Selective Cerebral Hypothermia Research Articles

Selective-cerebral-hypothermia-induced neuroprotection against-focal cerebral ischemia/reperfusion injury is associated with an increase in SUMO2/3 conjugation

Selective cerebral hypothermia is considered an effective treatment for neuronal injury after stroke and avoids the complications of general hypothermia. Several recent studies hanve suggested that SUMO2/3 conjugation occurs following cerebral ischemia/reperfusion (I/R) injury. However, the relationship between the cerebral protective effect of selective cerebral hypothermia and SUMO2/3 conjugation remains unclear. In this study, we investigated the effect of selective cerebral hypothermia on SUMO2/3 conjugation during focal cerebral I/R injury. A total of 140 Sprague-Dawley rats were divided into four groups. In the sham group, only the carotid artery was exposed. The endoluminal filament technique was used to induce middle cerebral artery occlusion in the other three groups. After 2 h of occlusion, the filaments were slowly removed to allow blood reperfusion in the I/R group. In the hypothermia (HT) group and normothermia (NT) group, normal saline at 4 °C and 37 °C, respectively , was perfused through the carotid artery, followed by the restoration of blood flow. The results of the modified neurological severity score (mNSS), 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (HE) staining, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining demonstrated that selective cerebral hypothermia significantly decreased I/R-induced neuronal injury (mNSS, n = 8, 24 h, HT (5.88 ± 2.36) vs. I/R (8.63 ± 3.38), P < 0.05. 48 h, HT (5.75 ± 2.25) vs. I/R (8.5 ± 2.88), P < 0.05. Cerebral infarct volume percentages, n = 5, HT (18.71 ± 2.13) vs. I/R (41.52 ± 2.90), P < 0.01. Cell apoptosis rate, n = 5, 24 h, HT (21.28 ± 2.61) vs. I/R (43.72 ± 4.30), P < 0.05. 48 h, HT (20.50 ± 2.53) vs. I/R (38.94 ± 2.93), P < 0.05). The expression of Ubc9 and conjugated SUMO2/3 proteins was increased at 24 and 48 h after reperfusion in the 3 non-sham groups, and hypothermia further upregulated the expression of Ubc9 and conjugated SUMO2/3 proteins in the HT group. The expression of SENP3 was increased in the NT group and I/R group, while it was decreased in the HT group at 24 and 48 h after reperfusion (Relative quantities, n = 5, Ubc9, 24 h, HT (2.44 ± 0.22) vs. I/R (1.55 ± 0.39), P < 0.05. 48 h, HT (2.69 ± 0.16) vs. I/R (2.25 ± 0.33), P < 0.05. SENP3, 24 h, HT (0.47 ± 0.15) vs. I/R (2.18 ± 0.43), P < 0.05. 48 h, HT (0.72 ± 0.06) vs. I/R (1.51 ± 0.19), P < 0.05. conjugated SUMO2/3 proteins, 24 h, HT (2.84 ± 0.24) vs. I/R (2.51 ± 0.20), P < 0.05. 48 h, HT (2.73 ± 0.13) vs. I/R (2.44 ± 0.13), P < 0.05). Further analysis showed that the variation in SENP3 expression was more obvious than that in Ubc9 under hypothermia intervention in the HT group. These findings suggest that selective cerebral hypothermia could increase SUMO2/3 modification mainly via down-regulating the expression of SENP3, and then exert neuroprotective effects in rats with cerebral I/R injury.

Effects of selective intracarotid cerebral hypothermia on the size of ischaemic stroke in an experiment

Background. Ischaemic stroke is one of the leading causes of death and disability worldwide. Selective intracarotid cerebral hypothermia is one of the promising methods to prevent ischaemic stroke. However, currently available studies do not allow us to conclude the effectiveness of applying this method in humans and assess its effect on the system temperature.Aim. To investigate the effect of selective intracarotid cerebral hypothermia on the size of ischaemic stroke in large pigs, determining the optimal period of hypothermia and the severity of the effects of intracarotid hypothermia on the system temperature.Methods. The study was conducted on mini-pigs weighing 30–70 kg and included two stages. During the first stage, pigs were divided into two groups: control (n = 4) and intracarotid hypothermia for 3 h, exciting periods before and after reperfusion (n = 2). During the second stage, animals were also divided into two groups: hypothermia group within 1.5 h before reperfusion (n = 2) and hypothermia group within 1.5 h after reperfusion (n = 2). The technique for modelling ischaemic stroke was the same as in all groups and consisted of frontotemporal craniotomy and compression of the middle cerebral artery for 3 h. Intracarotid hypothermia was performed by infusing + 4 °C NaCl solution in the ascending pharyngeal artery. At 48 h after starting the experiment, a brain magnetic resonance imaging scan was performed to determine the size of the stroke.Results. The mean size of the stroke focusing in the control group was 10.75%, in the hypothermia group before reperfusion (10.95%) and in the hypothermia group after reperfusion (1.65%) of the volume of the cerebral hemisphere. The stroke size in the hypothermia group for 3 h could not be determined due to complications that developed in animals intraoperatively and postoperatively. The effect of intracarotid hypothermia on the systemic temperature in an animal weighing 65 kg was 0.4 °C.Conclusion. Based on the study results, a marked decrease in the focus of ischaemic stroke was found with the use of intracarotid hypothermia within 1.5 h after reperfusion. Intracarotid hypothermia was found to do not have a pronounced effect on the system temperature. Received 2 May 2020. Revised 20 May 2020. Accepted 25 May 2020. Funding: The work is supported by a grant of the Russian Foundation for Basic Research (project No. 18-415-540025). Conflict of interest: Authors declare no conflict of interest. Author contributionsConception and study design: E.I. Fartakov, V.V. Lomivorotov, E.I. Kretov, A.R. TarkovaData collection and analysis: D.U. Malaev, A.A. Boykov, A.A. Prokhorikhin, D.V. Volchenko, I.S. Zykov, P.O. SeleznevDrafting the article: E.I. Fartakov, D.U. Malaev, A.R. TarkovaCritical revision of the article: E.I. Kretov, V.V. Lomivorotov, V.I. Baystrukov, N.I. Grachev, D.S. Sergeevichev, A.M. ChernyavskiyFinal approval of the version to be published: E.I. Fartakov, V.V. Lomivorotov, D.U. Malaev, A.R. Tarkova, A.A. Boykov, A.A. Prokhorikhin, D.V. Volchenko, I.S. Zykov, P.O. Seleznev, V.I. Baystrukov, N.I. Grachev, D.S. Sergeevichev, A.M. Chernyavskiy, E.I. Kretov

Effects of selective brain hypothermia on expression of miR-484 during cerebral ischemia-reperfusion in rats

Objective To evaluate the effects of selective brain hypothermia on the expression of miR-484 during cerebral ischemia-reperfusion (I/R) in rats. Methods A total of 120 clean-grade healthy male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were divided into 4 groups (n=30 each) using a random number table method: sham operation group (group S), cerebral I/R group (group I/R), hypothermia group (group H) and normothermia group (group N). Blood vessels were only separated and ligated without blockade in group S. In the other three groups, cerebral I/R was induced by inserting a nylon thread with rounded tip into the right internal carotid artery, and the middle cerebral artery was occluded for 2 h followed by reperfusion.In group H, 4 ℃ normal saline was infused for 15 min at a rate of 80 ml·kg-1·h-1 through the internal carotid artery immediately after removing the nylon thread.In group N, 37 ℃ normal saline was infused in the same way.Neurological deficit scores were evaluated at 6, 24 and 48 h after reperfusion.Animals were then sacrificed, the cerebral cortex of the ischemic penumbra was removed for determination of nerve cell apoptosis (by TUNEL method), expression of mitochondrial fission protein 1 (Fis1) (by Western blot) and expression of miR-484 (quantitative real-time polymerase chain reaction). The apoptotic rate was calculated. Results Compared with group S, the neurological deficit score and apoptotic rate of nerve cells were significantly increased, and the expression of Fis1 was up-regulated at each time point in the other three groups, the expression of miR-484 was significantly down-regulated in I/R and N groups, and the expression of miR-484 was significantly up-regulated in group H (P<0.05 or 0.01). Compared with group I/R and group N, the neurological deficit score and apoptotic rate of nerve cells were significantly decreased, and the expression of Fis1 was down-regulated, and the expression of miR-484 was up-regulated at each time point in group H (P<0.05 or 0.01). Conclusion The mechanism by which selective cerebral hypothermia attenuates cerebral I/R injury is associated with up-regulating miR-484 expression and thus down-regulating Fis1 expression in rats. Key words: Hypothermia; Brain; Reperfusion injury; MicroRNAs

Possibilities and prospects of hypothermia in the treatment of ischemic stroke

Today the Russian Federation has one of the worst indicators in the world in terms of morbidity and mortality from stroke. Currently, two methods are used to treat ischemic stroke: thrombolysis and thrombextraction. However, despite their effectiveness, the methods have limited use due to the presence of strict indications and contraindications. In this regard, the search for new methods of treating ischemic stroke, which can be effective both with independent use and as an addition to already existing methods, is an urgent task. The purpose of this paper is to review research studies on the use of hypothermia in ischemic stroke. Hypothermia has a proven neuroprotective effect in cerebral ischemia. In this context, interest is the method of intracarotid selective cerebral hypothermia, which, according to a number of preclinical studies, significantly reduces the volume of cerebral infarction after ischemic stroke. The advantage of this method is the rapid achievement of the target temperature, a targeted effect on the brain and a minimal effect on the system temperature. Thus, intracarotid selective cerebral hypothermia is a very promising method for the treatment of ischemic stroke and deserves further study. In this regard, the authors decided to conduct a preclinical study on this subject. Received 9 October 2018. Revised 25 January 2019. Accepted 30 January 2019. Published online 11 March 2019. Funding: The work was funded by the Russian Foundation for Basic Research (grant No. 18-415-540025). Conflict of interest: Authors declare no conflict of interest. ORCID IDE.I. Fartakov, https://orcid.org/0000-0002-1847-7291A.R. Tarkova, http://orcid.org/0000-0002-4291-6047E.I. Kretov, http://orcid.org/0000-0002-7109-9074V.V. Lomivorotov, https://orcid.org/0000-0001-8591-6461I.S. Zykov, http://orcid.org/0000-0001-6253-9026

Study on selective cerebral hypothermia protection by carotid perfusion

Therapeutic hypothermia is known as an effective method for cerebral protection. However, its application is limited due to the complications of whole body hypothermia and low effectiveness of ice blankets and caps. Recently, internal carotid artery perfusion has drawn considerable attentions with the advantages of high effectiveness, long maintenance time, blood dilution and fleshing of inflammatory mediators. This article reviewed the principle, methods and advantages of carotid selective brain cooling, discuss carotid infusion for selective brain cooling in recent study, so as to provide more safely and reliable methods for cerebral protection and improve long-term quality of life. Key words: Intracarotid perfusion; Hypothermia; Cerebral protection

Influence of selective cerebral hypothermia on resting energy expenditure in patients in acute period of ischemic stroke

Influence of selective cerebral hypothermia on resting energy expenditure in patients in acute period of ischemic stroke

Total arch repair with open placement of a novel double-branched stent graft for acute Type A aortic dissection: a single-centre experience with 21 consecutive patients

The aim of this study was to evaluate the safety and feasibility of total arch repair with open placement of a novel double-branched stent graft for acute Type A aortic dissection (TAAD). We retrospectively analysed the effect of the double-branched stent graft for total aortic arch placement with acute TAAD from December 2013 to February 2015. The effectiveness of the open placement of the double-branched stent graft was estimated by complete thrombus obliteration of the false lumen surrounding it on computed tomography angiography. Follow-up was performed at 6 months postoperatively and annually thereafter. The double-branched stent graft was successfully placed into the true lumen of the descending aorta, aortic arch, left subclavian artery and left common carotid artery through the delivery system in 21 patients with acute TAAD. The mean cardiopulmonary bypass time was 210.2 ± 32.4 min, the mean aortic cross-clamp time was 94.9 ± 18.0 min, and the selective cerebral perfusion and deep hypothermia cardiopulmonary arrest time was 27.0 ± 10.4 min. The in-hospital mortality rate was 4.8%. The mean follow-up duration was 38.2 ± 12.5 months. No severe complications related to the surgery or residual dissection occurred during the follow-up. All survivors resumed normal activities. The novel double-branched stent graft is proved to be safe and effective for total arch repair with acute TAAD in this study. It would be a new selective method for total arch repair in patients with acute TAAD. Research on pathogenic risk factors or characteristic features and clinical treatment of aortic dissection in Chinese Population (20120216-4).

P507Endovascular selective cerebral hypothermia; experimental in vivo studies and initial clinical experience

P507Endovascular selective cerebral hypothermia; experimental in vivo studies and initial clinical experience

Local cerebral hypothermia induced by selective infusion of cold lactated ringer’s: a feasibility study in rhesus monkeys

Background and Objective: Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer’s solution in rhesus monkeys.Methods: Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer’s solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls.Results: Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR.Conclusion: Local infusion of ice-cold lactated Ringer’s solution via micro-catheter is a safe and effective method for selective cerebral hypothermia. This cooling method could potentially be developed as a new treatment in acute ischemic stroke.

Endovascular Cooling Catheter for Selective Brain Hypothermia: An Animal Feasibility Study of Cooling Performance

Therapeutic hypothermia represents a promising neuroprotective treatment in acute ischemic stroke. Selective cerebral hypothermia applied early, prior to and during endovascular mechanical recanalization therapy, may be beneficial in the critical phase of reperfusion. We aimed to assess the feasibility of a new intracarotid cooling catheter in an animal model. Nine adult sheep were included. Temperature probes were introduced into the frontal and temporal brain cortices bilaterally. The cooling catheter system was introduced into a common carotid artery. Selective blood cooling was applied for 180 minutes. Systemic and local brain temperatures were measured during cooling and rewarming. Common carotid artery diameters and flow were measured angiographically and by Doppler sonography. The common carotid artery diameter was between 6.7 and 7.3 mm. Common carotid artery blood flow velocities increased moderately during cooling and after catheter removal. Maximum cerebral cooling in the ipsilateral temporal cortex was -4.7°C (95% CI, -5.1 to -4.0°C). Ipsilateral brain temperatures dropped significantly faster and became lower compared with the contralateral cortex with maximum temperature difference of -1.3°C (95% CI, -1.5 to -1.0°C; P < .0001) and compared with systemic temperature (-1.4°C; 95% CI, -1.7 to -1.0°C; P < .0001). Sheep proved a feasible animal model for the intracarotid cooling catheter. Fast induction of selective mild hypothermia was achieved within the cooled cerebral hemisphere, with stable temperature gradients in the contralateral brain and systemic blood. Further studies are required to demonstrate any therapeutic benefit of selective cerebral cooling in a stroke model.

Combined Selective Cerebral Hypothermia and Mechanical Artery Recanalization in Acute Ischemic Stroke: In Vitro Study of Cooling Performance.

Therapeutic hypothermia represents a promising neuroprotective treatment for patients with ischemic stroke. Selective, intracarotid blood cooling may initiate rapid and early brain hypothermia, reduce systemic effects, and allow combined endovascular mechanical thrombectomy. For this approach, a balloon cooling catheter system was designed and studied in vitro to optimize its cooling performance. Computational fluid dynamics of blood cooling was performed within the common carotid artery lumen by using 3 different catheter designs (1-, 2-, and 4-balloon array). On the basis of these results, a first catheter prototype was manufactured, and its heat-exchange performance was tested in an artificial in vitro circulation simulating the common carotid artery lumen at different flow rates (inflow temperature of 37°C). In the computational fluid dynamics model, the catheter with the 4-balloon array achieved the highest cooling rate of -1.6°C, which may be attributed to disruption of the thermal boundary layers. In the in vitro study, cooling of the blood substitute at flow rates of 400 mL/min (normal common carotid artery flow) and 250 mL/min (reduced common carotid artery flow due to distal MCA occlusion) achieved a temperature drop inside the blood substitute along the cooling balloons of -1.6°C and -2.2°C, respectively. The feasibility of intracarotid blood cooling using a new catheter system was demonstrated in vitro. A serial 4-balloon array led to an optimized cooling capacity approaching optimum target temperatures of mild therapeutic hypothermia. To determine the therapeutic efficacy of combined selective therapeutic hypothermia and mechanical thrombectomy, further in vivo studies by using a model of temporary ischemia with large-vessel occlusion and recanalization are required.

Changes in hippocampal ultrastructure and vimentin expression in rhesus monkeys following selective deep hypothermia and blood occlusion.

Previous studies have shown that selective cerebral profound hypothermia combined with antegrade cerebral perfusion can improve resistance to cerebral hypoxia-ischemia in monkeys. The aim of this study was to observe the effect of selective cerebral profound hypothermia on the ultrastructure and vimentin expression in monkey hippocampi after severe cerebral ischemia. Eight healthy adult rhesus monkeys were randomly divided into two groups: profound hypothermia (N = 5) and normothermia (N = 3). Monkeys in the profound hypothermia group underwent bilateral carotid artery and jugular vein occlusion for 10 minutes at room temperature. Ringer's solution at 4°C was then perfused through the right internal carotid artery and out of the right jugular vein, maintaining the brain temperature below 18°C. Sixty minutes later, cerebral blood flow was restored. The normothermia group underwent all procedures with the exception that the Ringer's solution was 37°C during perfusion. All animals in the profound hypothermia group were successfully resuscitated. No significant abnormalities of hippocampal morphology or ultrastructure were observed. In contrast, no monkeys were alive after perfusion in the normothermia group and they had abnormal hippocampal morphology and ultrastructure to different extents. Vimentin expression in the hippocampus was significantly lower in the profound hypothermia group (47.88% ± 1.66) than the normothermia group (79.51% ± 1.00; P < 0.01). We conclude that selective cerebral profound hypothermia following 10-min occlusion of the bilateral common carotid arteries was able to downregulate vimentin expression in the hippocampus and protect it from severe cerebral ischemia.

¹H-MRS before and after resuscitation following selective cerebral ultra-profound hypothermic blood flow occlusion in monkeys.

We investigated the effect of selective cerebral ultra-profound hypothermic blood flow occlusion on brain tissue and cell metabolism to ascertain the efficacy and safety of selective deep hypothermic technologies using proton magnetic resonance spectroscopy ((1)H-MRS). The bilateral carotid artery was blocked at room temperature for 10 min. Other neck vessels were then blocked through cold perfusion of the internal carotid artery and reflux of the ipsilateral jugular vein. Thus, selective cerebral extracorporeal circulation was established. Brain temperature was reduced to 15.1° ± 0.9°C. After 60 min, cerebral blood flow recovered naturally. Routine magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and (1)H-MRS examination of the bilateral frontal cortex and basal ganglia were performed prior to surgery and 4, 24, 72 h, 21 days after recovery. The formants and areas under the curve (AUC) of N-acetyl aspartate (NAA), choline (Cho), creatine/phosphocreatine (Cr/Cr2) were analyzed using 1H-MRS. The pre- and postoperative AUC of NAA and Cho at different time points were compared. Conventional MRI and DWI showed no abnormal signal changes in the brain parenchyma or right basal ganglia before and after surgery (P > 0.05). There was no significant difference in the ratio between NAA/(Cr+Cr2) and Cho/(Cr+Cr2) before and after surgery in the bilateral basal ganglia and frontoparietal regions of the cortex (P > 0.05). Quantitative (1)H-MRS showed that selective deep cerebral hypothermia significantly improved the brain's tolerance to ischemia and hypoxia. Our results could provide a better understanding of the efficacy and safety of selective deep hypothermia and blood flow occlusion.

EEG asymmetry during aortic arch surgeries associated with selective preferential cerebral hypothermia.

Intraoperative EEG monitoring is increasingly used during aortic arch procedures for early detection of acute neurologic dysfunction. In those procedures involving cardiopulmonary bypass, increased neuroprotection may be gained by using hypothermic circulatory arrest and selective cerebral perfusion. Several techniques for cerebral perfusion exist; yet no studies have noted distinct EEG patterns associated with different techniques. In this study, we reviewed EEG records of six aortic arch procedures that used cannulation of the innominate artery to provide selective antegrade cerebral perfusion. In each case, a transient hemispheric asymmetry was noted within 2 minutes of the start of head cooling, consisting of enhanced suppression over the right compared with the left hemisphere, which was confirmed by power analysis. The EEG returned to baseline during passive-head rewarming in five cases, whereas a brief left-sided partial seizure occurred during rewarming in one case. These findings suggest that antegrade cerebral perfusion using cannulation of the innominate artery results in enhanced cooling of the right hemisphere as detected by intraoperative EEG monitoring. Characterization of this finding is necessary to prevent misinterpretation of ischemia by EEG.

Selective cerebral hypothermia induced via hypothermic retrograde jugular vein saline flush in a porcine model

Objectives:Multiple methods of selective brain cooling have been used to prevent cerebral ischemia secondary to trauma and pathological or iatrogenic cerebral blood flow restriction. In this study, we tested the efficacy of hypothermic retrograde jugular vein flush (HRJVF) in eliciting selective brain hypothermia in a porcine model.Methods:Twelve swine were divided into two groups: retrograde jugular vein infusion (RJVI) with cold saline (4°C RJVI, n = 6) and with room temperature saline (24°C RJVI, n = 6). For 90 minutes, the following parameters were measured: brain parenchymal temperature, rectal temperature, intracranial pressure (ICP), mean arterial pressure, and heart rate (HR).Results:Swine receiving 4°C RJVI experienced a drop in mean brain parenchymal temperature of 1·1 ± 0·1°C, compared to 0·1 ± 0·1°C in swine receiving 24°C RJVI. At 90 minutes, mean brain parenchymal temperature in the 4°C RJVI treatment group was 35·5 ± 0·2°C, as compared to 37·1 ± 0·2°C in the 24°C RJVI treatment group (P < 0·001). In the 4°C RJVI group, the brain-systemic temperature gradient peaked 10 minutes after initiation of cooling and remained significantly different when comparing the two experimental groups (P < 0·001) throughout the duration of the 90 minutes experiment. Of note, ICP, mean arterial pressure, and HR remained constant without any significant changes or differences between treatment groups.Discussion:These results suggest that HRJVF is an effective method for selective brain hypothermia in a large animal model. Clinical application may prove effective in delaying neural ischemia.

Sonographic and MRI findings in neonates following selective cerebral hypothermia.

Hypoxic ischemic insults during labor remain an important cause of brain injury in term and near-term neonates. Selective cerebral hypothermia is a potentially neuroprotective rescue therapy. Ultrasonography (US) and magnetic resonance imaging (MRI) are routinely used to visualize intracranial changes in neonatal hypoxic-ischemic injuries. We attempted to describe all pathological findings on US and MRI in the brains of our patients following selective cerebral hypothermia. Twenty-nine neonates with hypoxic-ischemic encephalopathy (HIE) following therapeutic cooling were assessed with cranial ultrasound (US) and magnetic resonance imaging (MRI). The findings were compared with the clinical outcome. Over one-fourth (27.6%) of the examined infants had a normal brain on MRI (with only 17.2% on US). Involvement of the basal ganglia and thalami was one of the most frequent findings in our material (9/29 = 31% on MRI, and 7/29-24.1% on US). Cerebral parenchymal hemorrhage was detected on MRI in as many as 7 (24.1%) and cerebellar parenchymal hemorrhage in 4 (13.8%) infants. The loss in the gray-white matter differentiation ('fuzzy brain'), usually transient on US, was observed in 79.3% of the neonates. Diffusion restriction in the callosal splenium (13.8%) and hyperechoic thalami and basal ganglia were strictly correlated to a significantly higher incidence of severe developmental delay. Abnormalities on MRI and US were observed in 75% of newborns with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia.

Successful Repair of a Syphilitic Aortic Arch Aneurysm Accompanied by Serious Cerebral Infarction

We present a 52-year-old male with a syphilitic aortic arch aneurysm accompanied by relevant extensive cerebral infarction. He was admitted to a local hospital for sudden loss of consciousness, where he was diagnosed with serious cerebral infarction. During his treatment, a multilocular aortic arch aneurysm involving the arch vessels was found incidentally. He was transferred to our hospital for surgical treatment. A preoperative routine laboratory test for syphilis was highly positive, which suggested that the aneurysm was likely caused by syphilis and the cerebral infarction was also induced by the involvement of syphilitic aortitis or arteritis. After 2 weeks of antibiotic therapy for syphilis, total arch replacement was performed successfully using meticulous brain protection with antegrade selective cerebral perfusion and deep hypothermia. He recovered without any further cerebral deficits. The pathological examination of the surgical specimen showed some characteristic changes of syphilitic aortitis.

Introduction to a Norwood Program in an Emerging Economy: Learning Curve of a Single Center

There has been a notable improvement in the outcome of stage 1 palliation for hypoplastic left heart syndrome (HLHS) in recent years. Nevertheless, developing a new Norwood program requires a steep learning curve, especially in emerging economies where rapid population growth brings a high volume of patients but, on the other hand, resources are limited. In this paper we aimed to summarize the initial results of a single center. Hospital records of 21 patients were reviewed for all patients having a stage 1 palliation procedure for HLHS between May 2011 and May 2013. There were 13 male (62%) and 8 female (38%) patients. Median age was 14 days (range, 4-74 days) and median weight was 3030 g (2600-3900 g). HLHS was defined as mitral or aortic stenosis or atresia (or both) in the presence of normally related great vessels and a hypoplastic left ventricle. Transthoracic echocardiography was the diagnostic modality used in all patients. All procedures but one were performed using an antegrade selective cerebral perfusion method and moderate hypothermia. Cerebral perfusion was monitored with cerebral oximetry in all patients. Modified ultrafiltration was routinely used in all patients. Overall hospital mortality was 47.6% (n = 10). Mortality rates considerably decreased from the first year to second year (69% and 12.5% respectively). No risk factors were identified for mortality. Surgical palliation of neonates with hypoplastic left heart syndrome continues to be a challenge. To decrease the overall mortality nationwide and improve outcomes, a referral center with a dedicated team is necessary in emerging economies.

Chirurgie der Aorta ascendens und des Aortenbogens

The surgical therapy of the ascending aorta and the aortic arch with its supraarotic branches has been, and still is, one of the major challenges in the therapy of the aorta. There have been major developments in the endovascular therapy field, which can be used as a complementary or even sometimes as an alternative to the standard surgery. Therefore, an interdisciplinary approach is a prerequisite for optimal therapy planning for such patients. The risk of operating under circulatory arrest has been markedly reduced due to the continued development of cardiosurgical techniques, especially selective cerebral perfusion and mild hypothermia. Further developments of the therapy of aortic diseases via alternative approaches are expected in the near future. However, the conventional surgical therapy for pathologies in the ascending aorta (with/out the aortic valve) and the aortic arch is still the gold standard.

Excitatory amino acid changes in the brains of rhesus monkeys following selective cerebral deep hypothermia and blood flow occlusion.

Selective cerebral deep hypothermia and blood flow occlusion can enhance brain tolerance to ischemia and hypoxia and reduce cardiopulmonary complications in monkeys. Excitotoxicity induced by the release of a large amount of excitatory amino acids after cerebral ischemia is the major mechanism underlying ischemic brain injury and nerve cell death. In the present study, we used selective cerebral deep hypothermia and blood flow occlusion to block the bilateral common carotid arteries and/or bilateral vertebral arteries in rhesus monkey, followed by reperfusion using Ringer’s solution at 4°C. Microdialysis and transmission electron microscope results showed that selective cerebral deep hypothermia and blood flow occlusion inhibited the release of glutamic acid into the extracellular fluid in the brain frontal lobe and relieved pathological injury in terms of the ultrastructure of brain tissues after severe cerebral ischemia. These findings indicate that cerebral deep hypothermia and blood flow occlusion can inhibit cytotoxic effects and attenuate ischemic/hypoxic brain injury through decreasing the release of excitatory amino acids, such as glutamic acid.