[Significance of mitochondrial Ca2+ transport in ischemic injury and myocardial protection].
The role of calcium regarding the origin of irreversible impairment of the myocardial tissue is being intensively studied. An important role in this process is played by mitochondria which by means of the active Ca2+ uptake stimulate its oxidative metabolism and intervene into the Ca2+ homeostasis in mitochondrial cells. The study investigates the influence of cardioprotective substances with distinct mechanisms of the mitochondrial Ca2+ uptake effect. The experiments were performed on chinchilla buck rabbits of 2500-3000 g of body weight. Isolated hearts were perfused according to the method of Langendorff, ischemia was evoked by a 60-minute stoppage of the coronary blood flow. The cardioprotective substances were added into the perfusion solution prior to ischemia inducement. We investigated the following cardioprotective substances: Spirapril (ACE inhibitor), magnesium (Mg2+), and MDL 73,404 (antioxidant, synthetic analogue of alpha-tocopherol). After the 60-minute ischemy the mitochondrial Ca2+ uptake decreased by 43% in comparison with the control group (p < 0.01), Spirapril caused its accretion by 35% in comparison with the ischemic group (p < 0.05), and magnesium increased the uptake even by 52% (p < 0.001). The MDL 73,404 substance had no effect on the mitochondrial Ca2+ uptake. On the basis of experimental results we assume that the cardioprotective effects of Spirapril and magnesium can be besides other factors intermediated also by the increase of intramitochondrial enzymatic activity in consequence of augmented transport of Ca2+ into mitochondria. The cardioprotective effect of the MDL 73,404 substance is assumedly caused by its antioxidant properties. (Fig. 4, Ref. 21.)
Kucharská
J
J
Farmakobiochemické laboratórium III. internej kliniky LFUK v Bratislave, Slovakia.
Gvozdjáková
A
A
Herichová
I
I
Gvozdják
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D011817:Rabbits; D014810:Vitamin E / Q000031:analogs & derivatives / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; C067190:MDL 73404; D014810:Vitamin E; D004656:Enalapril; C052555:spirapril; D008274:Magnesium; D002118:Calcium
Význam transportu Ca2+ mitochondriami pri ischemickom poskodení a ochrane srdcového svalu.