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Jie Xu,1,2 Liujun Tao,1 Liangyan Jiang,1 Jie Lai,1 Juntao Hu,1 Zhanhong Tang1 1Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Department of Critical Care Medicine, Suining Central Hospital, Suining, Sichuan, 629000, People’s Republic of ChinaCorrespondence: Zhanhong Tang; Juntao Hu, Department of Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, Guangxi, 530021, Tel +86 13978816316 ; +86 18978866565, People’s Republic of China, Email tangzhanhong139@sina.com; hujuntao80@126.comPurpose: Sepsis-associated acute lung injury (SA-ALI) is a common complication in patients with sepsis, contributing to high morbidity and mortality. Excessive inflammation and oxidative stress are crucial contributors to lung injury in sepsis. This study aims to examine the protective effects of moderate hypothermia on SA-ALI and explore the underlying mechanisms.Methods: Sepsis was induced in rats through cecal ligation and puncture followed by intervention with moderate hypothermia (32– 33.9°C). Blood, bronchoalveolar lavage fluid, and lung tissues were collected 12 hours post-surgery. Inflammatory responses, oxidative injury, SA-ALI-related pathophysiological processes, and Keap1/GSK3β/Nrf2/GPX4 signaling in septic rats were observed by ELISA, lung W/D ratio, immunohistochemistry, immunofluorescence, histological staining, Western blotting, RT-qPCR, and TEM assays.Results: Moderate hypothermia treatment alleviated lung injury in septic rats, reflected in amelioration of pathological changes in lung structure and improved pulmonary function. Further, moderate hypothermia reduced arterial blood lactate production and suppressed the expression of inflammatory factors IL-1β, IL-6, and TNF-α; downregulated ROS, MDA, and redox-active iron levels; and restored GSH and SOD content. TEM results demonstrated that moderate hypothermia could mitigate ferroptosis in PMVECs within lung tissue. The underlying mechanism may involve regulation of the Keap1/Nrf2/SLC7A11/GPX4 signaling pathway, with the insulin pathway PI3K/Akt/GSK3β also playing a partial role.Conclusion: Collectively, we illustrated a novel potential therapeutic mechanism in which moderate hypothermia could alleviate ferroptosis induced by excessive inflammation and oxidative stress via the regulation of Keap1/GSK3β/Nrf2/GPX4 expression, hence ameliorating acute lung injury in sepsis.Keywords: moderate hypothermia, sepsis, acute lung injury, ferroptosis, Nrf2, inflammation

IntroductionThe impact of different degrees of hypothermia in patients undergoing type A aortic dissection (TAAD) repair remains controversial. The purpose of this study was to compare the clinical outcomes of patients who received deep hypothermic circulatory arrest (DHCA) (

Abstract Objective We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30–32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). Methods We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25–28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30–32 °C) with distal aortic perfusion (s-TAR group). Results The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. Conclusions s-TAR under mild hypothermia (30–32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR.

Objective: We designed a simplified total arch reconstruction (s-TAR) technique which could be performed under mild hypothermia (30–32 °C) with distal aortic perfusion. This study aimed to compare its efficacy of organ protection with the conventional total arch reconstruction (c-TAR). Methods: We reviewed the clinical data of 195 patients who had ascending aortic aneurysm with extended aortic arch dilation and underwent simultaneous ascending aorta replacement and TAR procedure between January 2018 and December 2022 in our center. 105 received c-TAR under moderate hypothermia (25–28 °C) with circulatory arrest (c-TAR group); rest 90 received s-TAR under mild hypothermia (30–32 °C) with distal aortic perfusion (s-TAR group). Results: The s-TAR group demonstrated shorter CPB time, cross-clamp time and lower body circulatory arrest time compared with the c-TAR group. The 30-day mortality was 2.9% for the c-TAR group and 1.1% for the s-TAR group (P = 0.043). The mean duration of mechanical ventilation was shorter in the s-TAR group. Paraplegia was observed in 4 of 105 patients (3.8%) in the c-TAR group, while no such events were observed in the s-TAR group. The incidence of temporary neurologic dysfunction was significantly higher in the c-TAR group. The incidence of permanent neurologic dysfunction also showed a tendency to be higher in the c-TAR group, without statistical significance. Furthermore, the incidence of reoperation for bleeding were significantly lower in the s-TAR group. The rate of postoperative hepatic dysfunction and all grades of AKI was remarkably lower in the s-TAR group. The 3-year survival rate was 95.6% in the s-TAR group and 91.4% in the c-TAR group. Conclusions: s-TAR under mild hypothermia (30–32℃) with distal aortic perfusion is associated with lower mortality and morbidity, offering better neurological and visceral organ protection compared with c-TAR. [ABSTRACT FROM AUTHOR]

We report the case of a 72-year-old male patient who presented with a progressive aortic arch aneurysm. To reduce surgical trauma, we planned the procedure using an upper partial sternotomy with continuous cardiac perfusion and moderate hypothermia. Two vents were inserted to provide sufficient relief to the heart during perfusion. The heart was perfused continuously under flow and pressure control. To treat the aneurysm, a Vascutec™ Thoraflex Hybrid prosthesis was implanted. Despite the minimally invasive approach of partial sternotomy and beating heart combined with moderate hypothermia, the procedure was performed safely, quickly and without complications. The operation required precise pre-planning of the anatomy, outstanding surgical expertise and excellent interdisciplinary cooperation with the anaesthetist and clinical perfusionist. [ABSTRACT FROM AUTHOR]

Introduction: In open heart surgery such as Coronary artery Bypass Grafting, valve repair or replacement, or some congenital heart disease, patients are connected to the Cardiopulmonary bypass machine [1]. Cardiopulmonary bypass machine pumps the blood around the body while the heart is stopped and provides a bloodless field during cardiac surgery. Since an extracorporeal circuit is incorporated to the patient, there are observed abnormal physiological events during Cardiopulmonary bypass. These events include hemodilution, interstitial fluid accumulation, complement activation and depression of immune system. Cardiopulmonary bypass is associated with an acute phase reaction of protease cascades, leucocyte, and platelet activation that result in tissue injury [2, 3] and limited functional reserve. For many years was believed that Cardiopulmonary bypass under hypothermia is much safer. The main reason for “cooling body” is to protect the brain, heart and organs during cardiopulmonary bypass through reducing body metabolic rate [4]. During more recent years, according to many studies, it is shown that Cardiopulmonary bypass under Normothermia has much more advantages compared to Moderate Hypothermia. The aim of this study was to compare and examine which method has advantages in terms of clinical outcome, morbidity and mortality. Patients and methods. 60 patients were selected, who were scheduled for Coronary artery Bypass Grafting x 3, were enrolled in this study. Results: According to the primary variables (Troponin I, Lactic Acid) and also secondary variables of our study, resulted that Cardiopulmonary bypass in Normothermia has superiority compare to Moderate Hypothermia in patients that underwent Coronary artery Bypass Grafting. Conclusion: According to our data and literature [15, 16, 17], we concluded that Cardiopulmonary bypass in Coronary artery Bypass Grafting under Normothermia has advantages vs Moderate Hypothermia and Troponin I and Lactic Acid are very good biomarkers that show us if heart and organs perfusion/protection is adequate during this procedure.

Objectives: Aortic surgeries performed under moderate hypothermia require antegrade cerebral perfusion. The influence of retrograde cerebral perfusion under moderate hypothermic circulatory arrest remains unknown. To clarify this effect, this study aimed to compare the early outcomes of retrograde versus antegrade cerebral perfusion under moderate hypothermia for hemiarch replacement. Methods: Between March 2009 and April 2020, 391 hemiarch replacements under moderate hypothermic circulatory arrest via median sternotomy were performed at our institution. Of these, 70 involved retrograde perfusion and 162 involved antegrade perfusion. Propensity score matching was used to compare 61 pairs of retrograde and antegrade cases. Results: Retrograde and antegrade strategy under moderate hypothermia resulted in comparable operative mortality (3.3% vs. 1.6%, P > 0.99), permanent neurological deficits (8.5% vs. 6.6%, P > 0.99), and temporary neurological deficits (24.6% vs. 39.3%, P = 0.33). Retrograde surgery was associated with shorter circulatory arrest times (31.4 ± 8.2 min vs. 37.4 ± 12.2 min, P = 0.005) and fewer red blood cell transfusions (4.6 ± 3.9 units vs. 8.2 ± 5.1 units, P < 0.001) than those with antegrade surgery. Conclusions: Retrograde cerebral perfusion under moderate hypothermia for hemiarch replacement yields excellent operative outcomes, equivalent to those achieved using an antegrade strategy. [ABSTRACT FROM AUTHOR]

Aim: Cardiac surgery requiring cardiopulmonary bypass (CPB) can result in renal and cerebral injury. Intraoperative tissue hypoxia could contribute to such organ injury. Hypothermia, however, may alleviate organ hypoxia. Therefore, we tested whether moderate hypothermia (30°C) improves cerebral and renal tissue perfusion and oxygenation during ovine CPB. Methods: Ten sheep were studied while conscious, under stable anesthesia, and during 3 h of CPB. In a randomized within‐animal cross‐over design, five sheep commenced CPB at a target body temperature of 30°C (moderate hypothermia). After 90 min, the body temperature was increased to 36°C (standard procedure). The remaining five sheep were randomized to the opposite order of target body temperature. Results: Compared with the standard procedure, moderately hypothermic CPB reduced renal oxygen delivery (−34.8% ± 19.6%, P = 0.003) and renal oxygen consumption (−42.7% ± 35.2%, P = 0.04). Nevertheless, moderately hypothermic CPB did not significantly alter either renal cortical or medullary tissue PO2. Moderately hypothermic CPB also did not significantly alter cerebral perfusion, cerebral tissue PO2, or cerebral oxygen saturation compared with the standard procedure. Compared with the anesthetized state, the standard procedure reduced renal medullary PO2 (−21.0 ± 13.8 mmHg, P = 0.014) and cerebral oxygen saturation (65.0% ± 7.0% to 55.4% ± 9.6%, P = 0.022) but did not significantly alter either renal cortical or cerebral PO2. Conclusion: Ovine experimental CPB leads to renal medullary tissue hypoxia. Moderately hypothermic CPB did not improve cerebral or renal tissue oxygenation. In the kidney, this is probably because renal tissue oxygen consumption is matched by reduced renal oxygen delivery. [ABSTRACT FROM AUTHOR]

Abstract Background To prevent cardiac collapse and to protect cerebral function, hypothermic cardiopulmonary bypass is established before resternotomy. However, ventricular fibrillation under hypothermia facilitates left ventricular distension, which causes irreversible myocardial damage when the patient has aortic regurgitation. We report a case of successful management in preventing ventricular fibrillation under hypothermia by using nifekalant. Case presentation A 56-year-old male, who had been performed a David operation, was scheduled for a Bentall operation for a pseudo aortic aneurysm with severe aortic regurgitation. After inducing anesthesia, we administered intravenous nifekalant and a vent tube was inserted into the left ventricle under one-lung ventilation. Extracorporeal circulation was established and resternotomy started after cooling to 27 °C. Although severe bradycardia and QT prolongation were observed, ventricular fibrillation did not occur until aortic cross-clamping. Conclusion Combining maintaining cerebral perfusion and avoiding left ventricle distension during hypothermia was successfully managed with nifekalant in our redo cardiac patient with aortic regurgitation.

Moderate hypothermia has been used to improve outcomes in comatose out‐of‐hospital cardiac arrest survivors during the past two decades, although the effects remain controversial. We have recently shown in an experimental study that myocardial electrophysiological and mechanical relationships were altered during moderate hypothermia. Electromechanical window positivity increased, and electrical dispersion of repolarization decreased, both of which are changes associated with decreased arrhythmogenicity in clinical conditions. Mechanical dispersion, a parameter also linked to arrhythmic risk, remained unaltered. Whether corresponding electrophysiological and mechanical changes occur in humans during moderate hypothermia, has not been previously explored. Twenty patients with normal left ventricular function were included. Measurements were obtained at 36 and 32°C prior to ascending aortic repair while on partial cardiopulmonary bypass and at 36°C after repair. Registrations were performed in the presence of both spontaneous and comparable paced heart rate during standardized loading conditions. The following electrical and mechanical parameters were explored: (1) Electromechanical window, measured as time difference between mechanical and electrical systole, (2) dispersion of repolarization from ECG T‐wave, and (3) mechanical dispersion, measured as segmental variation in time to peak echocardiographic strain. At moderate hypothermia, mechanical systolic prolongation (425 ± 43–588 ± 67 ms, p < 0.001) exceeded electrical systolic prolongation (397 ± 49–497 ± 79 ms, p < 0.001), whereby, electromechanical window positivity increased (29 ± 30–86 ± 50 ms, p < 0.001). Dispersion of repolarization and mechanical dispersion remained unchanged. Corresponding electrophysiological and mechanical relationships were present at comparable paced heart rates. After rewarming, the increased electromechanical window was reversed in the presence of both spontaneous and paced heart rates. Moderate hypothermia increased electromechanical window positivity, while dispersion of repolarization and mechanical dispersion remained unchanged. This impact of hypothermia may be clinically relevant for selected groups of patients after cardiac arrest. [ABSTRACT FROM AUTHOR]

Objective. To estimate a security of application of moderate hypothermia while performing the aortal arch reconstruction in new-born babies in conditions of selective antegrade cerebral perfusion. Materials and methods. In 2010-2019 yrs period in Amosov National Institute of Cardiovascular Surgery and Scientific-Practical Medical Centre of Pediatric Cardiology and Cardio-Surgery in 64 new-born babies the aortal arch reconstruction was performed in conditions of selective antegrade cerebral perfusion in moderate hypothermia. In the investigation only patients with a two-ventricle physiology, in whom further two-ventricular correction was conducted, were included. There were 48 (75%) boys and 16 (25%) girls. Median age of the patients was (1.6 ± 0.8) mo, median body mass - (3.8 ± 1.1) kg, median square of the body surface - (0.24 ± 0.04) m². Echocardiographic investigation and neurosonography were the main diagnostic procedures. Results. Hospital mortality have constituted 4.7% (3 patients died). The death cases were not connected with the brain protection procedure. Duration of artificial blood circulation period have had constituted (138.4 ± 58.8) min at average, aortal clamping - (83.1 ± 40 min), selective antegrade cerebral perfusion - (24.4 ± 8.8) min. In 10 (15,6%) patients in early postoperative period the sternum persisted open. In 4 (6.2%) patients in early postoperative period convulsions were noted, which were treated successfully medicinally. Median stay in the Department of Reanimation and Intensive Therapy have constituted (7.1 ± 4.1) days. In late follow-up period the patients were seen from 1 mo till 8.5 yrs. No one patient died. While elective neurosonography conduction the brain pathological changes were absent. The neurological complications symptoms were absent as well. Conclusion. Selective antegrade cerebral perfusion with moderate hypothermia constitutes effective and secure method of the brain protection while performance of the aortal arch reconstruction in new-born babies, using median surgical approach in conditions of artificial blood circulation.

Objectives: Targeted temperature management (32-36°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts.Design: Prospective clinical study, from June 2015 to May 2018.Setting: Cardiothoracic surgery operation room, Oslo University Hospital.Patients: Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included.Interventions: Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36°C, 32°C prior to graft-replacement, and at 36°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions.Measurements and Main Results: Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ± 170 to 1,156 ± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ± 0.07 and 0.57 ± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ± 0.05 and 0.47 ± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored.Conclusions: In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming. [ABSTRACT FROM AUTHOR]

Background: To prevent cardiac collapse and to protect cerebral function, hypothermic cardiopulmonary bypass is established before resternotomy. However, ventricular fibrillation under hypothermia facilitates left ventricular distension, which causes irreversible myocardial damage when the patient has aortic regurgitation. We report a case of successful management in preventing ventricular fibrillation under hypothermia by using nifekalant. Case presentation: A 56-year-old male, who had been performed a David operation, was scheduled for a Bentall operation for a pseudo aortic aneurysm with severe aortic regurgitation. After inducing anesthesia, we administered intravenous nifekalant and a vent tube was inserted into the left ventricle under one-lung ventilation. Extracorporeal circulation was established and resternotomy started after cooling to 27 °C. Although severe bradycardia and QT prolongation were observed, ventricular fibrillation did not occur until aortic cross-clamping. Conclusion: Combining maintaining cerebral perfusion and avoiding left ventricle distension during hypothermia was successfully managed with nifekalant in our redo cardiac patient with aortic regurgitation. [ABSTRACT FROM AUTHOR]

The development of pathological or compensatory-and-adaptive reactions in homoeothermic animals during various periods of hypothermia can be caused by shifts in the respiratory functions of the mitochondria. Short-term hypothermia promoted an increase in the rates of the glutamate- and succinate-dependent respiration of mitochondria. Phosphorylation rate increased as well, while oxidative phosphorylation coefficient (P/O), respiratory control, and 2,4-DNP sensitivity depended. Changes in respiratory characteristics in the dynamics of prolonged hypothermia depends on the type of substrate. Prolongation of hypothermia to 1 h was associated with further intensification of succinate-dependent respiration, decrease in P/O and respiratory control, while prolongation of hypothermia to 3 h led to their normalization. The majority of respiratory characteristics of glutamate-dependent respiration did not change under these conditions and their levels were the same as during short-term hypothermia. [ABSTRACT FROM AUTHOR]

Hypothermia has multiple physiological effects, including decreasing metabolic rate and oxygen consumption (VO 2 ). There are few human data about the magnitude of change in VO 2 with decreases in core temperature. We aimed to quantify to magnitude of reduction in resting VO 2 as we reduced core temperature in lightly sedated healthy individuals. After informed consent and physical screening, we cooled participants by rapidly infusing 20 mL/kg of cold (4°C) saline intravenously and placing surface cooling pads on the torso. We attempted to suppress shivering using a 1 mcg/kg intravenous bolus of dexmedetomidine followed by titrated infusion at 1.0 to 1.5 μg/(kg·h). We measured resting metabolic rate VO 2 through indirect calorimetry at baseline (37°C) and at 36°C, 35°C, 34°C, and 33°C. Nine participants had mean age 30 (standard deviation 10) years and 7 (78%) were male. Baseline VO 2 was 3.36 mL/(kg·min) (interquartile range 2.98-3.76) mL/(kg·min). VO 2 was associated with core temperature and declined with each degree decrease in core temperature, unless shivering occurred. Over the entire range from 37°C to 33°C, median VO 2 declined 0.7 mL/(kg·min) (20.8%) in the absence of shivering. The largest average decrease in VO 2 per degree Celsius was by 0.46 mL/(kg·min) (13.7%) and occurred between 37°C and 36°C in the absence of shivering. After a participant developed shivering, core body temperature did not decrease further, and VO 2 increased. In lightly sedated humans, metabolic rate decreases around 5.2% for each 1°C decrease in core temperature from 37°C to 33°C. Because the largest decrease in metabolic rate occurs between 37°C and 36°C, subclinical shivering or other homeostatic reflexes may be present at lower temperatures.

Objective: To assess the impact of hypothermic neural rescue for perinatal asphyxia at birth on healthcare costs of survivors aged 6-7 years, and to quantify the relationship between costs and overall disability levels.Design: 6-7 years follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) trial.Setting: Community study including a single parental questionnaire to collect information on children's healthcare resource use.Patients: 130 UK children (63 in the control group, 67 in the hypothermia group) whose parents consented and returned the questionnaire.Interventions: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone.Main Outcome Measures: Healthcare resource usage and costs over the preceding 6 months.Results: At 6-7 years, mean (SE) healthcare costs per child were £1543 (£361) in the hypothermia group and £2549 (£812) in the control group, giving a saving of -£1005 (95% CI -£2734 to £724). Greater levels of overall disability were associated with progressively higher costs, and more parents in the hypothermia group were employed (64% vs 47%). Results were sensitive to outlying observations.Conclusions: Cost results although not significant favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. Estimates were however sensitive to the care requirements of two seriously ill children in the control group. A quantification of the relationship between costs and levels of disability experienced will be useful to healthcare professionals, policy makers and health economists contemplating the long-term economic consequences of perinatal asphyxia and hypothermic neural rescue.Trial Registration Number: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials. gov number NCT01092637. [ABSTRACT FROM AUTHOR]

Background: An increasing number of patients addicted to opium are experiencing awareness during coronary artery bypass surgery (CABG) as a result of tolerance to anesthetics. Objectives: This research was primarily intended to determine the potential diminishing effects of moderate hypothermia on anesthetic dosage and recall of anesthesia during the procedure. Methods: In this double-blind randomized controlled trial, a total of 80 CABG candidates with known addiction to opium were divided into two groups: one normothermic (N) and the other moderately hypothermic (H), both undergoing induction as well as close monitoring from September 2014 to January 2016. The candidates were initially set for a target bispectral index (BIS) score of between 40 and 60. As the score rose to 60, an additional dose of propofol was administered, alongside rise in blood pressure and tear-shedding. To enhance the accuracy of our evaluation of anesthetic depth, we also used two questionnaires to test candidates’ recall filled with the assistance of a colleague 24 hours following surgery. Independent-samples t-test and chi-square test were used by SPSS v 18 for data analysis. Results: Eighty patients were studied in two groups of normothermic (N) (n = 40) and hypothermic (H) (n = 40). Given similar demographic data as well as the duration of surgery, we arrived at a propofol dose of 122.52±13.11 cc for normothermic patients and 101.28±14.06 cc for hypothermic subjects (p=0.001). As for fentanyl, the total required sum came up to 39.60±21.04 cc and 31.72±5.81 cc for the above-mentioned groups in order (p=0.025). Moreover, the post-operative interview showed that there was no report of a patient with memory recall following surgery. Conclusions: Moderate hypothermia can substantially reduce the need for anesthetics in patients with addiction to opium when undergoing CABG surgery. Trial registration: This study is registered in Iranian Registry of Clinical Trials with registration number of IRCT2014050513159N5. Funding: This research was supported financially by the Research Council of Mashhad University of Medical Sciences (grant number 920405).

Moderate hypothermia (MH) used as treatment for neurological diseases has a protective effect; however, its mechanism remains unclear. Neuronal autophagy is a fundamental pathological process of early brain injury in subarachnoid hemorrhage (SAH). We found that moderate activation of autophagy can reduce nerve cells damage. In this study, We found that MH can moderately increase the level of autophagy in nerve cells and improve the neurological function in rats. This type of autophagy activation is dependent on extracellular signal-regulated kinase (ERK) signaling pathways. The level of neuronal autophagy was down-regulated significantly by using U0126, an ERK signaling pathway inhibitor. In summary, these results suggest that MH can moderately activate neuronal autophagy through ERK signaling pathway, reduce nerve cell death, and produce neuroprotective effects. [ABSTRACT FROM AUTHOR]

Background In this prospective, single-center, observational study, we investigated the association between repeated short periods of circulatory arrest with moderate hypothermia during pulmonary endarterectomy (PEA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and different neuropsychological dimensions. Methods We examined 70 patients with CTEPH, >18 to 80 years of age, who had been treated with PEA. Neuropsychological testing was performed. Results Learning ability and delayed memory remained well within the normal range for patients’ age. We found a statistically significant post-surgical improvement in motor speed, which was accompanied by a better quality of life and reduced symptoms of depression and anxiety. Conclusion PEA with repeated short periods of circulatory arrest in CTEPH did not result in any neuropsychological complications and may even lead to post-surgical psychological improvements. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of hypothermic neural rescue at birth on health-related quality of life (HRQL) in middle childhood.Design: Six-year to 7-year follow-up of surviving children from the Total Body Hypothermia for Neonatal Encephalopathy (TOBY) Trial.Setting: Community study including a single parental questionnaire to collect information on children's HRQL.Patients: 145 children (70 in the control group, 75 in the hypothermia group) whose parents consented and returned the questionnaire.Interventions: Intensive care with cooling of the body to 33.5°C for 72 hours or intensive care alone.Main Outcome Measures: HRQL attributes and utility scores using the Health Utilities Index (HUI).Results: At 6-7 years, speech appeared disproportionately affected when compared with other aspects of HRQL but levels of normal emotional functioning were similar in both groups. The mean (SE) HUI3 HRQL scores were 0.73 (0.05) in the hypothermia group and 0.62 (0.06) in the control group; mean difference (95% CI) 0.11 (-0.04 to 0.26).Conclusions: Findings of non-significant differences were not unexpected; the study used data from long-term survivors in a neonatal trial and was underpowered. However, results favoured moderate hypothermia and so complement the clinical results of the TOBY Children study. The work provides further insight into the long-term HRQL impact of perinatal asphyxial encephalopathy and provides previously unavailable utility data with which to contemplate the longer term cost-effectiveness of hypothermic neural rescue.Trial Registration Number: This study reports on the follow-up of the TOBY clinical trial: ClinicalTrials.gov number NCT01092637. [ABSTRACT FROM AUTHOR]

Acute cerebral infarction can progress rapidly, and there are limited specific and effective treatments. Small ubiquitin‑like modifiers (SUMOs) provide an important post‑translational modification of proteins. Following cerebral infarction, multiple proteins can combine with SUMOs to protect nerve cells. Furthermore, moderate hypothermia (core body temperature, 33‑34˚C) can increase the level of SUMOylation on multiple proteins. In the present study, it was examined whether moderate hypothermia increases the survival rate of bone marrow stromal stem cells (BMSCs) implanted in the cerebral ischemic penumbra via SUMOylation of multiple proteins. Firstly, BMSCs were exposed to oxygen‑glucose deprivation (OGD) under moderate hypothermic (33˚C) conditions. Subsequently, adult rats with middle cerebral artery occlusion were treated with a combination of BMSCs and moderate hypothermia (32‑34˚C). The results demonstrated that hypothermia promoted the combination of multiple proteins with SUMOs in BMSCs, and induced transport of SUMOs from the cytoplasm to the nucleus. Moderate hypothermia additionally reduced damage to BMSCs following OGD and improved BMSC survival following transplantation into the penumbra. These data suggest that moderate hypothermia may protect against BMSC injury via rapid SUMOylation of intracellular proteins. Thus, BMSC transplantation combined with moderate hypothermia may be a potential therapeutic strategy to treat cerebral infarction. [ABSTRACT FROM AUTHOR]

Background We analyzed our experience with the aortic arch operations performed through a minimally invasive approach, with emphasis on safety and feasibility, early and late outcomes. Material and methods We reviewed the medical records of 71 adult patients with aortic arch aneurysm (58, 82%), dissection (10, 14%) or porcelain aorta (3, 4%) who underwent primary arch surgery through a partial upper sternotomy. Results The aortic arch was replaced partially in 45 (63%), or totally in 26 (37%) patients. The repair was further extended with the elephant trunk procedure, conventional in 8 (11.3%) or frozen in 15 (21.1%) patients. No conversion to full sternotomy was needed. New permanent renal failure occurred in 1 (1.4%), temporary neurologic deficit in 2 (2.8%) and permanent neurologic deficit in 3 (4.2%) patients. Early mortality was observed in 4 (5.6%) patients. Actuarial survival was 79.2 ± 8.3% at 4 years and cumulative reoperation-free survival was 76.4 ± 9.4% at 4 years. Conclusion Minimally invasive aortic arch surgery is safe and feasible. Early outcomes are at the lower range compared to other published series. Late outcomes are not adversely influenced, as the desired extent of aortic resection can be achieved, producing a durable aortic repair. [ABSTRACT FROM AUTHOR]

Objective We examined the early outcomes and the long-term survival associated with different degrees of hypothermia in patients who received antegrade cerebral perfusion (ACP) for >30 minutes. Methods During a 10-year period, 544 consecutive patients underwent proximal and total aortic arch surgery and received ACP for >30 minutes and 1 of 3 levels of hypothermia: deep (14.1°C-20°C; n = 116 [21.3%]), low-moderate (20.1°C-23.9°C; n = 262 [48.2%]), and high-moderate (24°C-28°C; n = 166 [30.5%]). A variable called “predicted temperature” was used in propensity-score analysis. Multivariate analysis was done to evaluate the effect of actual temperature on outcomes. Results The operative mortality rate was 12.5% (n = 68) overall and was 15.5%, 11.8%, and 11.5% in the deep, low-moderate, and high-moderate hypothermia patients, respectively ( P = .54). The persistent stroke rate was 6.6% overall and 12.2%, 4.6%, and 6.0% in these 3 groups, respectively ( P = .024 on univariate analysis). On multivariate analysis, actual temperature was not associated with mortality, but lower temperatures predicted persistent stroke and reoperation for bleeding. In the propensity-matched subgroups, the patients with predicted deep hypothermia had (nonsignificantly) greater rates of persistent stroke (12.2% vs 4.9%; relative risk, 1.08; 95% CI, 0.87-1.15) and reoperation for bleeding (14.6% vs 2.4%; relative risk, 1.14; 95% CI, 0.87-1.15) than the patients with predicted moderate hypothermia. On long-term follow-up (mean duration, 5.12 years), 4- and 8-year survival rates were 62.3% and 55.7% in the deep hypothermia group and 75.4% and 74.2% in the moderate hypothermia group ( P = .0015). Conclusions In proximal and arch operations involving ACP for >30 minutes, greater actual temperatures were associated with less stroke and reoperation for bleeding. There were no significant differences among the predicted hypothermia levels, although a trend toward a higher rate of adverse events was noticed in the deep hypothermia group. Long-term survival was better in the moderate hypothermia group. [ABSTRACT FROM AUTHOR]