Energy-Related Metabolites during and after Induced Myocardial Ischemia and Retroperfusion of the Coronary Sinus : An Experimental Study in the Pig with the Microdialysis Technique and Extracorporeal Circulation

Sammanfattning: In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischemic patients. The reasons for the absence of unambiguous results are not well understood nor are they scientifically explored. An experimental model was designed to mimic acute myocardial ischemia followed by extracorporeal circulation and reperfusion. This was accomplished with and without retroperfusion of the coronary sinus (RCS) during the period of vascular occlusion. Myocardial energy-related metabolites were monitored in open-chest pigs by microdialysis. The relationships between adenosine, taurine and nucleoside transport inhibition in ischemic myocardium are highlighted separately.Myocardial area at risk and infarct size were quantified.The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischemic myocardium. Of special interest was the unexpected finding of increased level of pyruvate in microdialysates of also non-ischemic myocardium. We have observed a preferentially anaerobic energy metabolism in potentially ischemic myocardium during continuous and pulsatile RCS, despite the alleviated effect of RCS as regards infarct size limitation.We found disturbances in energy-metabolism (studies without RCS) most probably due to a compromised function of the pyruvate dehydrogenase complex not only in ischemic but also in non-ischemic tissue during reperfusion. Even in presence of oxygen (studies with RCS-assist) the pattern of an aerobic production of lactate was obvious. We conclude that prolonged (60 min) anaerobic energy metabolism does not pose an immediate threat to cell viability but could even sustain myocyte survival. The overall net result of our studies on taurine transport suggests that taurine may represent an energy store of myocytes. This should be understood as a chemical intracellular gradient of taurine as a result of already performed osmotic work. This energy store could be exploited for Ca2+ extrusion to counteract Ca2+ overload and should be regarded as an equivalent to the high energy store of phosphocreatine.

  Denna avhandling är EVENTUELLT nedladdningsbar som PDF. Kolla denna länk för att se om den går att ladda ner.