Ferrari R, Ceconi C, Cargnoni A, Pasini E, Boffa G M, Curello S, Visioli O
Cattedra di Cardiologia, Università di Brescia, Italy.
Cardiovasc Drugs Ther. 1991 Feb;5 Suppl 1:57-65. doi: 10.1007/BF00128244.
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.
为评估丙酰 -L-肉碱是否能保护兔心脏免受缺血和再灌注引起的损伤，将不同浓度含丙酰 -L-肉碱的培养基灌注到离体心脏中。在对照、常氧灌注、60分钟低流量缺血（37℃）随后30分钟再灌注期间，监测舒张期压力和收缩期压力；收集冠状动脉流出液并检测乳酸和肌酸磷酸激酶（CPK）；收获线粒体并检测氧化磷酸化和钙含量；检测组织中的三磷酸腺苷（ATP）和磷酸肌酸浓度。丙酰 -L-肉碱减轻了线粒体功能的缺血性损伤以及ATP组织储备的消耗。再灌注时，用丙酰 -L-肉碱处理的心脏在左心室功能、ATP和CP储备的补充以及线粒体功能方面比未处理的心脏恢复得更好。再灌注诱导的线粒体钙超载和CPK释放也减少。丙酰 -L-肉碱的作用呈剂量依赖性。在10^(-8)M时它未能改变缺血和再灌注损伤，但在10^(-7)M时能很好地起到保护作用。在10^(-6)M时未获得进一步的保护作用。因此，丙酰 -L-肉碱可保护心肌免受缺血和再灌注的一些有害影响。特别是它能保护线粒体功能，可能部分是通过防止线粒体钙超载实现的。由于这种保护作用在常氧期间不存在负性肌力作用或缺血期间不存在冠状动脉扩张作用的情况下发生，所以不能将其归因于能量节省作用或氧输送的改善。
