ABSTRACT
The parameters of coupled respiration and transport of calcium ions in mitochondria isolated from the heart of rats were studied in two modes of exposure to epinephrine for modelling myocardial damage. In 24 h after injection of 1.5 mg/kg epinephrine to rats, we observed a decrease in the efficiency of oxidative phosphorylation in heart mitochondria in the presence of both NADH- and FADH-dependent respiratory substrates. Increasing the epinephrine dose and exposure (2 mg/kg, 72 h) led to a more pronounced decrease in the ADP/O coefficient when succinate was used as a substrate, which indicated a predominant decrease in the activity of complex II of the respiratory chain. The injection of epinephrine in the two modes resulted in a decrease in the rate of calcium entry in rat heart mitochondria, but had no effect on mitochondrial calcium retention capacity, which reflects the resistance of the organelles to the induction of the Са2+-dependent pore. These findings suggest that both cardiomyopathy models in rats can be used to study the effectiveness of pharmacological therapy using mitochondria-targeted agents.
Subject(s)
Cardiomyopathies/metabolism , Electron Transport Complex II/drug effects , Mitochondria, Heart/drug effects , Myocardium/metabolism , Oxidative Phosphorylation/drug effects , Adenosine Triphosphate/biosynthesis , Animals , Calcium/metabolism , Cardiomyopathies/chemically induced , Cardiomyopathies/pathology , Cations, Divalent , Disease Models, Animal , Electron Transport Complex II/metabolism , Epinephrine/administration & dosage , Glutamic Acid/metabolism , Malates/metabolism , Male , Mitochondria, Heart/metabolism , Myocardium/pathology , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , NAD/metabolism , Rats , Rats, Wistar , Succinic Acid/metabolismABSTRACT
One hundred and seventeen patients with active sarcoidosis of the respiratory organs were treated according to 4 therapy regimens based on the use of corticosteroid drugs. Intermittent use of the corticosteroids was shown to be the most efficient (in 98.5 per cent). It allowed to lower the course dose by 25-30 per cent and to reduce the frequency of complications to 1.5 per cent. Inspite of high efficacy of kenalog 40, its use was limited because of adverse reactions in 19.2 per cent of the patients. It was difficult to eliminate the adverse reactions because of the drug prolonged action. The use of presocyl provided improvement in 62 per cent of the patients having contraindications for corticosteroid therapy. Patients with marked pneumosclerotic lesions should be treated with simultaneous use of corticosteroids and azathioprine.
