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Published on: April 13, 2015
Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure
V M Figueredo1, R Brandes, M W Weiner
1Department of Medicine (Cardiology), University of California, San Francisco 94143.
Insights
Mild coronary flow reduction depresses heart contractility through an altered calcium-pressure relationship, not decreased calcium. Increased inorganic phosphate (Pi) and lower vascular pressure contribute to this effect.
Area of Science:
- Cardiovascular Physiology
- Myocardial Metabolism
- Biophysics
Background:
- Coronary artery stenosis reduces blood flow, causing myocardial contractile depression.
- Mechanisms of contractile depression during mild flow reduction are unclear, unlike severe reductions.
- Previous studies show conflicting results on cytosolic free calcium (Cai) and inorganic phosphate (Pi) levels.
Purpose of the Study:
- To investigate the roles of Cai, Pi, pH, and vascular pressure in contractile depression during mild coronary flow reduction.
- To differentiate between Cai reduction and altered calcium-pressure interactions as mediators.
Main Methods:
- Langendorff-perfused rat hearts.
- Indo-1 calcium fluorescence for Cai measurements.
- 31P magnetic resonance spectroscopy for Pi and pH analysis.
Main Results:
- Cai and diastolic calcium levels remained unchanged during flow reductions up to 50%.
- Pi significantly increased with a 25% flow reduction, correlating with developed pressure.
- pH was stable until 50% flow reduction; superphysiological vascular pressure increased contractility without altering Cai.
Conclusions:
- Mild coronary flow reduction depresses contractility via an altered calcium-pressure relationship, not decreased Cai.
- Increased Pi and decreased intravascular pressure may mediate this altered relationship.
- Findings challenge the direct role of Cai reduction in mild flow-reduction-induced contractile dysfunction.
Abstract:
Coronary artery stenosis or occlusion results in reduced coronary flow and myocardial contractile depression. At severe flow reductions, increased inorganic phosphate (Pi) and intracellular acidosis clearly play a role in contractile depression. However, during milder flow reductions the mechanism(s) underlying contractile depression are less clear. Previous perfused heart studies demonstrated no change of Pi or pH during mild flow reductions, suggesting that changes of intravascular pressure (garden hose effect) may be the mediator of this contractile depression. Others have reported conflicting results regarding another possible mediator of contractility, the cytosolic free calcium (Cai). To examine the respective roles of Cai, Pi, pH, and vascular pressure in regulating contractility during mild flow reductions, Indo-1 calcium fluorescence and 31P magnetic resonance spectroscopy measurements were performed on Langendorff-perfused rat hearts. Cai and diastolic calcium levels did not change during flow reductions to 50% of control. Pi demonstrated a close relationship with developed pressure and significantly increased from 2.5 +/- 0.3 to 4.2 +/- 0.4 mumol/g dry weight during a 25% flow reduction. pH was unchanged until a 50% flow reduction. Increasing vascular pressure to superphysiological levels resulted in further increases of developed pressure, with no change in Cai. These findings are consistent with the hypothesis that during mild coronary flow reductions, contractile depression is mediated by an altered relationship between Cai and pressure, rather than by decreased Cai. Furthermore, increased Pi and decreased intravascular pressure may be responsible for this altered calcium-pressure relationship during mild coronary flow reductions.
