Metabolic intervention during blood cardioplegia. Clinical studies in coronary surgery and heart transplantation

Sammanfattning: Myocardial ischemia and injury (infarction) during open heart surgery and heart transplantation is a problem in spite of the fact that it is a safe procedure today. The myocardial substrate metabolism is well investigated before and after the cardioplegic period but little knowledge exists about the myocardial metabolic changes during cardioplegia. We hypothesized that the myocardial metabolic abnormalities and decreased oxygen extraction during cardioplegia may depend on restricted access of the intermediate a - ketoglutarate (a-KG) in the citrate cycle (Krebs). We also hypothesized that the during ischemic conditions persisting insulin resistance, could be bridged by addition of supra physiological doses of insulin. During heart transplantation the heart is exposed for greater trauma than under conventional heart surgery. Early graft failure and allograft injury is an obvious problem and potentially aggravating factors has been sparsely evaluated. The aim of this study was to investigate the effects of adding a-KG and insulin to blood cardioplegia on the myocardial extraction and substrate metabolism and to identify predictors in development of ischemic injury in heart transplantation.Seventy-four patients, 49 submitted for elective first-time coronary artery bypass grafting and 25 for heart transplantation, were included in three prospective, randomized and controlled studies. Two studies were performed during coronary artery bypass grafting and one during heart transplantation. In paper I and II we evaluated the effect on myocardial oxygen extraction and substrate metabolism after addition of a-KG to blood cardioplegia. GIK (glucose-insulin-potassium) was administrated in combination with a-KG in paper III. During heart transplantation GIK was administrated in similar way as in paper III and variables were detective in order to identify predictors causing ischemic injury on the allograft.Addition of a-KG to blood cardioplegia significant increased the myocardial oxygen extraction and significant reduced the release of the ischemic markers creatine kinase MB and troponin T compared to the control group. a-KG alone had no effect of myocardial substrate metabolism. Insulin (GIK) showed improvement on the myocardial substrate metabolism during cardioplegia compared to the control group. On the contrary addition of insulin had no effect on allograft substrate metabolism during implantation. The age of donor and the implantation time seemed to be predictors responsible for development of ischemic injury on the allograft.