[Study of mithochondrial permeability transition pore in the development of myocardial and vascular contractility...

In experiments on the isolated myocardial and vascular preparations the role of the mithochondrial permiability transition pore (mPTP) in the development of reperfusion injury was investigated. Co-perfusion of the previously activated myocardial trabecula (MT) and arterial rings (AR) by solution collected during the first 5 min of isolated heart reperfusion, caused a sharp and significant decrease of tonic tension of both isolated preparations. Besides the significant inhibition of the MT and AR reactions after electrical stimulation, modulation of AR reaction by the influence of MT is also registered. The solution collected at first minutes of heart reperfusion, preserve a dilation property within 24 hours of storage at room temperature. Preliminary perfusion of MT and AR with methylen blue (MB, 10(-4) M/l) or the addition to the solution dithiothreitol (DTT, 2 x 10(-5) M/l) and diethyl maleate (DEM, 2 x 10(-5) M/l) resulted in an almost complete inhibition of this dilatation influence on the isolated preparations. The data received testify that the solution comprise a NO-containing substance, possible nitrosoglutation. Pre-incubation (2 min) MT in a solution with mPTP activator phenylarsine oxide (PAO, 10(-5) M/l) and subsequent reperfusion with a control solution resulted in deep and irreversible decrease of tonic tension and inhibition of contractility of both isolated preparations. The received data are qualitatively similar to results described above. Our data and results received in additional experiments on isolated mitochondria allow us to assert that solution flowing from the ischemized heart contains the stable mitochondrial factor (SMF) with a significant dilatation property. An addition of MB and DEM in the reperfusion solution abrogated its dilation influence. Co-perfusion (10 min) of the injured MT and AR by the solution with nitrosoglutation (10 (-5) M/l) restored normal contractility of the isolated preparations and modulation of the AR reaction by the influence of MT. It once again confirms the presence of an NO-containing substance in the SMF content. Thus, the mPTP activation plays the key role in the development ofmyocardial reperfusion injury and results in release of SMF, which can be the basic agent of paracrine regulation of myocardial contractility, coronary and peripheral vessels tone.