) exchanger. Despite preserved SR Ca(2+) content, intracellular Ca(2+) transients and contractions may be reduced in amplitude because of impaired synchronization of Ca(2+) release events throughout the myocyte.