Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts

Vincent M. Figueredo, Rolf Brandes, Michael W. Weiner, Barry M. Massie, S. Albert Camacho

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

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 Langendorf-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 μmol/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.

Original languageEnglish (US)
Pages (from-to)1794-1802
Number of pages9
JournalJournal of Clinical Investigation
Volume90
Issue number5
DOIs
StatePublished - Nov 1992
Externally publishedYes

Keywords

  • Contractility
  • Energy metabolism
  • Inorganic phosphate
  • Ischemia
  • pH

ASJC Scopus subject areas

  • Medicine(all)

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