Effect of pregabalin on cerebral outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest in rats.
OBJECTIVE
Activation of presynaptic voltage-gated calcium channels and release of glutamate play a central role in neuronal necrosis after cardiopulmonary bypass with deep hypothermic circulatory arrest. Pregabalin binds to the α2-δ subunit of voltage-gated calcium channels resulting in reduced glutamate release. The aim of this study is to evaluate the effect of pregabalin on cerebral outcome after cardiopulmonary bypass with deep hypothermic circulatory arrest through an established rat model allowing long-term survival.


METHODS
Male Sprague-Dawley rats were randomized to receive intraperitoneal injection of 30 mg/kg of pregabalin or an equal amount of normal saline 1 hour before cardiopulmonary bypass (n = 10, each). Rats were cooled to a pericranial temperature of 18°C and underwent deep hypothermic circulatory arrest for 60 minutes. Neurologic performance was assessed at postoperative days 3, 7, and 12. Cognitive performance (Morris water maze) was assessed daily from postoperative day 3 to 12 when histologic assessment was performed.


RESULTS
Neurologic scores were significantly better in the pregabalin group than in the control group at all time points of measurements. Morris water maze latencies were not statistically different between the groups. The percentage of necrotic neurons in the cerebral cortex was significantly less in the pregabalin group compared with the control group (8.6% [interquartile range, 5.0-8.9] vs 13.6% [interquartile range, 6.9-18.6], P = .045), whereas no difference was observed in the hippocampus.


CONCLUSIONS
Preemptive treatment with pregabalin conveyed a beneficial influence on functional and histologic cerebral outcome in rats undergoing 60 minutes of deep hypothermic circulatory arrest after cardiopulmonary bypass without any noticeable side effects.
Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University Health System, Seoul, Korea.
Jae-Kwang
JK
Shim
Department of Anesthesiology, Duke University Medical Center, Durham, NC.
Qing
Q
Ma
Department of Anesthesiology, Duke University Medical Center, Durham, NC.
Zhiquan
Z
Zhang
Department of Anesthesiology, Duke University Medical Center, Durham, NC.
Mihai V
MV
Podgoreanu
Department of Anesthesiology, Duke University Medical Center, Durham, NC; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, Wash. Electronic address: gbmac@uw.edu.
G Burkhard
GB
Mackensen
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects*; D003071:Cognition / Q000187:drug effects; D007274:Injections, Intraperitoneal; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069583:Pregabalin; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D018696:Neuroprotective Agents; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid