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Gadolinium prevents stretch-mediated contractile dysfunction in isolated papillary muscles
A C Nicolosi1, C S Kwok, S J Contney
1Department of Surgery, The Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA. nicolosi@mcw.edu
American Journal of Physiology. Heart and Circulatory Physiology
|February 17, 2001
Summary
Overstretching the heart muscle can cause dysfunction through stretch-activated (SA) ion channels, not L-type calcium channels. Blocking SA channels prevents this negative effect, highlighting their role in cardiac contractility.
Area of Science:
- Cardiology
- Physiology
- Molecular Biology
Background:
- Myocardial stretch is a critical factor influencing cardiac contractility.
- The role of stretch-activated (SA) ion channels in cardiac dysfunction remains incompletely understood.
- L-type calcium channels are known to be involved in cardiac excitation-contraction coupling.
Purpose of the Study:
- To investigate the hypothesis that myocardial overstretching induces or exacerbates contractile dysfunction via SA ion channels.
- To differentiate the role of SA channels from L-type calcium channels in mechanical stretch-induced cardiac abnormalities.
- To examine the impact of overstretching on cardiac contractility under normal and modified hypoxia-reoxygenation (MHR) conditions.
Main Methods:
- Guinea pig papillary muscles were subjected to physiological stretch, overstretch, or unloaded conditions for 85 minutes.
- Contractile force (maximum developed tension, T(max)) was measured and normalized.
- The effects of Gd(3+) (SA channel antagonist) and nifedipine (L-type calcium channel antagonist) were assessed during overstretching and MHR.
Main Results:
- Overstretched muscles showed significantly decreased contractile force compared to physiological and unloaded controls.
- Gd(3+) administration prevented the contractile dysfunction caused by overstretching.
- Nifedipine did not prevent the decrease in contractility due to overstretching.
- Overstretching exacerbated contractile dysfunction during MHR, an effect mitigated by Gd(3+) but not nifedipine.
Conclusions:
- Myocardial overstretching contributes to contractile abnormalities through SA channels.
- These SA channels are distinct from L-type calcium channels involved in cardiac function.
- Targeting SA channels may offer a therapeutic strategy for managing stretch-induced cardiac dysfunction.