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Published on: October 28, 2014
Effects of low extracellular calcium on cytosolic calcium and ischemic contracture
E Jimenez1, P del Nido, M Sarin
1Department of Surgery, University of Illinois, Chicago.
Insights
Low extracellular calcium reduces myocardial contracture during ischemia. This intervention attenuates the rise in intracellular calcium, delaying injury and decreasing contracture force in rabbit hearts.
Area of Science:
- Cardiovascular Physiology
- Ischemic Heart Disease Research
- Calcium Homeostasis
Background:
- Myocardial cytosolic calcium ([Cai]) increases during ischemia, preceding irreversible contracture.
- Membrane-bound calcium stores are depleted concurrently with the [Cai] rise.
Purpose of the Study:
- To investigate the effect of low extracellular calcium ([Cao]) on ischemia-induced myocardial contracture.
- To determine if low [Cao] can mitigate the detrimental rise in intracellular calcium during ischemia.
Main Methods:
- Isolated retroperfused rabbit hearts subjected to 37°C ischemia.
- Perfusion with low extracellular calcium (100 μM) versus normal calcium (2.45 mM).
- Measurement of intracellular calcium ([Cai]) using Fura-2 AM fluorescent indicator.
Main Results:
- Low [Cao] perfusate significantly decreased peak contracture pressure.
- Low [Cao] delayed the onset and peak of ischemic contracture.
- In normal calcium, [Cai] rose >50% during ischemia; in low [Cao], [Cai] was attenuated and delayed.
Conclusions:
- Low extracellular calcium (100 μM) attenuates ischemia-induced intracellular calcium rise.
- Pre-ischemic low calcium perfusion delays contracture onset and reduces its force.
- This suggests a protective role for low extracellular calcium in preventing irreversible ischemic injury.
Abstract:
We have shown that myocardial cytosolic calcium [Cai] rises during ischemia. Simultaneously membrane bound stores are depleted. The [Cai] rise precedes the onset of irreversible ischemic contracture. We found that a low extracellular calcium [Cao] (100 microM) perfusate decreased peak contracture pressure and delayed the time to onset and to peak of ischemic contracture in the isolated retroperfused rabbit heart subjected to 37 degrees C ischemia. [Cai] was measured with the intracellular [Cai] fluorescent indicator Fura-2 AM (10 microM) in a separate group. In the group exposed to 2.45 mM Ca2+ there was a significant rise (P less than 0.05) in [Cai] to above 50% of preischemic value after 30 min of ischemia. The [Cai] in the low [Cao] perfused group at 30 min of ischemia was 30% below the preischemic value. The peak of the [Cai] rise in the low [Cao] perfusate group was markedly attenuated and delayed to 40 min. Taken together it appears that low calcium perfusate (100 microM) prior to ischemia attenuates the ischemia-induced [Cai] rise, delays the onset, and decreases the force of contracture with irreversible ischemic injury.
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