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Published on: June 15, 2020
Lack of direct role for calcium in ischemic diastolic dysfunction in isolated hearts
F R Eberli1, H Strömer, M A Ferrell
1Cardiac Muscle Research Laboratory, Boston University School of Medicine, Boston, MA, USA.
Insights
Ischemic diastolic dysfunction is not directly caused by changes in intracellular calcium levels. Experiments altering calcium availability during ischemia did not affect left ventricular diastolic pressure.
Area of Science:
- Cardiovascular Physiology
- Myocardial Ischemia Research
- Calcium Signaling in Heart Muscle
Background:
- Ischemia leads to increased intracellular calcium and diastolic dysfunction.
- The direct role of myocyte calcium levels in ischemic diastolic dysfunction requires clarification.
Purpose of the Study:
- To investigate if intracellular calcium levels directly determine diastolic dysfunction during ischemia.
Main Methods:
- Isolated rat and rabbit hearts were subjected to low-flow ischemia.
- Extracellular calcium levels were manipulated, and intracellular calcium was measured using aequorin.
- Left ventricular pressures were monitored throughout the experiments.
Main Results:
- Low-flow ischemia increased diastolic intracellular calcium by 270% and slowed calcium transient decline.
- Experimental increases in extracellular calcium doubled intracellular calcium but did not worsen ischemic diastolic pressure.
- Altering calcium availability during ischemia did not impact left ventricular diastolic pressure.
Conclusions:
- Ischemic diastolic dysfunction is not directly mediated by calcium-activated tension.
- Myocyte calcium levels may not be the primary driver of diastolic dysfunction during ischemia.
Background:
Ischemia is characterized by an increase in intracellular calcium and occurrence of diastolic dysfunction. We investigated whether the myocyte calcium level is an important direct determinant of ischemic diastolic dysfunction.
Methods And Results:
We exposed isolated, perfused isovolumic (balloon in left ventricle) rat and rabbit hearts to low-flow ischemia and increased extracellular calcium (from 1.5 to 16 mmol/L) for brief periods. Intracellular calcium was measured by aequorin. Low-flow ischemia resulted in a 270% increase (P:<0.05) in diastolic intracellular calcium, a 50% (P:<0.05) calcium transient amplitude decrease, and a 52% (P:<0.05) slowing of calcium transient decline. Diastolic pressure increased by 6+/-2 mm Hg (P:<0.05), and rate of systolic pressure decay decreased by 65% (P:<0.05). Experimentally increasing extracellular calcium doubled both intracellular diastolic calcium and calcium transient amplitude, concomitant with a developed pressure increase; however, there was no increase in ischemic diastolic pressure, slowing of the calcium transient decay, or further slowing of systolic pressure decay. Similarly, after 45 minutes of low-flow ischemia, after diastolic pressure had increased from 8.5+/-0.6 to 19.7+/-3.5 mm Hg (P:<0.001), intracoronary high-molar calcium chloride infusion increased systolic pressure from 36+/-4 to 63+/-11 mm Hg (P:<0.001), indicating an increase in intracellular calcium, but it decreased diastolic pressure from 19. 7+/-3.5 to 17.5+/-3.7 mm Hg (P:<0.01). Conversely, EGTA infusion decreased systolic pressure, indicating a decrease in intracellular calcium, but did not decrease diastolic pressure.
Conclusions:
When calcium availability was experimentally altered during ischemia, there was no alteration in left ventricular diastolic pressure, suggesting that ischemic diastolic dysfunction is not directly mediated by a calcium activated tension.
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