During Deep Hypothermic Circulatory Arrest Research Articles

CIRP attenuates acute kidney injury after hypothermic cardiovascular surgery by inhibiting PHD3/HIF-1α-mediated ROS-TGF-β1/p38 MAPK activation and mitochondrial apoptotic pathways

BackgroundThe ischemia–reperfusion (IR) environment during deep hypothermic circulatory arrest (DHCA) cardiovascular surgery is a major cause of acute kidney injury (AKI), which lacks preventive measure and treatment. It was reported that cold inducible RNA-binding protein (CIRP) can be induced under hypoxic and hypothermic stress and may have a protective effect on multiple organs. The purpose of this study was to investigate whether CIRP could exert renoprotective effect during hypothermic IR and the potential mechanisms.MethodsUtilizing RNA-sequencing, we compared the differences in gene expression between Cirp knockout rats and wild-type rats after DHCA and screened the possible mechanisms. Then, we established the hypothermic oxygen–glucose deprivation (OGD) model using HK-2 cells transfected with siRNA to verify the downstream pathways and explore potential pharmacological approach. The effects of CIRP and enarodustat (JTZ-951) on renal IR injury (IRI) were investigated in vivo and in vitro using multiple levels of pathological and molecular biological experiments.ResultsWe discovered that Cirp knockout significantly upregulated rat Phd3 expression, which is the key regulator of HIF-1α, thereby inhibiting HIF-1α after DHCA. In addition, deletion of Cirp in rat model promoted apoptosis and aggravated renal injury by reactive oxygen species (ROS) accumulation and significant activation of the TGF-β1/p38 MAPK inflammatory pathway. Then, based on the HK-2 cell model of hypothermic OGD, we found that CIRP silencing significantly stimulated the expression of the TGF-β1/p38 MAPK inflammatory pathway by activating the PHD3/HIF-1α axis, and induced more severe apoptosis through the mitochondrial cytochrome c-Apaf-1-caspase 9 and FADD-caspase 8 death receptor pathways compared with untransfected cells. However, silencing PHD3 remarkably activated the expression of HIF-1α and alleviated the apoptosis of HK-2 cells in hypothermic OGD. On this basis, by pretreating HK-2 and rats with enarodustat, a novel HIF-1α stabilizer, we found that enarodustat significantly mitigated renal cellular apoptosis under hypothermic IR and reversed the aggravated IRI induced by CIRP defect, both in vitro and in vivo.ConclusionOur findings indicated that CIRP may confer renoprotection against hypothermic IRI by suppressing PHD3/HIF-1α-mediated apoptosis. PHD3 inhibitors and HIF-1α stabilizers may have clinical value in renal IRI.

Renal cell carcinoma with intracardiac tumor thrombus extension: Radical surgery yields 2 years of postoperative survival in a single-center study over a period of 30 years.

Renal cell carcinoma (RCC) with tumor thrombus extension into the right atrium (level IV) is a rare life-threatening clinical condition that can only be managed by means of a combined urological and cardiac surgical approach. The early and late outcomes of this radical treatment were analyzed in a large single-institution series over a period of 30 years. In 37 patients with RCC and intracardiac tumor thrombus extension, nephrectomy was performed followed by the extraction of the intracaval and intracardiac tumor thrombus under direct visual control during deep hypothermic circulatory arrest (DHCA). Recently, in 13 patients, selective aortic arch perfusion (SAAP) was instituted during DHCA. In all patients, precise removal of the tumor thrombus was accomplished in a bloodless field. The mean duration of isolated DHCA was 15 ± 6min, and 31.5 ± 10.2min in the case of DHCA + SAAP, at a mean hypothermia of 22.7 ± 4°C. In-hospital mortality was 7.9% (3 patients). In Kaplan-Meier analysis, the estimated median survival was 26.4 months whereas the 5-year cancer-related survival rate was 51%. Despite its complexity, this extensive procedure can be performed safely with a generally uneventful postoperative course. The use of cardiopulmonary bypass with DHCA, with the advantage of SAAP, allows for a safe, precise, and complete extirpation of intracaval and intracardiac tumor mass. Late outcomes after radical surgical treatment in patients with RCC and tumor thrombus reaching up in the right atrium in our series justify this extensive procedure.

Correlation between cerebral oxygen saturation monitored by near-infrared spectroscopy during operation and risk of stroke after acute type A aortic dissection surgery

Objective: Near-infrared spectroscopy (NIRS) is widely used for intraoperative cerebral oxygen saturation monitoring in patients with acute type A aortic dissection. This study aimed to investigate the correlation between NIRS-derived oxygen saturation and risk of postoperative stroke. Methods: This study included 193 patients with acute type A aortic dissection undergoing emergency surgery and elective unilateral cerebral perfusion via the right axillary artery at the Department of Cardiothoracic Surgery, Nanjing Drum Tower Hospital, Nanjing, China, from 2018 to 2020. NIRS was used for intraoperative cerebral oxygen saturation monitoring, and the basal values and the lowest values of cerebral oxygen saturation during deep hypothermic circulatory arrest (DHCA) were recorded. The patients were divided into no-stroke group (n=178, 92.2%) and stroke group (n=15, 7.8%) according to the absence or presence of postoperative stroke. The differences in preoperative, operative and postoperative clinical differences between the two groups were compared, and the relationship between the lowest cerebral oxygen saturation value and the change in cerebral oxygen saturation value ((base-lowest)/basal) and postoperative stroke were analyzed. Results: The proportion of preoperative atrial fibrillation (6.7% vs. 0.6%, P=0.026), and the proportion of preoperative hypotension (26.7% vs. 9.0%, P=0.031) were significantly higher in the stroke group than no-stroke group. There were no differences in the surgical approach between the two groups. Cardiopulmonary bypass (CPB) time ((256.1±84.8) h vs.(217.8±58.4) h, P=0.020), postoperative mechanical ventilation time ((139.3±172.8) h vs. (35.6±45.6) h, P<0.001) were significantly longer in stroke group as compared to no-stroke group. Incidence of postoperative tracheotomy (20.0% vs. 1.1%, P<0.001), acute kidney injury (73.3% vs. 30.3%, P=0.001) and continuous renal replacement therapy (46.7% vs. 11.8%, P<0.001) as well as mortality (20.0% vs. 5.1%, P=0.022) were significantly higher in the stroke group than in non-stroke group. There was no significant difference in the basal NIRS value and the lowest NIRS value during DHCA between the two groups. Patients in the stroke group had a significantly greater intraoperative change rate of right NIRS as compared to no-stroke group (15.2%±15.7% vs. 9.2%±7.0%, P=0.006). Conclusions: NIRS is valuable for monitoring cerebral oxygen saturation during acute type A aortic dissection surgery, and the rate change of NIRS during operation correlates significantly with postoperative stroke.

Cold-inducible RNA-binding protein maintains intestinal barrier during deep hypothermic circulatory arrest.

The intestinal injury during deep hypothermic circulatory arrest (DHCA) is harmful to clinical outcomes. Cold-inducible RNA-binding protein (CIRBP) plays a protective role in hypothermia. The aim of this study was to explore the effects of CIRBP on intestinal barrier during DHCA. Sprague-Dawley (wild type, n = 13) and knockout of Cirbp (Cirbp-/-, n = 8) rats were used in the model of DHCA. The histomorphology of the epithelial barrier was evaluated by haematoxylin-eosin, Chiu's scores, Gram's stain and Ki67. The function of the intestinal barrier was evaluated by serum intestinal fatty acid-binding protein, diamine oxidase and d-lactate. The structure of the epithelial barrier, phosphocreatine-creatine kinase system and adenosine triphosphate were assessed in the intestine. The expression of CIRBP significantly increased in the intestine during DHCA. Cirbp-/- rats showed obvious destruction of intestinal barrier after DHCA. Chiu's scores, intestinal fatty acid-binding protein, diamine oxidase and d-lactate significantly increased in the Cirbp-/- group. Ki67 showed that cell proliferation decreased in the Cirbp-/- rats. In the Cirbp-/- group, zonula occludens-1, E-cadherin and occludin levels were significantly decreased, and these proteins either disappeared or redistributed in the monolayer. Besides, Cirbp-/- resulted in decreased levels of creatine kinase B, glycine amidinotransferase, adenosine triphosphate and creatine contents in the intestine, affecting energy metabolism and balance, which is associated with the maintenance of epithelial barrier during acute injury. CIRBP is related to the maintenance of the intestinal epithelial barrier during DHCA, which is expected to be a new target for the prevention of intestinal injury.

Retrograde perfusion through superior vena cava reaches the brain during circulatory arrest.

The optimal technique for brain perfusion during circulatory arrest remains controversial. Concern exists that retrograde cerebral perfusion (RCP) via the superior vena cava (SVC) is unable to perfuse the brain. We evaluated whether RCP blood circulates through the brain parenchyma in humans during deep hypothermic circulatory arrest (DHCA). We hypothesized that a significant difference in the levels of S-100β (a protein with very high neuro-sensitivity) between the blood infused in the SVC and the effluent blood returning in the left carotid artery (CA) during RCP, should be regarded as a sign of the circulation of RCP blood through the brain parenchyma. We enrolled 10 non-consecutive patients undergoing elective arch-surgery using DHCA and RCP. Circulating S-100β levels were measured at baseline and immediately before DHCA. During DHCA and RCP the difference in S-100β between the SVC and the CA was evaluated after 10 minutes of arrest and immediately before resumption of the circulation. S-100β levels were evaluated using enzyme-linked immunosorbent assay (ELISA). Mean DHCA duration was 22.4±7.9 minutes. Mean S-100β level at baseline was 92.5±54.9 µg/L. After 10 minutes of DHCA the level of S-100β in the CA was significantly higher than in the SVC (936.9±326.3 vs. 810.9±307.4 µg/L, P=0.0021). This difference was enhanced at the second DHCA sample (1113.8±334.2 vs. 920.5±340.0 µg/L, P=0.0002). There was a statistically significant correlation between the duration of DHCA and the percent difference in S-100β level between the SVC and the CA (Pearson's correlation coefficient =0.902). RCP is able to perfuse the brain parenchyma in humans during DHCA.

Efficacy of superficial temporal artery pressure-guided selective cerebral perfusion during deep hypothermic circulatory arrest in patients undergoing aortic arch surgery

Objective To evaluate the efficacy of superficial temporal artery(STA)pressure-guided selective cerebral perfusion(SCP)during deep hypothermic circulatory arrest(DHCA)in patients undergoing aortic arch surgery. Methods Ninety-six patients of both sexes, aged 35-64 yr, with body mass index of 19-23 kg/m2, of American Society of Anesthesiologists physical status Ⅲ or Ⅳ, undergoing aortic arch surgery, were divided into STA pressure group(group A)and clinical experience group(group B)using a random number table, with 48 patients in each group.In group A, STA catheterization was performed after tracheal intubation, and arterial pressure was monitored.SCP flow was adjusted to maintain the target value of STA pressure between 30 and 40 mmHg during DHCA in group A. SCP flow rate was set at 5-10 ml·kg-1·min-1 according to clinical experience in group B. The volume of fluid perfused during SCP, emergence time, extubation time and duration of intensive care unit stay were recorded.Neurological function was evaluated during length of hospitalization after surgery, and the development of permanent and transient neurological dysfunction and mortality in hospital were recorded. Results Compared with group B, the volume of fluid perfused during SCP was significantly decreased, the emergence time, extubation time and duration of intensive care unit stay were shortened, the incidence of permanent and transient neurological dysfunction(2% and 4%, respectively)was decreased(P 0.05). Conclusion Maintaining STA pressure at 30-40 mmHg is a reliable method for guiding SCP during DHCA in patients undergoing aortic arch surgery. Key words: Temporal arteries; Blood pressure; Cerebrovascular circulation; Circulatory arrest, deep hypothermia induced; Prognosis

Retrograde Cerebral Perfusion Results in Better Perfusion to the Striatum Than the Cerebral Cortex During Deep Hypothermic Circulatory Arrest: A Microdialysis Study.

It remains controversial whether contemporary cerebral perfusion techniques, utilized during deep hypothermic circulatory arrest (DHCA), establish adequate perfusion to deep structures in the brain. This study aimed to investigate whether selective antegrade cerebral perfusion (SACP) or retrograde cerebral perfusion (RCP) can provide perfusion equally to various anatomical positions in the brain using metabolic evidence obtained from microdialysis. Eighteen piglets were randomly assigned to 40 min of circulatory arrest (CA) at 18°C without cerebral perfusion (DHCA group, n = 6) or with SACP (SACP group, n = 6) or RCP (RCP group, n = 6). Microdialysis parameters (glucose, lactate, pyruvate, and glutamate) were measured every 30 min in cortex and striatum. After 3 h of reperfusion, brain tissue was harvested for Western blot measurement of α-spectrin. After 40 min of CA, the DHCA group showed marked elevations of lactate and glycerol and a reduction in glucose in the microdialysis perfusate (all P < 0.05). The changes in glucose, lactate, and glycerol in the perfusate and α-spectrin expression in brain tissue were similar between cortex and striatum in the SACP group (all P > 0.05). In the RCP group, the cortex exhibited lower glucose, higher lactate, and higher glycerol in the perfusate and higher α-spectrin expression in brain tissue compared with the striatum (all P < 0.05). Glutamate showed no difference between cortex and striatum in all groups (all P > 0.05). In summary, SACP provided uniform and continuous cerebral perfusion to most anatomical sites in the brain, whereas RCP resulted in less sufficient perfusion to the cortex but better perfusion to the striatum.

Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: Does the use of thiopental provide added cerebral protection during deep hypothermic circulatory arrest (DHCA)? Altogether, more than 62 papers were found using the reported search, of which 7 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Four of the seven papers used thiopental alongside other neuroprotective methods and agents. The methods included the use of ice packs to the head and core systemic hypothermia. Agents used alongside thiopental included nicardipine and mannitol. Thiopental was found to have the ability to lower oxygen consumption, where oxygen consumption was measured using the phosphocreatinine and adenosine triphosphate ratio. The neuroprotective effect of thiopental was evaluated by assessing the electrical activity of the brain during circulatory arrest, by which it was shown to be advantageous. However, other trials suggested that adding thiopental during circulatory arrest did not provide any extra protection to the brain. The timing of thiopental administration is of importance in order to gain positive outcomes, as it's ability to lower the cerebral energy state may result in unfavourable results if added before hypothermic circulatory arrest, where this may lead to an ischaemic event. We conclude that the use of thiopental during deep hypothermic circulatory arrest is beneficial, but if administered too early, it may replete the cerebral energy state before arrest and prove to be detrimental.

Predictors of electrocerebral inactivity with deep hypothermia

Cooling to electrocerebral inactivity (ECI) by electroencephalography (EEG) remains the gold standard to maximize cerebral and systemic organ protection during deep hypothermic circulatory arrest (DHCA). We sought to determine predictors of ECI to help guide cooling protocols when EEG monitoring is unavailable. Between July 2005 and July 2011, 396 patients underwent thoracic aortic operation with DHCA; EEG monitoring was used in 325 (82%) of these patients to guide the cooling strategy, and constituted the study cohort. Electroencephalographic monitoring was used for all elective cases and, when available, for nonelective cases. Multivariable linear regression was used to assess predictors of the nasopharyngeal temperature and cooling time required to achieve ECI. Cooling to a nasopharyngeal temperature of 12.7°C or for a duration of 97 minutes was required to achieve ECI in >95% of patients. Only 7% and 11% of patients achieved ECI by 18°C or 50 minutes of cooling, respectively. No independent predictors of nasopharyngeal temperature at ECI were identified. Independent predictors of cooling time included body surface area (18 minutes/m(2)), white race (7 minutes), and starting nasopharyngeal temperature (3 minutes/°C). Low complication rates were observed (ischemic stroke, 1.5%; permanent paraparesis/paraplegia, 1.5%; new-onset dialysis, 2.2%; and 30-day/in-hospital mortality, 4.3%). Cooling to a nasopharyngeal temperature of 12.7°C or for a duration of 97 minutes achieved ECI in >95% of patients in our study population. However, patient-specific factors were poorly predictive of the temperature or cooling time required to achieve ECI, necessitating EEG monitoring for precise ECI detection.

Long‐term survival after radical surgery for renal cell carcinoma with tumour thrombus extension into the right atrium

What's known on the subject? and What does the study add? Surgical treatment of renal cell carcinoma (RCC) with tumour thrombus extending into the right atrium remains, despite its complexity and specific technical aspects, the only radical therapeutic option. This single-centre study, unique in size for this rare condition, reports early and late results over a period of 18 years. All patients were operated on using a standardised protocol with use of cardiopulmonary bypass and deep hypothermic circulatory arrest. Overall and cancer-specific cumulative survival was better than in other reports. To evaluate the long-term results of radical surgical management of renal cell carcinoma (RCC) with tumour thrombus extension (TTE) level IV into the right atrium (RCC/TTE IV) in a large single-institution series. Radical complex urological and cardio-surgical procedure was performed over a period of 18 years (1993-2010) on 21 patients with RCC/TTE IV. A radical nephrectomy was performed followed by sternotomy, institution of cardiopulmonary bypass and extraction of the intracardiac tumour thrombus under direct visual control during deep hypothermic circulatory arrest (DHCA). Perioperative and postoperative variables, and long-term overall and cancer-specific survival using the Kaplan-Meier method were analysed. In all patients, precise removal of tumour thrombus was accomplished in a bloodless field during DHCA. The mean (sd) duration of circulatory arrest was 16 (6) min at a mean hypothermia of 20 (3) °C. In-hospital mortality was 9.5% (two patients). The median survival (including in-hospital mortality) was 25 months. In Kaplan-Meier analysis, 2- and 5-year overall cumulative survival rate was 57 (95% confidence interval, CI 36-78)% and 37 (95% CI 15-58)%, respectively. Cancer-specific cumulative survival was 68 (95% CI 49-89)% at 2 years and 51 (95% CI 28-74)% at 5 years. Late outcome after radical surgical treatment in patients with RCC and TTE reaching up to the right atrium justifies this extensive procedure. Cardiopulmonary bypass with DHCA allows safe and precise extirpation of all intracaval and intracardiac tumour mass.

The Optimal Flow Rate for Antegrade Cerebral Perfusion During Deep Hypothermic Circulatory Arrest

The aim of this study is to compare cerebral protection using antegrade cerebral perfusion (ACP) with various flow rates during deep hypothermic circulatory arrest (DHCA) in a piglet model. Twenty-three piglets were randomized to five groups: the control group (n = 3), DHCA group (n = 5), ACP25 group (n = 5), ACP50 group (n = 5), and ACP80 group (n = 5). Three control piglets did not undergo operations. Twenty piglets underwent cardiopulmonary bypass (CPB) and DHCA for 60 min at 20°C. ACP was conducted at 0, 25, 50, and 80 mL/kg/min in the DHCA, ACP25, ACP50, and ACP80 group, respectively. Serum S-100B protein and neuron-specific enolase were monitored, and brain tissues were assayed for the activities of caspase-3 and stained for the evidence of apoptotic cellular injury. Rise in serum S-100B level (post-CPB-pre-CPB) in the ACP50 group was significantly lower than that in the ACP80 group (P = 0.001). Caspase-3 levels were significantly elevated in the ACP80 group compared with the ACP25 (P = 0.041) and ACP50 group (P = 0.01), while positive terminal deoxyneucleotidyl transferase-mediated biotin-dUTP nick end labeling reaction scores in the ACP80 group were significantly higher than those in the ACP25 (P = 0.043) and ACP50 group (P = 0.023). Cerebral protection effects of ACP at 25 and 50 mL/kg/min were superior to that of ACP at 80 mL/kg/min as determined by cerebral markers, immunology, and histology.

Falsely increased bispectral index score during deep hypothermic circulatory arrest in cardiac surgery

The bispectral index score (BIS) is widely used as an accurate measure of the hypnotic effect of anesthetics and sedative drugs [1]. However, some clinical situations can lead to inaccuracy in its results [2]. We report two cases in which the BIS value constantly exceeded the expected levels during deep hypothermic circulatory arrest (DHCA) in cardiac surgery. A 60-year-old male patient was diagnosed with a type III chronic aortic dissection accompanied by a thoracic aortic aneurysm and severe aortic valve regurgitation (AR). He was scheduled to undergo replacement of the descending thoracic aorta. He underwent Bentall surgery 1 year ago; however, this was complicated by third-degree atrioventricular block with an escape rate of less than 40 beats per minute. Therefore, he had a pacemaker implanted set in the DDD mode (Dual chamber pacing, Dual chamber sensing, Dual chamber function mode). The pacemaker mode was transformed to the DOO mode (Dual chamber pacing, No sensing, No function) before the induction because a fixed rate pacing mode such as the DOO mode can reduce the effect of electromagnetic interference. Anesthesia was induced with 14 mg etomidate, 50 mg rocuro nium, and continuous infusion of remifentanil and propofol. Intra-arterial catheters were inserted, and intubation was performed. We reduced the continuous infusion of rocuronium to 2 μg/kg/min for adequate motor evoked potential (MEP) monitoring. A Swan-Ganz central venous catheter was placed in the left subclavian vein. Another central venous catheter was placed in the left internal jugular vein. Cerebrospinal fluid drainage was also performed at L3-4. Before aortic cross clamping, the patient was cooled to a body temperature of 16.3 o

The experience of stent "elephant trunk" procedure in treatment of DeBakey I aortic dissection

Objective To investigate the procedures and outcomes of stent elephant trunk tech-nique in the treatment of DeBakey Ⅰ aortic dissection. Methods Twelve patients (mean 48. 1 years old) with DeBakey Ⅰ aortic dissection were included in our study. During deep hypothermic circulatory arrest (DHCA), selected antegrade cerebral perfusion (SCP) was used to protect the brain. All patients received stent elephant trunk procedure (ascending aorta and arch replacement combined with transluminal stent graft of the descending aorta). Results One patient died after operation (8.3%). The average cardiopul-monary bypass time was (163.2±17.7) min. The average circulatory arrest time was (41.6 ± 12.3) min. Survival patients were followed up for 3 to 6 months and no subsequent death occurred during the fel-low-up period. Conclusion The stent elephant trunk procedure is a simple method with short circulato-ry arrest time. It seems to be effective and safe for DeBakey Ⅰ aortic dissection. Key words: Aortic dissection aneurysm; Stent elephant trunk procedure

Near-Infrared Spectroscopy as a Guide for an Intermittent Cerebral Perfusion Strategy During Neonatal Circulatory Arrest

In view of the existing controversy concerning the best perfusion technique during deep hypothermic circulatory arrest (DHCA) for neonatal heart operations, we examined intraoperative rSO2 to help define an optimal interval for an intermittent antegrade cerebral perfusion (IACP) strategy. Records of patients undergoing stage 1 palliation (S1P) and repair of total anomalous pulmonary venous return (rTAPVR) from 1996 to 2004 were reviewed. A total of 16 patients were identified (11 S1P, 5 rTAPVR) with complete data and long periods of DHCA. A decline in rSO2 of either 20% or below a value of 50 was considered significant. The rSO2 for all patients was evaluated after 5, 10, 15, and 20 minutes of DHCA for significant cerebral desaturation. The average rSO2 at the start of DHCA ranged from 45 to 89 for S1P and 35-86 for rTAPVR. Significant cerebral desaturation was observed in 25%-31% of patients after 5 minutes; 42%-44% of patients after 10 minutes; 58%-69% after 15 minutes; and 75%-83% after 20 minutes. Each neonate has a unique baseline cerebral saturation. Also, the response to DHCA varies among subjects as the rate of decrease of rSO2 was not uniform. Universally applying the same interval after which to perfuse the brain permits significant cerebral desaturation in a large percentage of patients. Cerebral oximetry may provide a guide for developing an individualized cerebral perfusion strategy.

Outcome and quality of life after type-A aortic dissection and correlation with hematocrit during extracorporeal circulation

Objectives: Cerebral perfusion during deep hypothermic circulatory arrest (DHCA) constitutes a major improvement in aortic surgery. Although many different perfusion strategies have been proposed, perfusion via the subclavian artery has gained wide acceptance. Yet, the optimal perfusate in terms of temperature and hematocrit is still matter of ongoing debate. Most recent research questions whether a low hematocrit is really protective.

Arterial Pressure Monitoring During Cardiopulmonary Bypass Using Axillary Arterial Cannulation

W g EMORAL ARTERIAL cannulation had been used as the alternate source of arterial inflow for cardiopulmonary ypass (CPB) when the ascending aorta or arch was unsuitable or various reasons. Right, or rarely left, axillary arterial canulations have become more common, especially when the emoral arteries are not available for arterial cannulation due to evere iliofemoral arterial disease1 or in patients who have evere atherosclerotic disease of the descending thoracic aorta ith floating debris that precludes safe retrograde arterial perusion.2 Right axillary artery cannulation may be the arterial nflow of choice in patients with aortic dissections and aortic neurysms3,4 when selective cerebral perfusion may be necesary during deep hypothermic circulatory arrest (DHCA).5 The uthors report a case in which monitoring of the ipsilateral adial arterial pressure in a patient on CPB using axillary annulation resulted in falsely elevated arterial blood pressures hat led to inappropriate hemodynamic management and hyoxic cerebral injury.

Does antegrade cerebral perfusion protect the brain during deep hypothermic circulatory arrest?

Purpose This study compares cerebral protection using no cerebroplegia and using antegrade cerebroplegia with variable flow rates during deep hypothermic circulatory arrest (DHCA). Methods Twenty healthy neonatal piglets (2.5-3.8 kg) underwent 60 minutes of DHCA. No cerebroplegia was used in group 1 (n = 5). Cold (16°C) antegrade cerebral perfusate was administered through the innominate artery at 10 mL/kg per minute in group 2 (n = 5), at 25 mL/kg per minute in group 3 (n = 5), and at 50 mL/kg per minute in group 4 (n = 5). Venous samples for lactate, pyruvate, S-100B protein, and creatine kinase BB (CKBB) were drawn from the jugular vein before and after discontinuation of cardiopulmonary bypass—lactate at 5 minutes postbypass, pyruvate at 5 minutes postbypass, S-100B protein at 30 minutes postbypass, and CKBB at 6 hours postbypass. Piglets were killed 6 hours postbypass and their brains were harvested for histological/immunologic studies. Extent of damage was assessed using a semiquantitative score of 0 to 4 based on a validated method. Results Evidence for significant apoptosis and necrosis was apparent in all groups. The mean H&E score was 2.2 for group 1, 2.3 for group 2, 2.5 for group 3, and 2.3 for group 4. The mean terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling score was 1.0 for group 1, 1.2 for group 2, 1.7 for group 3, and 0.8 for group 4. Pathological changes were not greater in the piglets that did not have antegrade cerebral perfusion. Serum lactate, pyruvate, S-100B protein, and CKBB did not distinguish between perfusion strategies. Conclusions In neonates, unmodified antegrade cerebral perfusion at flow rates of 10, 25, and 50 mL/kg per minute during DHCA does not provide additional protection of the brain as determined by histology, immunology, serum lactate, pyruvate, S-100B protein, and CKBB.

Hypothermia induced platelet aggregation: No effect of aprotinin (trasylol) but inhibition by eptifibatide (integrilin)

Objectives: The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversially discussed, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has recently been shown to preserve platelet-function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet-function under conditions of DHCA.

Hypothermia-Induced Platelet Aggregation: No Effect of Aprotinin (Trasylol®) but Inhibition by Eptifibatide (Integrilin®)

The serine-protease inhibitor aprotinin protects platelet function during cardiopulmonary bypass. However, its safety and efficacy during deep hypothermic circulatory arrest (DHCA) is controversial, and aprotinin is suspected to cause thrombosis especially during hypothermia. The platelet GP IIb/IIIa inhibitor eptifibatide has been assumed to preserve platelet function during cardiopulmonary bypass without increasing bleeding complications. The aim of this study was to compare the effect of aprotinin and eptifibatide on platelet function under conditions of DHCA. Heparinized blood from healthy volunteers (n = 10) was incubated in stasis for 30 minutes at 18 degrees C to simulate DHCA and compared to samples incubated at 37 degrees C. The effect of eptifibatide (2.5 microg/ml) and aprotinin (300 KIU/ml) on platelets under these conditions was analyzed by flow cytometry. Platelet aggregates were identified using CD41-antibody binding and size. GPIIb/IIIa function was evaluated with the activation-specific antibody PAC-1 after stimulation with 10 microM ADP. Aggregate numbers and antibody mean-fluorescence are reported as mean +/- standard deviation. Hypothermia induced a 2.5-fold increase of aggregates ( p < 0.001) and a 2.6-fold increase of GPIIb/IIIa activation ( p < 0.001). This effect was not influenced by aprotinin but almost completely inhibited by eptifibatide ( p < 0.001). Aprotinin has no procoagulatory effect on platelet function during hypothermia but is not protective either. Eptifibatide inhibits hypothermia-induced platelet aggregation in vitro and may prevent aggregate sequestration in the microvasculature and consecutive ischemic organ damage in vivo.

The Assessment of Brain Injury with Measurement of Calcium Fluorescent Intensity of a Vital Brain Slice

Retrograde cerebral perfusion (RCP) is one of cerebral protection methods during deep hypothermic circulatory arrest (DHCA). However, the mechanism is unclear. In this study with laser confocal scanning microscope (LCSM), calcium fluorescent intensity of vital brain slice was compared between RCP and DHCA group. Sixteen swine, weighing from 19 – 20 kg and supplied by Beijing College of Agriculture, were used for the experiment. After 90 min of DHCA or RCP through the superior vena cava, the animals were rewarmed for 120 min. Through tentorium of the cerebellum and enucleation of the eyeball, vital brain slices (cerebellula and retina) were obtained and fluorescein labeled in artificial cerebrospinal fluid containing 5 μmol/L Fluo-3/AM (fluoresence probe). The calcium fluorescent intensity was examined by LCSM. The results indicated that calcium fluorescent intensity of vital brain slice was lower in the RCP group (cerebellula, 9.16 ± 3.98; retina, 21.48 ± 14.27) than that in the DHCA group (cerebellula, 31.97 ± 20.59; retina, 44.07 ± 21.01) (p &lt; .05). More moderate and severe eosinophilic degeneration was found in the DHCA group than in the RCP group (p &lt; .05) through morphological examination. The statistical analysis also indicated the calcium fluorescent intensity of the vital brain slice was correlated with the level of moderate and severe eosinophilic degeneration of thee neuron (r = 0.86, p &lt; .05). So “calcium overload” contributes to the injury of neuron after DHCA. RCP is able to attenuate “calcium overload,” which has the effect of cerebral protection.