Cardiac contractile dysfunction during mild coronary flow reductions is due to an altered calcium-pressure relationship in rat hearts.
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.
Figueredo
V M
VM
Department of Medicine (Cardiology), University of California, San Francisco 94143.
Brandes
R
R
Weiner
M W
MW
Massie
B M
BM
Camacho
S A
SA
D000818:Animals; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D003326:Coronary Circulation / Q000502:physiology*; D004734:Energy Metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D010710:Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D010710:Phosphates; D002118:Calcium