Myocardial ischemia-reperfusion and cardioprotection. A study with microdialysis in a porcine model

Sammanfattning: The studies in this thesis are based on questions raised in the clinical setting. Perioperative myocardial ischemia occurs more often than recognized. This may lead to myocardial infarction, increased morbidity, mortality, and health care costs. In the first study, myocardial metabolism was investigated before, during, and after 30 min of regional coronary artery occlusion, utilizing the microdialysis technique, concomitantly with the monitoring of global circulation and local coronary artery flow in an open chest pig model. Myocardial interstitial metabolites demonstrated characteristic, significant, and reproducible changes as decreased glucose, increased glycerol, and increased lactate/pyruvate ratio during ischemia, normalizing after reperfusion. Of special interest was found that myocardial glycerol concentrations remained high initially at reperfusion, raising the hypothesis of this release corresponding to reperfusion injury. This model was used for the next two studies. In cardiac surgery, episodes of myocardial ischemia or decreased myocardial performance are highly expected to occur. Patients with poor cardiac function will have a double benefit of an inotropic drug with anti-ischemic properties. Levosimendan may have this potential. In the second study, it was demonstrated that an infusion of levosimendan started before the coronary artery occlusion, as compared to start during the ischemia, reduced the effect of ischemia on the myocardial metabolism, improved, and preserved cardiac performance during this period. In recent years, concerns with the use of perioperative beta-blockers have been debated. Beta-blockers may inhibit the pharmacological preconditioning elicited by volatile anaesthetics. In the third study, it was demonstrated that levosimendan, in the presence of beta-blockade, was still able to induce a cardioprotective effect on the myocardial ischemic metabolism. During cold cardioplegic storage, or in the future during preservation of donor hearts by perfusion, monitoring of the donor heart before transplantation may be of benefit. We hypothesized, that myocardial microdialysate glycerol will reflect progressive damage. As the first step in pursuing this, in the fourth study, the course of myocardial metabolites was investigated during ten hours of cold cardioplegic storage. An accelerating myocardial glycerol accumulation was demonstrated during storage, after an initial stable period, probably reflecting the acceptable storage time.