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Brain 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.

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Deep hypothermia or circulation arrest is widely used during total aortic arch replacement. However, conventional procedures have high morbidity and mortality.1 We use the "branch-first" technique2,3 combined with clamping the distal aorta, incorporating a stented elephant trunk to avoid deep hypothermia and circulation arrest. This technique brings us closer to the goal of arch surgery without cerebral or visceral circulatory arrest and the morbidity of deep hypothermia. Early results are encouraging.

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OBJECTIVE: Cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) are commonly used in cardiac surgery. However, the mortality and morbidity are still high in practice. Developing novel protective stategies and elucidating the underlying mechanisms for the pathophysiological consequences of DHCA have been hampered because of the absence of a satisfactory recovery animal model. The aim of this study was to establish a novel and safe DHCA model without blood priming in rats to study the pathophysiology of potential complications. METHODS: Ten adult male Sprague-Dawley rats (age, 14-16 weeks; weight, 200-300g) were used. The entire CPB circuit consisted of a modified reservoir, a custom-designed small-volume membrane oxygenator, a roller pump and a home-made heat exchanger, all of which were connected via silicon tubing. The volume of the priming solution was less than 10 ml. The right jugular vein, right carotid artery and left femoral artery were cannulated. The blood was drained from the right atrium through the right jugular vein and fed back to the rat via the left femoral artery. CPB was commenced at a full flow rate. The animals were cooled to a pericranial temperature of 18°C and then subjected to 45 minutes of DHCA with global ischemia. Circulatory arrest was followed by rewarming and over 60 minutes of reperfusion. CPB was terminated carefully. Blood in the circuit was centrifuged and slowly transfused to achieve optimal hematocrit. Blood gas and hemodynamic parameters were recorded at each time point before CPB, during CPB and after CPB. RESULTS: All CPB and DHCA processes were achieved successfully. No rat died in our research. Blood gas analyses at different times were normal. Cardiac function and blood pressure were stable after the operation. The vital signs of all the rats were stable. CONCLUSION: The novel augmented venous-drainage CPB and DHCA model in rats could be established successfully without blood priming.

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INTRODUCTION: Aortic arch reconstruction under moderate hypothermia is commonly performed with antegrade cerebral perfusion (ACP) for brain protection; however, hypothermia alone is often solely relied upon for visceral and lower body protection. We investigated whether the addition of simultaneous lower body perfusion to ACP (whole body perfusion - WBP) may ameliorate the metabolic derangements of moderate hypothermic circulatory arrest (MHCA). METHODS: Between 2008 and 2014, 106 consecutive patients underwent elective or emergent aortic arch surgery with MHCA, with either ACP only (44 patients, 66±12 years, 30% female) or WBP (62 patients, 61±15 years, 31% female). Primary outcomes included 30-day/in-hospital mortality, intensive care unit (ICU) and hospital lengths of stay (LOS) and specific parameters of metabolic recovery. RESULTS: There were no significant differences between the groups in 30-day/in-hospital mortality (ACP: 3 (6.8%), WBP: 2 (3.2%); p=0.65), stroke (ACP: 1 (2.3%), WBP: 1 (1.6%); p=1.0) or renal failure (ACP: 2 (4.5%), WBP: 1 (1.5%); p=0.57). In the WBP group, we identified a significant reduction in lactate level at ICU admission (ACP 5.5 vs. WBP 3.5 mmol/L; p=0.002), time to lactate normalization (p=0.014) and median ICU length-of-stay (ACP 3 vs. WBP 1 days; p=0.049). There was no difference in post-operative creatinine (ACP: 104, WBP: 107 µmol/L; p=0.66). After multivariable regression adjustment, perfusion strategy no longer remained an independent predictor of ICU discharge time (p=0.09), however, cardiopulmonary bypass time (p=0.02), age (p=0.012) and emergent surgery (p=0.02) were. CONCLUSIONS: A WBP strategy during aortic arch reconstruction with MHCA may be associated with more rapid normalization of metabolic parameters and reduced ICU length of stay compared to using ACP alone. Further evaluation with a randomized trial is warranted.

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Monitoring cerebral oxygenation with near infrared spectroscopy may identify periods of cerebral desaturation and thereby the patients at risk for perioperative neurocognitive issues. Data regarding the performance of near infrared spectroscopy monitoring during deep hypothermic circulatory arrest are limited. The current study presents data regarding use of a commercially available near infrared spectroscopy monitor during deep hypothermic circulatory arrest in paediatric patients undergoing surgery for congenital heart disease. The cohort included 8 patients, 2 weeks to 6 months of age, who required deep hypothermic circulatory arrest for repair of congenital heart disease. The baseline cerebral oxygenation was 63 +/- 11% and increased to 88 +/- 7% after 15 min of cooling to a nasopharyngeal temperature of 17-18 degrees C on cardiopulmonary bypass. In 5 of 8 patients, the cerebral oxygenation value had achieved its peak value (either >or=90% or no change during the last 2-3 min of cooling on cardiopulmonary bypass). In the remaining 3 patients, additional time on cardiopulmonary bypass was required to achieve a maximum cerebral oxygenation value. The duration of deep hypothermic circulatory arrest varied from 36 to 61 min (43.4 +/- 8 min). After the onset of deep hypothermic circulatory arrest, there was an incremental decrease in cerebral oxygenation to a low value of 53 +/- 11%. The greatest decrease occurred during the initial 5 min of deep hypothermic circulatory arrest (9 +/- 3%). Over the entire period of deep hypothermic circulatory arrest, there was an average decrease in the cerebral oxygenation value of 0.9% per min (range of 0.5 to 1.6% decline per minute). During cardiopulmonary bypass, cooling and deep hypothermic circulatory arrest, near infrared spectroscopy monitoring followed the clinically expected parameters. Such monitoring may be useful to identify patients who have not achieved the highest possible cerebral oxygenation value despite 15 min of cooling on cardiopulmonary bypass. Future studies are needed to define the cerebral oxygenation value at which neurological damage occurs and if interventions to correct the decreased cerebral oxygenation will improve perioperative outcomes.

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