Ruthenium red improves postischemic contractile function in isolated rat hearts.
The effect of ruthenium red (inhibitor of mitochondrial calcium entry) on reperfusion contractile function and enzyme release was determined in isolated perfused rat hearts and compared with that of diltiazem. The hearts were made ischemic for 25 min and reperfused for 30 min. They were pretreated with 1-10 microM ruthenium red, 1 microM diltiazem, or vehicle. All concentrations of ruthenium red significantly improved reperfusion contractile function without affecting lactate dehydrogenase (LDH) release or contracture. Diltiazem significantly improved reperfusion function and reduced LDH release and contracture formation. Ruthenium red still improved function even when given only during reperfusion. Diltiazem increased reperfusion oxygen consumption and efficiency of oxygen utilization whereas ruthenium red improved efficiency without an increase in oxygen consumption. Diltiazem significantly increased reperfusion functional reserve in these hearts, although ruthenium red did not. Ruthenium red reduced coronary flow and contractile function in nonischemic myocardial tissue and the reduced function appeared to be secondary to the reduced coronary flow as well as to a direct negative inotropic effect. Thus, ruthenium red improved reperfusion contractile function and oxygen efficiency; this may be related to its ability to block mitochondrial calcium uptake.
Grover
G J
GJ
Department of Pharmacology, Squibb Institute for Medical Research, Princeton, New Jersey.
Dzwonczyk
S
S
Sleph
P G
PG
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003327:Coronary Disease / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D066298:In Vitro Techniques; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012430:Ruthenium Red / Q000494:pharmacology*
D012430:Ruthenium Red; D007770:L-Lactate Dehydrogenase; D004110:Diltiazem; D002118:Calcium