• Mingyue Liu, Qingdong Zeng, Yongnan Li, Gang Liu, and Bingyang Ji.
• Department of Cardiopulmonary Bypass, State Key Laboratory of Cardiovascular Medicine, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
• Artif Organs. 2019 Jun 1; 43 (6): 551-560.

AbstractBrain injury associated with deep hypothermic circulatory arrest (DHCA) has been recognized in patients with congenital heart diseases and those undergoing aortic arch surgeries. However, the preclinical investigation of long-term cerebral injury and recovery mechanisms related to DHCA has been restricted to a satisfactory recovery animal model with a determined recovery time. This study aimed to evaluate the feasibility of a long-term surviving DHCA model without blood priming in rats, in order to investigate the pathophysiology of long-term complications in further studies. Twelve Sprague-Dawley rats were divided into 2 groups: sham group (n = 3) and DHCA group (n = 9). The DHCA group was further assigned to the surviving time of postoperative day 2, 14, and 30 (n = 3, respectively). The entire cardiopulmonary bypass (CPB) circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a heater/cooler. A 24-G catheter was cannulated in the branch of the left femoral artery for arterial blood pressure monitoring. Cardiopulmonary bypass was established via the right external jugular vein-right atrium and tail artery. Rats were cooled to a rectal temperature of 18°C, followed by 30 minutes of DHCA with global ischemia. After re-warming for approximately 40 minutes, the animals were weaned from the CPB at 35.5°C. Blood gas and hemodynamic parameters were recorded preoperatively and intraoperatively, and at 2, 14, and 30 days postoperatively. Thereafter, the brains were perfusion fixed and histologically analyzed. All DHCA processes were successfully achieved, and none of the rats died. Blood gas analysis and hemodynamic parameters at each time point were normal, and vital signs of all rats were stable. Histopathologic deficits in the hippocampus (pathological score, surviving hippocampal neurons, and Ki67-positive neurons) manifested after 30 minutes of DHCA, which persisted for at least 14 days and recovered after 30 days. A novel and simple long-term recovery model of DHCA in rats was established in the present study, and histopathologic deficits were observed after clinically relevant 30-minute DHCA durations, in order to determine the 30-day recovery time frame.© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

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