[Role of nitric oxide and mitochondrial permeability pore in changes of oxygen consumption in the working skeletal muscle]. / Rol' oksydu azotu ta mitokhondrial'noï pory v zmini kysnevykh rezhymiv pratsiuiuchoho skeletnoho m'iaza.

On anaesthetized dogs the role NO and mitochondrial permeability transition pore (MPTP) in the regulation of regional blood circulation, efficiency of oxygen using, and muscle contraction force was investigated. Under different frequency stimulation it was shown, that short-term (30") smoothly tetanic contraction (40 Hz) is more economic for a skeletal muscle than short-term (30") single contractions (8 Hz) with respect to the efficiency of oxygen using. Injection NOS inhibitor L-NMMA (2.7 mg/kg, i.a.) resulted in pronounced fall of a functional hyperemia magnitude (P < 0.01), significant reduction of the muscle contractions force (P < 0.01), and efficiency of oxygen using (P < 0.01), in m.gastrocnemicus, in comparison with control. Pretreatment with an exogenous activator of MPTP phenilarsine oxide (PAO, 0.2 mg/kg, i.a.) caused a marked inhibition of an endothelium-dependent vessels dilation on skin-muscle region of rear limb. At the same time the muscle contractions force was significantly decreased (P < 0.01) and efficiency of oxygen using was diminished too (P < 0.01). This was accompanied by an appearance in blood from v. femoralis mitochondrial factor (MF), indicating MPTP activation. Preliminary injection of the exogenous NO donor sodium nitroprusside (0.2 mg/kg, i.v.) prevented considerably an inhibition of a dilation vessels reserve, a fall of muscle contractions force (P < 0.01) and considerably reduced oxygen cost (P < 0.01) of a m.gastercnemicus work also. The concentration of MF in blood from v. femoralis also was considerably reduced (P < 0.001) that has been the evidence of MPTP inhibition. Thus, activation of MPTP and development of oxidative stress resulted in endothelium dysfunction, a force of muscle contraction diminishing and a significant decrease in efficiency of oxygen using. NO essentially reduced the negative effects of MPTP activation and was antagonist of oxidative damages development.

[Determination of the stable mitochondrial factor in vivo]. / Vyznachennia stabil'noho faktora mitokhondrial'noho pokhodzhennia in vivo.

We have determined a release of a stable mitochondrial factor (SMF) into the outflowing blood in vivo. That effect was induced by ischemia/reperfusion or phenylarsin oxide (PAO)--the activators of the mitochondrial permeability transition pore (MPTP) and the oxidative stress. The SMF was measured by a spectrophotometer in the range of wave-lengths 230-260 nm with the absorption maximum of 240-250 nm. The SMF release was accompanied with a decrease in the myocardial contractility, disturbances in cardiodynamics and regional blood circulation. The data obtained have demonstrated that the SMF can be used as a marker of MPTP opening in vivo.

[Factor released during myocardial ischemia reperfusion may become a marker of opening of the mitochondrial permeability transition pore]. / Faktor, iakyi vyvil'niuiet'sia pid chas reperfuziï ishemizovanoho sertsia, mozhe buty markerom vidkryttia mitokhondrial'noï pory.

In experiments on isolated hearts of guinea-pigs, on a model of ischemia-reperfusion cardiac reperfusion has been shown to result in a constriction of coronary vessels, arrhythmia, an inhibition of the contractile activity of the myocardium, and an increase in an oxygen cost of the myocardial work. Apart from that, a stable agent was detected in a reperfusion solution by spectrophotometry on the wave length of 250 nM. Similar deterioration of the heart function and the availability of the stable agent in the solution were observed under influence of the known activators of mitochondrial permeability transition pore-phenilarsine oxide and antimycin A. In anaesthetized animals a release of the stable factor into the blood was induced by either ischemia-reperfusion or those activators. Application of the known inhibitors of the mitochondrial permeability transition pore cyclosporin A or trolox (water-soluble vitamin E) decreased remarkably both the cardiodynamic deterioration and a release of the stable factor under heart reperfusion. Mitochondrial origin of the factor was confirmed in experiments on isolated mitochondria. Thus, the detected factor has been determined to be released from mitochondria at the opening of mitochondrial permeability transition pore and is thought to be the marker of its opening in experiments in vitro and in vivo.

[Study of a factor released during myocardial ischemia reperfusion and its effects on myocardial, coronary and peripheral vessels]. / Faktor, iakyi vyvil'niuiet'sia pid chas reperfuziï ishemizovanoho sertsia, doslidzhennia vplyvu na miokard, koronarni ta peryferychni sudyny.

The effect of reoxygenated coronary effluent of an isolated guinea-pig heart on a sequentially perfused second heart, right auricle trabecula and arterial vessel rings was studied after 20 min ischaemia of the first heart. It has been shown that a factor released after myocardial ischemia/reperfusion stimulates arrhythmia, decreases myocardial contractility of the second heart and depresses tonical tension of the right auricle trabecula and arterial vessel rings. Storage of the coronary effluent up to 24 h did not modify its effects. These results suggest stable factor released from an isolated heart after ischaemia at reperfusion to exert humoral effect not only on a myocardial contractility and coronary circulation but on the peripheral vessels tonus.

[Protection of the heart from reperfusion injury and ineffective oxygen using inhibitors of the mitochondrial permeability transitional pore]. / Poperedzhennia postreperfuziinykh porushen' funktsïi sertsia ta neefektyvnoho vykorystannia kysniu za dopomohoiu inhibitoriv vidkryttia mitokhondrial'noï pory.

UNLABELLED: In experiments on isolated hearts of guinea-pig, perfused under Langendorff preparation, possible protection of hearts from reperfusion injury by the known inhibitors of mitochondrial permeability transition pore--cyclosporin A, and trolox--water-soluble vitamin E was studied. It has been shown that cardiac reperfusion was followed with an increase in an oxygen cost of myocardial work (by 83% from control level in 40 min of reperfusion), in addition to the disturbances of cardiac contractility, tone of the coronary vessels and heart rate. The heart function and myocardial oxygen metabolism disturbances, due to global 20 min ischaemia and reperfusion, were essentially decreased by a preliminary application of investigated agents. Trolox improved cardiac recovery both when it was perfused in vitro and after its administration per os. In 40 min of heart reperfusion LVdeveloped pressure was 79% as compared to 51% in that at control; dP/dtmax and dP/dtmin were 88% and 85% accordingly against 66% and 45% in control; oxygen cost of myocardial work didn't change reliably). CONCLUSION: Postreperfusion disturbances of cardiac contractility, tone of the coronary vessels and heart rate, as well as noneffective oxygen utilization by the heart tissue were due to an opening of mitochondrial permeability transition pore.