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Is a functional sarcoplasmic reticulum necessary for preconditioning?
1Division of Radiological Sciences, 5th floor, Thomas Guy House, Guy's Hospital, London, UK. alison.cave@kcl.ac.uk
Journal of Molecular and Cellular Cardiology
|March 25, 2000
Summary
Ischemic preconditioning (PC) protects the heart, but its link to sarcoplasmic reticulum (SR) calcium release is unclear. This study shows PC remains protective even when SR calcium handling is impaired, suggesting SR calcium release is not essential for PC's protective effects.
Area of Science:
- Cardiology
- Physiology
- Biochemistry
Background:
- Ischemic preconditioning (PC) offers cardiac protection.
- Reduced calcium release from the sarcoplasmic reticulum (SR) is linked to PC.
- The necessity of SR calcium handling for PC remains unproven.
Purpose of the Study:
- To determine if a functional SR is essential for the protective mechanisms of PC.
- To investigate the role of SR calcium handling in PC-induced cardioprotection.
Main Methods:
- Isolated rat hearts were subjected to normoxic perfusion followed by ischemia/reperfusion protocols.
- SR calcium handling was manipulated using ryanodine (RY) and cyclopiazonic acid (CPA).
- 31P-NMR spectroscopy assessed energy metabolites (ATP, PCr, Pi) and intracellular pH.
Main Results:
- RY and CPA significantly reduced developed pressure, confirming impaired SR calcium handling.
- PC significantly improved left ventricular developed pressure (LVDP) recovery compared to controls.
- PC maintained its protective effect on LVDP recovery even with RY and CPA treatment, indicating SR dysfunction did not abolish protection.
Conclusions:
- Ischemic preconditioning (PC) provides cardiac protection even when sarcoplasmic reticulum (SR) calcium accumulation is inhibited.
- Changes in SR calcium release are not essential for the cardioprotective effects of PC.
- These findings challenge the established role of SR calcium handling in the mechanism of PC.