Calcium, sodium, and the calcium paradox

Area of Science:

• Cardiovascular Physiology
• Cellular Biology
• Pharmacology

Background:

• The calcium paradox describes cell damage during reperfusion after ischemia.
• Understanding ion fluxes, particularly calcium and sodium, is crucial for mitigating this damage.
• Verapamil and nifedipine are calcium channel blockers with potential roles in cardioprotection.

Purpose of the Study:

• To investigate the impact of sodium loading on calcium and sodium gain, and myoglobin loss during the calcium paradox in adult rat hearts.
• To determine the effects of verapamil and nifedipine on these parameters during calcium repletion following calcium-free perfusion.

Main Methods:

• Adult rat hearts were subjected to calcium-free perfusion for varying durations.
• Hearts were then reperfused with calcium-containing solution, with or without sodium loading, verapamil, or nifedipine.
• Measurements included intracellular calcium and sodium content, and myoglobin release.

Main Results:

• Sodium loading did not alter calcium gain or myoglobin loss after prolonged ( > 2 min) calcium-free perfusion.
• Short-term (0.5–1.5 min) calcium-free perfusion led to enhanced calcium gain in sodium-loaded hearts, particularly during early repletion.
• Verapamil and nifedipine significantly slowed early calcium gain but not late calcium gain; verapamil enhanced late calcium gain.
• These drugs abolished early sodium gain but not late sodium gain during repletion.

Conclusions:

• Calcium repletion after calcium-free perfusion involves at least two phases: an early and a late phase.
• The early phase of calcium gain includes both verapamil/nifedipine-sensitive and insensitive components.
• The verapamil/nifedipine-insensitive component of early calcium gain likely involves sodium-calcium exchange.