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Effect of Diabetes on Outcome after Cardiac Arrest and Cardiopulmonary Resuscitation with Postconditioning Strategies in a Rodent Model

Subject Area Anaesthesiology
Term from 2018 to 2020
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 397561247
 
Final Report Year 2020

Final Report Abstract

Despite advanced treatments in cardiopulmonary resuscitation (CPR) and enhanced research, survival in a good neurologic condition from out-of-hospital cardiac (OHCA) arrest is still less than 10% and has plateaued since 2012. Especially, patients with metabolic syndrome and Type 2 Diabetes Mellitus (T2DM) do not only have a higher risk for cardiac arrest, but also have a decreased chance of survival. Since existing research models rarely take comorbidities into account, the overall goal of my postdoctoral research grant was to establish a new and more relevant research model of cardiac arrest and cardiopulmonary resuscitation in a rodent model with comorbidities. By using Zucker Diabetic Fatty (ZDF) rats, we wanted to evaluate the effect of metabolic syndrome and T2DM on outcome in an animal model with the potential to test new and promising therapies. We hypothesized that T2DM is associated with a lower chance for return of spontaneous circulation (ROSC) and/or a worse outcome regarding heart function after asphyxial CA compared to their lean littermates. Conversely, there was no difference in ROSC rates and the diabetic ZDF rats showed a significantly higher blood pressure related to an increased EF%. In addition Troponin levels were lower in diabetic rats, while neurologic damage marker such as NSE were lower in non-diabetic animals. The improved cardiac function in diabetic rats after cardiac arrest, limited the options to test therapies, but set the base for further examinations exvivo. Another unexpected effect of T2DM was seen in Langendorff-isolated hearts of Zucker Spontaneous Hypertensive (ZSF-1) rats. We were able to show for the first time that adjusting buffer glucose levels to higher levels as seen in the same rat in-vivo, did not worsen the myocardial function in isolated Langendorff-hearts. Therefore, we were not able to conclude that T2DM might have a worsened effect on ischemia-reperfusion injury in experimental models. Overall we were able to work on important steps for the development of new relevant research models.

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