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Ann Thorac Surg 2005;79:1314-1315
© 2005 The Society of Thoracic Surgeons
Department of Cardiothoracic Surgery, Leiden University Medical Center, Mathenesselaan 2, Oegstgeest 2343 HA, the Netherlandse.fbruggemans@lumc.nl
Although serious neurologic sequelae after hypothermic circulatory arrest (HCA) have strongly declined due to increasing experience and improved cerebral protection strategies, there still exists a risk of long-term cognitive deficits that cannot reliably be detected with neuroimaging or routine neurologic examinations. Hagl and colleagues present a study on the feasibility of a porcine model of cognitive dysfunction after HCA. The effects of HCA on spatial learning and memory tasks were investigated using a multi-room maze. The clinical relevance of this model depends on the sensitivity of this behavioral measure to HCA and its relationship to human cognitive skills.
Studies in humans and animals suggest that the hippocampus and adjacent cortical areas play an important role in topographic learning and memory [1]. Recordings of single hippocampal cell activity in animals suggest that the hippocampus functions as a map representing spatial relations of the world and the topographic position of the animal in the world [2]. The negative effects of HCA on spatial learning during the second task of Hagl's study may be related to the high sensitivity of the hippocampus to ischemia [3]. In pigs [4, 5], dogs [6], and rats [7], it was demonstrated that hippocampal neurons, particularly the pyramidal CA1 cells, are sensitive to injury and cell death when exposed to prolonged hypoxia. Dysfunction of CA1 neurons in guinea pigs [8] and rats [9] is associated with impaired spatial learning. Humans with hippocampal lesions after cerebral hypoxia or from other causes also have problems with spatial learning [10, 11].
This study shows that pigs can quickly learn topographical relations between a substantial number of locations in a maze. The impairment in performance following HCA shows a strong parallel with other species, including humans. Thus the pig seems to be a clinically relevant model for evaluating the effectiveness of cerebral protection methods. Nevertheless, there is some uncertainty about the optimal task protocol. It is not entirely clear why performance was only impaired during the second task because the number of items to be remembered was not clearly different between tasks. Although the difference may be explained by the relatively long retention interval during the second task, being associated with a higher working memory load, it may also be related to the requirement that the animals had to shift their searching strategy halfway through the task from one side of the maze to the opposite side. Problems with such strategy shifts, ensuing in perseverance of inadequate responses, are well known in humans and monkeys with frontal cortex and other frontal lobe lesions [12, 13]. Such a deficit cannot be excluded in the pig model because HCA also causes neuronal injury in cortical areas [5, 14]. More certainty about the optimal protocol could be obtained by replicating the current findings, preferably in a larger subject sample. If the strategy shift were crucial, then the error rates should be larger for the second phase of the task than for the first. In that case, the difficulty of the task, and thus its sensitivity to protective procedures, could be simply manipulated by varying the complexity and number of strategy shifts.
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