The effect of propionyl-L-carnitine on the ischemic and reperfused intact myocardium and on their derived mitochondria.
To assess whether propionyl-L-carnitine protects rabbit heart against the deterioration caused by ischemia and reperfusion, isolated hearts were infused with a medium containing it in different concentrations. During control, normoxic perfusion, and 60 minutes of low-flow ischemia (37 degrees C) followed by 30 minutes of reperfusion, diastolic, and developed pressures were monitored; coronary effluent was collected and assayed for lactate and creatine phosphokinase (CPK); mitochondria were harvested and assayed for oxidative phosphorylation and calcium content; and tissues for concentration of adenosine triphosphate (ATP) and creatine phosphate. Propionyl-L-carnitine reduced the ischemic deterioration of mitochondrial function and the depletion of tissue stores of ATP. On reperfusion, hearts treated with it recovered better than the untreated hearts with respect to left ventricular performance, replenishment of ATP and CP stores, and mitochondrial function. The reperfusion-induced mitochondrial calcium overload and release of CPK were also reduced. The effect of propionyl-L-carnitine was dose dependent. At 10(-8) M it failed to modify ischemic and reperfusion damage but protected well at 10(-7) M. No further protection was obtained at 10(-6) M. Propionyl-L-carnitine thus protects the myocardium against some of the deleterious effects of ischemia and reperfusion. In particular it protects mitochondrial function, perhaps partly by preventing mitochondrial calcium overload. Because this protection occurs in the absence of a negative inotropic effect during normoxia or of a coronary dilatatory effect during ischemia, it cannot be attributed to an energy-sparing effect or to the improvement of oxygen delivery.
Ferrari
R
R
Cattedra di Cardiologia, Università di Brescia, Italy.
Ceconi
C
C
Cargnoni
A
A
Pasini
E
E
Boffa
G M
GM
Curello
S
S
Visioli
O
O
D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D002331:Carnitine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy*; D006321:Heart / Q000187:drug effects; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D011817:Rabbits
C003223:propionylcarnitine; D000255:Adenosine Triphosphate; D002331:Carnitine