Objective: To test the feasibility of a neurocognitive test based on operant conditioning in a porcine model of cardiac arrest and cardiopulmonary resuscitation. Furthermore, to characterize the influence of different durations of cardiac arrest on cognitive performance and the accompanying neurohistopathological changes.
Design: Randomized controlled laboratory animal study.
Setting: Animal research facility of a university hospital.
Subjects: Seventeen male domestic pigs.
Interventions: Animals were anesthetized and mechanically ventilated before arterial and pulmonary artery catheters were inserted. Cardiac arrest was induced electrically after randomization of the animals into two groups (n = 7/group) left untreated for either 5 or 8 mins. Cardiopulmonary resuscitation was performed with 100% oxygen and cardiac compressions at 100/min for 5 mins before defibrillation was attempted. Three animals treated identically, with the exception that neither cardiac arrest was induced nor cardiopulmonary resuscitation was performed, served as controls.
Measurements and main results: Hemodynamic variables as well as variables of gas exchange were measured at baseline and 10, 60, 120, 240, and 360 mins after cardiopulmonary resuscitation. Neurocognitive performance was evaluated using a test based on operant conditioning 5 days before and 4 days after cardiopulmonary resuscitation. On the fifth postoperative day, animals were killed and the brains removed for histopathological evaluation of vulnerable brain regions. No noteworthy differences in hemodynamics or gas exchange were observed at baseline or after cardiopulmonary resuscitation. Animals exposed to 8 mins of untreated cardiac arrest showed severe neurocognitive dysfunction, which was statistically significant on postoperative days 2 and 3 in comparison to animals exposed to 5 mins of cardiac arrest or controls. Neurohistopathological evaluation revealed a significantly greater proportion of ischemically damaged neurons in the caudate nucleus and putamen in pigs subjected to 8 mins of cardiac arrest.
Conclusions: Neurocognitive testing is feasible in this setting. Performance worsens with increasing ischemia time and is structurally associated with alterations in the caudate nucleus and the putamen.