Emergency preservation and resuscitation

Sudden cardiac arrest is a major unresolved public health problem with an incidence of 96/100.000/year, and a survival rate of less than 10% if resuscitation is attempted. Mild hypothermia is so far the only clinically effective treatment against reperfusion injury caused by cardiac arrest. We hypothesize that brain protection by hypothermia could be more effective, if hypothermia was combined with invasive resuscitation strategies - EPR and E-CPR. EPR (emergency preservation and resuscitation) is the induction of a preservative state during cardiac arrest by means of deep hypothermia. E-CPR (extracorporeal cardiopulmonary resuscitation) is resuscitation with cardiopulmonary bypass. Complemented by EPR as a preservative strategy, E-CPR allows for goal-directed tissue perfusion, targeted temperature management, and controlled reperfusion with reperfusates that exert therapeutic properties. A preservative state for EPR is achieved by the immediate induction of deep hypothermia with the purpose of both a) applying a therapy for the reperfusion injury, and b) providing protection against ongoing deleterious processes after restoration of spontaneous circulation - ROSC (shock, no-reflow-phenomenon of the brain). We have developed a rat model of ventricular fibrillation cardiac arrest and resuscitation with conventional methods and E-CPR. In this model, we will establish neuro-behavioural testing methods, and systematically explore the potentials of various degrees of hypothermia and invasive resuscitation after prolonged cardiac arrest.

We developed and compared different techniques for resuscitation from ventricular fibrillation cardidac arrest, namely conventional CPR (cardiopulmonary resuscitation), and extracorporeal life support (ECLS) with heart-lung-machine, which also allows for rapid induction of therapeutic hypothermia to protect the brain during and after cardiac arrest.Furthermore we established novel techniques like brain microdialysis to monitor inflammatory and metabolic processe in the brain during cardiac arrest, resuscitation and after restoration of spontaneous circulation.Finally we established and refined methods to evaluate the outcome after cardiac arrest, like brain histology, neurological and behavioural tests including learing studies to define slight neurocognitive damage cause by cardiac arrest in seemingly normal animals.We found that up to 10 min of cardiac arrest, the technique of resuscitation, CPR or ECLS, is not of great importance for the outcome, whereas after 10 min of cardiac arrest, conventional CPR fails to generate long time survivors, and ECLS allows survival with good neurologic recovery in most animals. ECLS causes better cerebral perfusion pressures during resuscitation and more stable hemodynamics after restoration of spontaneous circulation, despite being more invasive.We tested, which temperature allows for best outcome, mild, deep hypothermia or normothermia, when ECLS is used, and found that mild hypothermia as used clinically is superior to the other groups. This gives support to current guidelines, that recommend the use of mild hypothermia after cardiac arrest. Our hypothesis that deeper degrees of hypothermia yield additional benefit for the brain, while the extracorporeal circulation protects the heart from detrimental cold effects, had to be rejected.An important part of our studies dealt with the establishment and validation of novel outcome parameters after cardiac arrest, because simple neurologic scores are rather crude tools to evaluate outcome. We were the first to successfully use brain microdialysis in this context, and evaluated the morris water maze as part of a neurocognitive testing battery. Brain microdialysis allows real-time measurement of lactate, pyruvate and glucose and other metabolic and inflammatory parameteres. The morris water maze demonstrated that cardiac arrest causes deficits in long term memory in our experiments.