Objective To establish a novel animal model of deep hypothermic circulatory arrest (DHCT) in rabbits without thoracotomy, and investigate acute kidney injury (AKI) induced by DHCT and early novel biomarkers of AKI. Methods Forty-two New Zealand big ear rabbits (3.5-4.0 kg, male or female) were randomly divided into 2 groups with 21 rabbits in each group. Cardiopulmonary bypass (CPB) was established via the right carotid artery and jugular vein in both groups. In Group A, CPB continued when the rectal temperature was maintained at 28℃. In group B, DHCT started when the rectal temperature reached 16℃ to 18℃ and lasted for 60 minutes before CPB was resumed and rewarming was started. The rectal temperature was restored to 35℃ within 30 minutes, then CPB was maintained for 30 minutes. CPB time was same in both groups. Preoperatively and 6 hours, 24 hours and 48 hours after the operation, venous blood samples were taken to examine serum creatinine (Cr) and β-trace protein (β-TP), and urine samples were taken to examine neutrophil gelatinase-associated lipocalin (NGAL). Four rabbits were sacrificed at respective above time points to measure renal malondialdehyde (MDA) content. Hematoxylin-Eosin (HE) staining, TUNEL assay and transmission electron microscopy were used to examine morphological changes of renal tubular epithelial cells (TECs). Results Four rabbits died in group A and five rabbits died in Group B during the experiment.(1)Blood Cr:There was no statistical difference between different time points in Group A (P > 0.05). In Group B, serum Cr at 24 hours after the operation was significantly higher than other time points, and also significantly higher than that of group A (P < 0.05).(2)Blood β-TP and urinary NGAL:There was no statistical difference between different time points in Group A (P > 0.05). In Group B, blood β-TP and urinary NGAL at the time of 6 hours, 24 hours and 48 hours postoperatively were significantly higher than preoperative levels (P < 0.05). Blood β-TP and urinary NGAL at the time of 24 hours postoperatively were significantly higher than other time points (P < 0.05). Blood β-TP and urinary NGAL at the time of 6 hours, 24 hours and 48 hours postoperatively were significantly higher than those of group A (P < 0.05).(3)Renal MDA content of Group B at the time of 24 hours postoperatively was significantly higher than other time points as well as that of Group A (P < 0.05).(4) HE staining showed serious pathological injuries of renal TECs at the time of 24 hours postoperatively in Group B. There was no significant pathological injury of renal TECs at the time of 24 hours postoperatively in Group A. (5)TUNEL-positive rate of group B at the time of 24 hours postoperatively was significantly higher than other time points as well as that of group A (P < 0.05).(6)Transmission electron microscope showed serious pathological injuries of renal TECs organelles at the time of 24 hours postoperatively in Group B. There was no significant pathological injury of renal TECs organelles in Group A. Conclusions This DHCT rabbit model without thoracotomy is a simple, convenient, and economical animal model with long-term animal survival for the study of DHCT-induced organ injury. AKI is most serious at the time of 24 hours after DHCA. Blood β-TP and urinary NGAL can be used as early biomarkers of DHCT-induced AKI.

Citation： YULei, GUTian-xiang, SHIEn-yi, ZHANGGuang-wei, MAONai-hui, CHENGShi. Acute Renal Injury Induced by Deep Hypothermic Circulatory Arrest and Its Early Detection. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2014, 21(1): 90-96. doi: 10.7507/1007-4848.20140024 Copy

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