Acute Renal Injury Induced by Deep Hypothermic Circulatory Arrest and Its Early Detection_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

YULei ,  GUTian-xiang , SHIEn-yi , ZHANGGuang-wei , MAONai-hui , CHENGShi

Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, P. R. China;

Corresponding author：

GUTian-xiang, Email: cmugtx@sina.com

Keywords：

Cardiopulmonary bypass; Deep hypothermic circulatory arrest; β-trace protein

DOI：

10.7507/1007-4848.20140024

Video：

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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

1.	Augoustides JG, Pochettino A, Ochroch EA, et al.Renal dysfunction after thoracic aortic surgery requiring deep hypothermic circulatory arrest:definition, incidence, and clinical predictors.J.Cardiothorac Vasc Anesth, 2006, 20 (5):673-677.
2.	Mora Mangano CT, Neville MJ, Hsu PH, et al.Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest.Circulation, 2001, 104 (12 Suppl 1):276-281.
3.	Arnaoutakis GJ, Bihorac A, Martin TD, et al.RIFLE criteria for acute kidney injury in aortic arch surgery.J Thorac Cardiovasc Surg, 2007, 134 (6):1554-1560.
4.	Augoustides JG, Floyd TF, McGarvey ML, et al.Major clinical outcomes in adults undergoing thoracic aortic surgery requiring deep hypothermic circulatory arrest:quantification of organ-based perioperative outcome and detection of opportunities for perioperative intervention.J Cardiothorac Vasc Anesth, 2005, 19 (4):446-452.
5.	Mori Y, Sato N, Kobayashi Y, et al.Acute kidney injury during aortic arch surgery under deep hypothermic circulatory arrest.J Anesth, 2011, 25 (6):799-804.
6.	Stafford-Smith M, Patel UD, Phillips-Bute BG, et al.Acute kidney injury and chronic kidney disease after cardiac surgery.Adv Chronic Kidney Dis, 2008, 15 (3):257-277.
7.	Nollert G, Nagashima M, Bucerius J, et al.Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest.I.Gaseous microemboli.J Thorac Cardiovasc Surg, 1999, 117 (6):1166-1171.
8.	Undar A, Calhoon JH, Cossman RM, et al.The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow in dogs.J Cardiothorac Vasc Anesth, 1998, 12 (1):126-128.
9.	Wang Q, Yang J, Long C, et al.Hyperoxia management during deep hypothermia for cerebral protection in circulatory arrest rabbit model.ASAIO J, 2012, 58 (4):330-336.
10.	Pan X, Sun L, Ma W, et al.Overactivation of poly (adenosine phosphate-ribose) polymerase 1 and molecular events in neuronal injury after deep hypothermic circulatory arrest:study in a rabbit model.J Thorac Cardiovasc Surg, 2007, 134 (5):1227-1233.
11.	王旭冬, 车妙琳, 谢波, 等.急性肾损伤定义及分期系统评估心脏手术患者预后的临床价值.中国胸心血管外科临床杂志, 2012, 19 (6):619-623.
12.	杨勇, 李小密, 李菲, 等.主动脉弓置换术后急性肾损伤发生的危险因素分析.中国胸心血管外科临床杂志, 2011, 18 (2):109-113.
13.	Andersson LG, Ekroth R, Bratteby LE, et al.Acute renal failure after coronary surgery-a study of incidence and risk factors in 2009 consecutive patients.Thorac Cardiovasc Surg, 1993, 41 (4):237-241.
14.	Andersson LG, Bratteby LE, Ekroth R, et al.Renal function during cardiopulmonary bypass:influence of pump flow and systemic blood pressure.Eur J Cardiothorac Surg, 1994, 8 (11):597-602.
15.	Donadio CS, urinary markers of early impairment of GFR in chronic kidney disease patients:diagnostic accuracy of urinary β-trace protein Am J Physiol Renal Physiol, 2010, 299 (6):F1407-F1423.
16.	Prigent A.Monitoring renal function and limitations of renal function tests.Semin Nucl Med, 2008, 38 (1):32-46.
17.	Bianchi C, Donadio C, Tramonti G.Noninvasive methods for the measurement of total renal function.Nephron, 1981, 28 (2):53-57.
18.	Supavekin S, Zhang W, Kucherlapati R, et al.Differential gene expression following early renal ischemia/reperfusion.Kidney Int, 2003, 63 (5):1714-1724.
19.	Mårtensson J, Bell M, Oldner A, et al.Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury.Intensive Care Med, 2010, 36 (8):1333-1340.
20.	Mori K, Lee HT, Rapoport D, et al.Endocytic delivery of lipocalinsiderophore-iron complex rescues the kidney from ischemia-reperfusion injury.J Clin Invest, 2005, 115 (3):610-621.
21.	Koyner JL, Garg AX, Coca SG, et al.Biomarkers predict progression of acute kidney injury after cardiac surgery.J Am Soc Nephrol, 2012, 23 (5):905-914.
22.	Leone MG, Haq HA, Saso L.Lipocalin type prostaglandin D-synthase:which role in male fertility? Contraception, 2002, 65 (4):293-295.
23.	Urade Y, Hayaishi O.Prostaglandin D synthase:structure and function.Vitam Horm, 2000, 58:89-120.
24.	Benlamri A, Nadarajah R, Yasin A, et al.Development of a beta-trace protein based formula for estimation of glomerular filtration rate.Pediatr Nephrol, 2010, 25 (3):485-490.

1. Augoustides JG, Pochettino A, Ochroch EA, et al.Renal dysfunction after thoracic aortic surgery requiring deep hypothermic circulatory arrest:definition, incidence, and clinical predictors.J.Cardiothorac Vasc Anesth, 2006, 20 (5):673-677.
2. Mora Mangano CT, Neville MJ, Hsu PH, et al.Aprotinin, blood loss, and renal dysfunction in deep hypothermic circulatory arrest.Circulation, 2001, 104 (12 Suppl 1):276-281.
3. Arnaoutakis GJ, Bihorac A, Martin TD, et al.RIFLE criteria for acute kidney injury in aortic arch surgery.J Thorac Cardiovasc Surg, 2007, 134 (6):1554-1560.
4. Augoustides JG, Floyd TF, McGarvey ML, et al.Major clinical outcomes in adults undergoing thoracic aortic surgery requiring deep hypothermic circulatory arrest:quantification of organ-based perioperative outcome and detection of opportunities for perioperative intervention.J Cardiothorac Vasc Anesth, 2005, 19 (4):446-452.
5. Mori Y, Sato N, Kobayashi Y, et al.Acute kidney injury during aortic arch surgery under deep hypothermic circulatory arrest.J Anesth, 2011, 25 (6):799-804.
6. Stafford-Smith M, Patel UD, Phillips-Bute BG, et al.Acute kidney injury and chronic kidney disease after cardiac surgery.Adv Chronic Kidney Dis, 2008, 15 (3):257-277.
7. Nollert G, Nagashima M, Bucerius J, et al.Oxygenation strategy and neurologic damage after deep hypothermic circulatory arrest.I.Gaseous microemboli.J Thorac Cardiovasc Surg, 1999, 117 (6):1166-1171.
8. Undar A, Calhoon JH, Cossman RM, et al.The effects of pulsatile cardiopulmonary bypass on cerebral and renal blood flow in dogs.J Cardiothorac Vasc Anesth, 1998, 12 (1):126-128.
9. Wang Q, Yang J, Long C, et al.Hyperoxia management during deep hypothermia for cerebral protection in circulatory arrest rabbit model.ASAIO J, 2012, 58 (4):330-336.
10. Pan X, Sun L, Ma W, et al.Overactivation of poly (adenosine phosphate-ribose) polymerase 1 and molecular events in neuronal injury after deep hypothermic circulatory arrest:study in a rabbit model.J Thorac Cardiovasc Surg, 2007, 134 (5):1227-1233.
11. 王旭冬, 车妙琳, 谢波, 等.急性肾损伤定义及分期系统评估心脏手术患者预后的临床价值.中国胸心血管外科临床杂志, 2012, 19 (6):619-623.
12. 杨勇, 李小密, 李菲, 等.主动脉弓置换术后急性肾损伤发生的危险因素分析.中国胸心血管外科临床杂志, 2011, 18 (2):109-113.
13. Andersson LG, Ekroth R, Bratteby LE, et al.Acute renal failure after coronary surgery-a study of incidence and risk factors in 2009 consecutive patients.Thorac Cardiovasc Surg, 1993, 41 (4):237-241.
14. Andersson LG, Bratteby LE, Ekroth R, et al.Renal function during cardiopulmonary bypass:influence of pump flow and systemic blood pressure.Eur J Cardiothorac Surg, 1994, 8 (11):597-602.
15. Donadio CS, urinary markers of early impairment of GFR in chronic kidney disease patients:diagnostic accuracy of urinary β-trace protein Am J Physiol Renal Physiol, 2010, 299 (6):F1407-F1423.
16. Prigent A.Monitoring renal function and limitations of renal function tests.Semin Nucl Med, 2008, 38 (1):32-46.
17. Bianchi C, Donadio C, Tramonti G.Noninvasive methods for the measurement of total renal function.Nephron, 1981, 28 (2):53-57.
18. Supavekin S, Zhang W, Kucherlapati R, et al.Differential gene expression following early renal ischemia/reperfusion.Kidney Int, 2003, 63 (5):1714-1724.
19. Mårtensson J, Bell M, Oldner A, et al.Neutrophil gelatinase-associated lipocalin in adult septic patients with and without acute kidney injury.Intensive Care Med, 2010, 36 (8):1333-1340.
20. Mori K, Lee HT, Rapoport D, et al.Endocytic delivery of lipocalinsiderophore-iron complex rescues the kidney from ischemia-reperfusion injury.J Clin Invest, 2005, 115 (3):610-621.
21. Koyner JL, Garg AX, Coca SG, et al.Biomarkers predict progression of acute kidney injury after cardiac surgery.J Am Soc Nephrol, 2012, 23 (5):905-914.
22. Leone MG, Haq HA, Saso L.Lipocalin type prostaglandin D-synthase:which role in male fertility? Contraception, 2002, 65 (4):293-295.
23. Urade Y, Hayaishi O.Prostaglandin D synthase:structure and function.Vitam Horm, 2000, 58:89-120.
24. Benlamri A, Nadarajah R, Yasin A, et al.Development of a beta-trace protein based formula for estimation of glomerular filtration rate.Pediatr Nephrol, 2010, 25 (3):485-490.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Acute Renal Injury Induced by Deep Hypothermic Circulatory Arrest and Its Early Detection

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