title: Energy-related metabolites during and after induced myocardial infarction with special emphasis on the reperfusion injury after extracorporeal circulation.
abstract: In the clinical setting great efforts have been made with contradictory results to operate upon acutely myocardial ischaemic patients. The reasons for the absence of clear-cut results are not well understood nor are they scientifically explored. To resolve this problem further, we attempted to design an experimental in vivo model to mimic acute myocardial ischaemia followed by extracorporeal circulation (ECC) and reperfusion. One of the main targets of our protocol was monitoring of myocardial energy metabolism by microdialysis (MCD) during the periods of coronary occlusion (60 min), hypothermic (30 degrees C) ECC and cardioplegia (45 min), followed by reperfusion with (30 min) and without (60 min) ECC. In eight anaesthetized, open-chest pigs, myocardial lactate, pyruvate, adenosine, taurine, inosine, hypoxanthine and guanosine were sampled with MCD in both ischaemic and non-ischaemic areas. Myocardial area at risk and infarct size were quantified with the modified topographical evaluation methods. The principal finding with this experimental setup was a biphasic release pattern of lactate, adenosine, taurine, inosine, hypoxanthine and guanosine from ischaemic myocardium. Lactate levels were equally high in reperfused ischaemic and non-ischaemic myocardial tissue. Pyruvate demonstrated consistently higher values in non-ischaemic myocardium throughout the experiment. A pattern was discernible, lactate being a marker of compromised cell energy metabolism, and taurine being a marker of disturbed cell integrity. Of special interest was the increased level of pyruvate in microdialysates of non-ischaemic myocardium as compared with its ischaemic counterpart. In conclusion, we found disturbances in energy metabolism and cell integrity not only in ischaemic but also in non-ischaemic tissue during reperfusion implying that non-ischaemic myocardium demonstrated an unexpected accumulation of lactate and pyruvate. These new findings could at least partly be explicatory to the increased risk of heart surgery in connection with acute myocardial infarction.
authors.affiliation: Department of Cardiothoracic Surgery, University Hospital, Uppsala, Sweden.
authors.forename: V
authors.initials: V
authors.lastname: Zemgulis
authors.forename: G
authors.initials: G
authors.lastname: Ronquist
authors.forename: T
authors.initials: T
authors.lastname: Bjerner
authors.forename: A
authors.initials: A
authors.lastname: Henze
authors.forename: A
authors.initials: A
authors.lastname: Waldenström
authors.forename: S
authors.initials: S
authors.lastname: Thelin
authors.forename: G
authors.initials: G
authors.lastname: Wikström
mesh_terms: D000241:Adenosine / Q000032:analysis; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015314:Dialysis Solutions / Q000737:chemistry; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005112:Extracorporeal Circulation; D006147:Guanine / Q000032:analysis; D006324:Heart Arrest, Induced; D019271:Hypoxanthine / Q000032:analysis; D007288:Inosine / Q000032:analysis; D019344:Lactic Acid / Q000032:analysis; D017551:Microdialysis; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D019289:Pyruvic Acid / Q000032:analysis; D015427:Reperfusion Injury / Q000378:metabolism*; D013552:Swine; D013654:Taurine / Q000032:analysis
chemical_list: D015314:Dialysis Solutions; D013654:Taurine; D019271:Hypoxanthine; D019344:Lactic Acid; D007288:Inosine; D006147:Guanine; D019289:Pyruvic Acid; D000241:Adenosine