Limitation of experimental infarct size by levocarnitine chloride (LC-80), a new mitochondrial function-reactivating agent

Abstract

The effect of LC-80 on infarct size induced by 6 hr coronary occlusion was studied in anesthetized dogs. LC-80 at a dose of 100 mg/kg, i.v. was injected 5 min after coronary occlusion and then infused at a rate of 50 mg/kg, i.v./hr until the heart was excised. The two risk areas were determined both by injecting a fluorescent dye (Thioflavin S) into the left atrium (in vivo) and by perfusing the non-occluded coronary bed with Monastral Blue (in vitro). The infarct size was determined by topographically tracing the area of myocardium unstained by triphenyltetrazolium chloride. Four zones such as Zone 1 (normal tissue), Zone 2 (tissue characterized by collateral blood flow), Zone 3a (tissue developing necrosis), Zone 3b (necrotic tissue) were delimitated. As a result, (1) LC-80 significantly diminished the incidence of ventricular arrhythmias. (2) LC-80 significantly inhibited the decrease in myocardial free carnitine level in Zone 2 and Zone 3b. (3) LC-80 significantly reduced the infarct size expressed as a percentage of the risk area and increased the size of Zone 2. (4) In the electron microscopic findings, LC-80 showed lesser morphological changes such as swollen mitochondria and intracellular and extracellular edema, especially in Zone 2. (5) LC-80 may be useful for inhibiting the evolution of myocardial ischemic cell death both by the protection of ischemic myocardium and presumably by the increase in the collateral blood flow.