G G Corbucci1. 1. Institute of Anaesthesia and Intensive Care, University of Cagliari.
Abstract
BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in human ischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos synthesis in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55 +/- 8 min ischemic period and the third 34 +/- 5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malondialdehyde (MDA) levels. In a small number of patients (N = 5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome oxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterizes peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincing that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.
BACKGROUND: Previous studies have shown that biomolecular and biochemical adaptive changes antagonize oxidative damage due to hypoxia and ischemia in myocardial cells. The aim of our study was to verify in humanischemic and reperfused cardiac tissue the relationship between mitochondrial enzyme activities and the activation of HSP70 and c-fos synthesis in the context of a cytoprotective mechanism. Nitric oxide (NO) modulating effects on mitochondrial respiratory chain enzyme activities in ischemic and reperfused tissue were investigated (preliminary report). METHODS: During elective coronary artery bypass grafting, in 30 consecutive patients ventricle samples were taken one before aortic clamping the second after 55 +/- 8 min ischemic period and the third 34 +/- 5 after final reperfusion. Coronary sinus blood samples were taken in parallel to assess free radical release measured by malondialdehyde (MDA) levels. In a small number of patients (N = 5) nitric oxide tissue levels were analyzed. RESULTS: When compared with normoxic tissue, a significant decrease in cytochrome oxidase (COX) and succinate Cyt-c reductase (SCR) activities in ischemic and reperfused samples were observed. The activation of HSP70-72 and c-fos transcription factor was evident in courses of ischemia and reperfusion. Blood MDA levels underline the concept that oxyradical generation characterizes peroxidative damage in reoxygenated myocardial tissue while adaptive changes which occur in ischemic cells seem to antagonize the oxyradical injury. CONCLUSIONS: In the course of heart surgery the myocardial cell seems to prevent ischemic damage activating some peculiar biomolecular and biochemical adaptive changes which permit the reversibility of the oxidative injury. In contrast it appears evident that massive and rapid reoxygenation of the cardiac tissue leads to peroxidative damage due to oxyradical generation. Nitric oxide seems to play a crucial role in cellular adaptation to ischemia even if further studies will be needed to elucidate these findings. From the data obtained in this work we cannot draw certain conclusions in terms of human cardiac cell adaptation to ischemia whereas it seems convincing that reoxygenation, as actually employed in clinical practice, compromises the integrity of the cells.