Improvement of myocardial function after global hypoxia by protection of the inner mitochondrial membrane.
In the present study the hypothesis is tested that hypoxia causes morphological damage to the inner mitochondrial membrane and that this damage can be reversed by modification of the reoxygenated perfusate. Using the working rat heart model, hearts in group I (n = 40) were subjected to a 30 min normothermic, normoxic phase and a 90 min hypoxic phase, followed by 60 min reoxygenation. Hearts in group II (n = 32) were also subjected to a 30 min normoxic and a 90 min hypoxic phase. However, after 30 min of reoxygenation 1.5 mmol/l 2-mercaptopropionylglycine (MPG) was injected in the reoxygenated solution in order to test its ability to improve mitochondrial function. Mitochondrial function was assessed by measuring oxygen uptake (ST3), ST4, respiratory control index (RCI), ADP/O and oxidative phosphorylation rate (OPR). In addition mechanical function (heart rate, aortic and coronary flow, cardiac output, stroke volume) was monitored along with ultrastructural parameters. 90 min of hypoxia caused a deterioration of all parameters with persistent impairment in hemodynamic, morphologic and biochemical functions after 60 min of reoxygenation (group I). The role of the ATP-synthetases in the pathogenesis of oxygen-paradox is discussed. In contrast, the MPG-enriched reoxygenated solution (group II) improved hemodynamics, ultrastructure and mitochondrial function significantly (alpha = 0.05). It is concluded from these data that the ATP-synthetases are damaged during oxygen-deficiency and that MPG may be a useful drug for protecting the inner mitochondrial membranes during reoxygenation.
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000603:Amino Acids, Sulfur / Q000494:pharmacology*; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D000860:Hypoxia / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000187:drug effects*; D008297:Male; D008854:Microscopy, Electron; D008929:Mitochondria, Heart / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013318:Stroke Volume / Q000187:drug effects; D008625:Tiopronin / Q000494:pharmacology*
D000603:Amino Acids, Sulfur; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D008625:Tiopronin; D000251:Adenosine Triphosphatases