Techniques to improve neurological outcome after cardiac surgery

Cardiac surgery procedures, such as coronary bypass and valvular operations, usually require taking over circulation by a heart-lung machine (cardiopulmonary bypass or CPB). The aim of this thesis was to improve the postoperative outcome of cardiac surgery by examining different therapeutic interventions. In patients undergoing bypass surgery, randomized to undergo surgery with or without the use of CPB, we investigated the effect of tissue oxygenation on functional outcome. Postoperative cognitive dysfunction (POCD) occurred more often in the CPB-group, but was not associated with alterations in intraoperative brain tissue oxygenation. To understand POCD, we investigated the role of surgery on the brain inflammatory response in aged mice. Major surgery itself does not provoke exaggerated neuroinflammation, making it unlikely to associate with POCD. Finally, we explored the optimal cooling (hypothermia) strategy during cardiac surgery. In a cohort of more than 8,000 patients, we established that a core body temperature of 33oC is associated with best survival. Moreover, we could discriminate between patients who could be easily cooled and those who resisted cooling, the latter established higher postoperative survival. Further, we explored the influence of deep cooling on brain inflammation in a rat CPB model. Here, deep hypothermia (18oC) provoked increased neuroinflammation in vulnerable brain regions and lower production of neuroprotective cold shock proteins, compared to mild hypothermia (33oC). Together, these data indicate that neuroinflammation is an uncommon consequence of surgery, unless it is combined with deep hypothermia. Consequently, provoking mild hypothermia during cardiac surgery seems a recommendable strategy to protect the brain.