Amiodarone Modulation of Intracellular Transport of Calcium Ions in Cardiomyocites

The influence of amiodarone on intracellular transport of calcium ion in cardiomyocytes of rat was investigated. The experiments were performed on isolated papillary muscles of Wistar rats. Force-frequency dependence (0.7, 1, 2, 3, 4 Hz), extrasystolic and postextrasystolic contractions and post-rest (4-60 s) reactions of rat myocardium after amiodarone treatment (1 μM) were investigated. Decay potentiation coefficient of contraction force was estimated. Results. The analyses of force-frequency dependence has shown that amiodarone prevent the decreasing of the force contraction at increasing of the stimulation frequency. Amiodarone promotes increase of the time constant t1(T50), that indicate the drug promotes acceleration of Са2+ transport inside the SR resulting increase of Са2+ in the places of its release from the sarcoplasmic reticulum (SR). Treatment of papillary muscle with amiodarone decreased amplitude of extrasystolic contractions. As known, postextrasystolic and post-rest reactions of myocardium characterize the SR function. We have found amiodarone increased potentiation of postextrasystolic and post-rest contractions. Preliminary caffeine perfusion of muscles preparations cancelled the amiodarone-induced increasing postextrasystolic and post-rest potentiation. However, potentiation decay coefficient before and after treatment with amiodarone didn’t have difference. Conclusions, amiodarone influences on intracellular calcium ions homeostasis by modulation SR functions related with most likely are stipulated either by activation of Са2+ transport from uptake sites to release sites or by prevent of Са2+ leakage from the SR.

Modulation of Interval–Force Dependence of Rat Papillary Muscle at Acute and Course Exposure of Amiodarone

Change of interval–force dependence of rat papillary muscles at acute and course use of amiodarone was investigated. Methods. The experiments were performed on isolated papillary muscles of Wistar rats. The extrasystolic (0,2-1,5 s), postextrasystolic contractions and post-rest (4-60 s) reactions of rat left papillary muscles perfused Krebs-Henseleit solution with amiodarone (1 μM) and papillary muscles of rat treated amiodarone in dose 20 mg/kg/day for 14 days were investigated. Results. It has been found that both acute and course use of amiodarone decreases the amplitude of extrasystolic contraction. At the same time, only acute use of amiodarone leads to additional enhancement of potentialtion of contractile response at extrasystolic impulse and performance of post-rest test. Conclusion was made, that both acute and course use of amiodarone decreases excitability of cardiomyocytes but only at course use this antiarrythmic drug increases effective refractory period of myocardium. Acute exposure of amiodarone is accompanied with change of functional state of cardiomyocyte sarcoplasmatic reticulum.

Age changes of antyoxidant system and free-radical processes in rats at formation of postinfarction cardiosclerosis

Estimation of age dependent changes of the lipid peroxidation (LPO) intensity, content of stable metabolites of nitrogen oxides (NO) and antioxidant enzyme activities in rat blood serum in conditions of experimental postinfarction cardiosclerosis (PICS) is carried out. Initiation of the postinfarction remodeling of animals has been carried out with coronary occlusion, definition of LPO and NO metabolites indices has been performed after 45 days. Investigations have been carried out on 40 four and twelve-month-old male Wistar rats with mass 200-250 gand 400 -450 g, accordingly. Statistical analysis of the results was performed using the Mann-Whitney-Wilcoxone criterion. It has been found that already intact animals have age specificity of indices under consideration. The expressed activity of LPO processes on the background of reduction of endogenous fermentative antioxidant (SOD and catalase) activity as well as nitrite concentration in blood serum is characteristic for PICS of 4-month-old animals. PICS of 12 month-old rats is accompanied with suppression of the LPO processes on the back- ground of reduction of the antioxidant enzyme intensity and increase of NO metabolites production. The following conclusions have been drawn. Process of ontogenesis is characterized by imbalance between pro-and antioxidant processes in rat blood. Increase in catalase activity and concentration of the TBC-active products at simultaneous decrease of SOD activity and content of diene conjugates has been noted. The organism of young animals responds with persistent increase of LPO processes and decrease of SOD and catalase activity on formation of postinfartion cardioslerosis. The less expressed increase of lipid peroxidation activation and decrease of catalase activity has been noted in the organism of old animals within 45 day after PICS formation.