Improvement of long-term preservation of the isolated arrested rat heart by trimetazidine: effects on the energy state and mitochondrial function.
Rat hearts, arrested in situ after intracaval injection of a cardioplegic solution, were preserved for 15 hours at 4 degrees C either by simple immersion or by low-flow (0.3 mL/min) perfusion. After preservation under both conditions, the left ventricular pressure developed by the reperfused hearts reached 8% and 43% of the control value (80 mm Hg), respectively. The addition of trimetazidine (TMZ; 10(-6) M) to the cardioplegic solution induced an improvement in functional recovery (by 2.4 and 1.5, respectively). This effect of TMZ was accompanied by a better energy profile illustrated by a 2-fold increase in the adenosine triphosphate to inorganic phosphate ratio and a reduction of intracellular acidosis as determined by 31P nuclear magnetic resonance spectroscopy. The function of the mitochondria (state 3, reduced nicotinamide-adenine dinucleotide [NADH] formation) isolated from the preserved hearts was significantly depressed in the stored hearts. The addition of TMZ to the cardioplegic solution partially protected oxoglutarate (and succinate) mitochondrial respiration and induced an increase in Ca2+ triggered NADH formation. These results show that the bioenergy status of the myocardial cell in isolated arrested stored rat heart is improved by the presence of TMZ in the preservation solution. Moreover, the experiments demonstrate that this effect includes protection of mitochondrial function and suggest that the drug could exert some control in the Ca2+ regulation of mitochondria.
Kay
L
L
Laboratoire de Physiologie Cellularie Cardiaque, Université Joseph Fourier, Grenoble, France.
Finelli
C
C
Aussedat
J
J
Guarnieri
C
C
Rossi
A
A
D000704:Analysis of Variance; D000818:Animals; D006003:Glycogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D014292:Trimetazidine / Q000494:pharmacology*
D007773:Lactates; D019344:Lactic Acid; D006003:Glycogen; D014292:Trimetazidine