Longitudinal assessment of neurocognitive function in rats after cardiopulmonary bypass: evidence for long-term deficits.

ABSTRACT

OBJECTIVE(S) Neurologic and neurocognitive dysfunction after cardiopulmonary bypass (CPB) have been shown in both clinical and experimental settings. Although short-term outcome has been evaluated in rats, the assessment of neurocognitive dysfunction with long-term follow-up has not been reported in experimental CPB models. The objective of this study was to evaluate the effects of CPB on long-term neurocognitive function in the rat. DESIGN: Prospective, interventional study. SETTING: A university research laboratory. PARTICIPANTS: Male Sprague-Dawley rats. INTERVENTIONS: Sprague-Dawley rats were randomized to either CPB (n = 19) or sham-operated groups (n = 17). On days 3, 7, and 14 and at 6 weeks after surgery, the rats were submitted to standardized neurologic testing (Neuroscore). In addition, the animals underwent cognitive testing in the Morris water maze (MWM), including basic, probe, and reversal trial protocols during the first 19 postoperative days (short-term cognitive outcome) and then repeated 6 weeks after surgery (long-term cognitive outcome). MEASUREMENTS AND MAIN RESULTS: The CPB group had worse Neuroscores (day 3, 5[2]; day 7, 7[2]; day 14, 5[1]; 6 weeks, 5[1]) compared with the sham group (day 3, 7[2]; day 7, 7[1]; day 14, 7[1]; 6 weeks, 7[1]) at all time points tested (p < 0.05). In the MWM, the CPB group showed both short-term and persistent long-term neurocognitive dysfunction. CONCLUSIONS: Compared with sham-operated controls, rats undergoing CPB showed worse neurologic and neurocognitive outcome early after surgery. Importantly, long-term deficits also persisted at 6 weeks after surgery.