Microdialysis Assessment of Cerebral Perfusion during Cardiac Arrest, Extracorporeal Life Support and Cardiopulmonary Resuscitation in Rats – A Pilot Trial

<div><p>Cerebral metabolic alterations during cardiac arrest, cardiopulmonary resuscitation (CPR) and extracorporeal cardiopulmonary life support (ECLS) are poorly explored. Markers are needed for a more personalized resuscitation and post—resuscitation care. Aim of this study was to investigate early metabolic changes in the hippocampal CA1 region during ventricular fibrillation cardiac arrest (VF-CA) and ECLS versus conventional CPR. Male Sprague-Dawley rats (350g) underwent 8min untreated VF-CA followed by ECLS (n = 8; bloodflow 100ml/kg), mechanical CPR (n = 18; 200/min) until return of spontaneous circulation (ROSC). Shams (n = 2) were included. Glucose, glutamate and lactate/pyruvate ratio were compared between treatment groups and animals with and without ROSC. Ten animals (39%) achieved ROSC (ECLS 5/8 vs. CPR 5/18; OR 4,3;CI:0.7–25;p = 0.189). During VF-CA central nervous glucose decreased (0.32±0.1mmol/l to 0.04±0.01mmol/l; p<0.001) and showed a significant rise (0.53±0.1;p<0.001) after resuscitation. Lactate/pyruvate (L/P) ratio showed a 5fold increase (31 to 164; p<0.001; maximum 8min post ROSC). Glutamate showed a 3.5-fold increase to (2.06±1.5 to 7.12±5.1μmol/L; p<0.001) after CA. All parameters normalized after ROSC with no significant differences between ECLS and CPR. Metabolic changes during ischemia and resuscitation can be displayed by cerebral microdialysis in our VF-CA CPR and ECLS rat model. We found similar microdialysate concentrations and patterns of normalization in both resuscitation methods used.</p><p><b><i>Institutional Protocol Number</i>:</b> GZ0064.11/3b/2011</p></div

CA1 lactate/pyruvate ratio against time.

<p>x-axis: Point of measurement, measurements 8min apart (sampling interval of 8min); y axis: Lactate/pyruvate ratios (mean values and standard deviation); CA, cardiac arrest; CPR, cardiopulmonary resuscitation; ECLS, extracorporeal cardiopulmonary life support; BL, baseline; ROSC, return of spontaneous circulation.</p

CA1 glucose mmol/l against time.

<p>x-axis: Point of measurement, measurements 8min apart (sampling interval of 8min); y axis: Glucose (mmol/l; mean values and standard deviation); CA, cardiac arrest; CPR, cardiopulmonary resuscitation; ECLS, extracorporeal cardiopulmonary life support; BL, baseline; ROSC, return of spontaneous circulation.</p

Mean arterial blood pressure in mm Mercury against time.

<p>X-axis: time in minutes; Y-axis: mean arterial blood pressure invasively measured in mmHg (mean with standard deviation); VFCA, ventricular fibrillation cardiac arrest; ROSC, return of spontaneous circulation; ECLS, extracorporeal life support; CPR, cardiopulmonary resuscitation; The p value displayed results from comparison of mean values the interval of measurements min 70 to 74.</p

Representative pictures of cerebral cortex, hippocampal CA1 region and thalamic reticular nucleus.

<p>A-C: Cerebral cortex without lesions in sham (A), CPR (B) and ECLS (C) animals; H&E staining, bar = 40μm; D-F: Hippocampal CA1 region without lesions in sham (D), CPR (E) and ECLS (F) animals; H&E staining, bar = 40μm; G-I: Thalamic reticular nucleus, no lesions in sham animal (G), numerous shrunken neurons with condensation of nuclear chromatin in CPR (H) and ECLS (I) animals; H&E staining, bar = 40μm; inserts show close-up views of one neuron in the respective animal; H&E staining, bar = 10μm.</p

Timeline of the experiment.

<p>Microdiyalsis sampling interval conituously with 1 sample over 8min; Time scale is non linear to allow better overview; VF, ventricular fibrillation; ROSC, return of spontaneous circulation; CPR, cardiopulmonary resuscitation; ECLS, extracorporeal cardiopulmonary life support.</p

CA1 glutamate μmol/l against time.

<p>x-axis: Point of measurement, measurements 8min apart (sampling interval of 8min); y axis: Glutamate (μmol/l; mean values and standard deviation); CA, cardiac arrest; CPR, cardiopulmonary resuscitation; ECLS, extracorporeal cardiopulmonary life support; BL, baseline; ROSC, return of spontaneous circulation.</p

Baseline characteristics.

<p>Baseline characteristics.</p