Cerebral oxygen metabolism during total body flow and antegrade cerebral perfusion at deep and moderate hypothermia

The aim of this study is to evaluate the effect of temperature on cerebral oxygen metabolism at total body flow bypass and antegrade cerebral perfusion (ACP). Neonatal piglets were put on cardiopulmonary bypass (CPB) with the initial flow rate of 200 mL/kg/min. After cooling to 18°C (n = 6) or 25°C (n = 7), flow was reduced to 100 mL/kg/min (half‐flow, HF) for 15 min and ACP was initiated at 40 mL/kg/min for 45 min. Following rewarming, animals were weaned from bypass and survived for 4 h. At baseline, HF, ACP, and 4 h post‐CPB, cerebral blood flow (CBF) was measured using fluorescent microspheres. Cerebral oxygen extraction (CEO₂) and cerebral metabolic rate of oxygen (CMRO₂) were monitored. Regional cranial oxygen saturation (rSO₂) was continuously recorded throughout the procedure using near‐infrared spectroscopy. At 18°C, CBF trended lower at HF and ACP and matched baseline after CPB. CEO₂ trended lower at HF and ACP, and trended higher after CPB compared with baseline. CMRO₂ at ACP matched that at HF. Cranial rSO₂ was significantly greater at HF and ACP (P < 0.001, P < 0.001) and matched baseline after CPB. At 25°C, CBF trended lower at HF, rebounded and trended higher at ACP, and matched baseline after CPB. CEO₂ was equal at HF and ACP and trended higher after CPB compared with baseline. CMRO₂ at ACP was greater than that at HF (P = 0.001). Cranial rSO₂ was significantly greater at HF (P = 0.01), equal at ACP, and lower after CPB (P = 0.03). Lactate was significantly higher at all time points (P = 0.036, P < 0.001, and P < 0.001). ACP provided sufficient oxygen to the brain at a total body flow rate of 100 mL/kg/min at deep hypothermia. Although ACP provided minimum oxygenation to the brain which met the oxygen requirement, oxygen metabolism was altered during ACP at moderate hypothermia. ACP strategy at moderate hypothermia needs further investigation.     

The Effect of Cardiopulmonary Bypass and Hypothermic Circulatory Arrest on Hepatic Histology in Newborn Animals: An Experimental Study

Still little is known about the effect of cardiac surgery on neonatal hepatic tissue. We examined the effect of cardiopulmonary bypass (CPB) and the effect of deep hypothermic circulatory arrest (DHCA) on neonatal hepatic tissue. Liver biopsies of neonatal piglets were taken after CPB (n = 4), after DHCA (n = 5), and after surgery without CPB (non‐CPB; n = 3). Additionally, findings were compared to those of control piglets (n = 9). The liver specimens were fixed, stained with hematoxylin and eosin, and scored regarding inflammatory reaction, hepatocellular edema, and apoptosis. Inflammation score of treated groups was higher than in control; CPB 2.5 ± 0.5, DHCA 1.6 ± 0.4, non‐CPB 1.2 ± 0.6, control 0.4 ± 0.3 (P < 0.001 CPB and DHCA vs. control; P < 0.05 non‐CPB vs. control). Hepatic cell edema was more evident after DHCA (score 2.0 ± 0.4 vs. 0.2 ± 0.3 in control and 0.6 ± 0.5 after CPB; P < 0.001 and P < 0.05, respectively). The highest apoptotic cell count was in the non‐CPB group (22.3 ± 6.3 vs. 11.4 ± 3.6 in control and 8.9 ± 5.4 after CPB; P < 0.05). The present study showed that (i) surgical trauma induces hepatic cell apoptosis; (ii) CPB increases hepatic inflammatory reaction; and (iii) DHCA amplifies hepatic cell edema.     

Carotid Artery Doppler Flow Pattern After Deep Hypothermic Circulatory Arrest in Neonatal Piglets

The mechanisms of cerebral injury after cardiac surgery in neonates are not clear. The aim of the study was the analysis of flow changes in the carotid artery of neonatal piglets after deep hypothermic circulatory arrest (DHCA). Eight neonatal piglets were connected to cardiopulmonary bypass (CPB) and underwent (i) cooling to 18°C core temperature within 30 min, (ii) DHCA for 90 min, and finally (iii) rewarming to 37°C after cross‐clamp release (60 min of reperfusion). The blood flow was measured in the left carotid artery by an ultrasonic flow probe before CPB (baseline; T₀), immediately after termination of reperfusion on CPB (T₁), 30 min later (T₂), and 60 min later (T₃). Additionally, the pulsatility index and the resistance index were calculated and compared. Finally, the relationship between the carotid artery flow and the corresponding pressure at each time‐point was compared. After termination of CPB (T₁), the mean carotid artery flow was reduced from 45.26 ± 2.58 mL/min at baseline to 23.29 ± 2.58 mL/min (P < 0.001) and remained reduced 30 and 60 min later (P < 0.001 vs. baseline). Both the pulsatility index and the resistance index were increased after termination of reperfusion, with the maximum occurring 30 min after CPB end. In conclusion, the carotid artery Doppler flow in neonatal piglets was reduced after DHCA, while the indices of pulsatility and resistance increased.     

幼猪深低温体外循环最适区域性脑灌注流量的实验研究

目的探索幼猪在深低温体外循环中的最适区域性脑灌注（RCP）流量,为先天性心脏病（先心病）小儿患者术中脑保护策略提供理论基础。方法20只健康幼猪,年龄23．7±2．1d,体重6．4±0．6kg,采用随机数字表法分为4组,每组各5例。对照组为单纯深低温停循环（DHCA组）;实验组按不同RCP流量分为3组：RCP25组,流量为25．9±3．0ml（kg·min）;RCP50组,流量为49．7士1．8ml／（kg·rain）;RCP80组,流量为79．5±0．9ml／（kg·min）;通过检测血浆中建立CPB前（T1）、DHCA或RCP前（T2）、RCP结束后10min（T3）、停机前（T4）、CPB结束后1h（Ts）以及2h（T5）6个时间点检测血浆中的S-100β蛋白、神经元特异性烯醇化酶（NSE）的浓度、脑氧摄取率（CEOz）及大脑皮质半胱天冬氨酸酶3（caspase3）的含量,评估不同RCP流量的脑保护效果。结果各组幼猪血浆中S-100β蛋白和NSE的浓度于T4时明显升高,并于T5时达到高峰（P〈0．05）;RCP50组血浆中S-100β蛋白和NSE的浓度从T4时开始明显低于DHCA组和RCP80组（P〈O．05）,与RCP2。组相比,其差异无统计学意义（P〉0．05）。各组CEO2在T1时差异无统计学意义（P〉0．05）,在T2时明显降低（P％0．05）。DHCA组、RCPzs组和RCP50组的CEO2在T3时开始升高,RCP20组在T3时稍微下降,但其差异无统计学意义（P〉0．05）;从T4开始,RCP25组和RCPj。组的CEO。与DHcA组和RCP80组更接近于基础值（T1）（P〈0．05）。大脑皮质中caspase3的含量在3种不同流量的RCP组明显低于DHCA组（F=23．54,P〈0．01）,其中RCP25组及RCP5。组明显低于RCP80组（F=23．54,P〈0．01）,而RCP2s组与RCP50组的caspase3含量差异无统计学意义（P〉0．05）。结论在我们建立的幼猪深低温体外循环模型中,RCP最适灌注流量为25～50ml／（kg·rain）,并且趋向于50ml／（kg·rain）。     

Similar Cerebral Protective Effectiveness of Antegrade and Retrograde Cerebral Perfusion During Deep Hypothermic Circulatory Arrest in Aortic Surgery: A Meta‐Analysis of 7023 Patients

In aortic arch surgery, deep hypothermic circulatory arrest (DHCA) combined with cerebral perfusion is employed worldwide as a routine practice. Even though antegrade cerebral perfusion (ACP) is more widely used than retrograde cerebral perfusion (RCP), the difference in benefit and risk between ACP and RCP during DHCA is uncertain. The purpose of this meta‐analysis is to compare neurologic outcomes and early mortality between ACP and RCP in patients who underwent aortic surgery during DHCA. PubMed, EMBASE, and the Cochrane Library were searched using the key words “antegrade,” “retrograde,” “cerebral perfusion,” “cardiopulmonary bypass,” “extracorporeal circulation,” and “cardiac surgery” for studies reporting on clinical endpoints including early mortality, stroke, temporary neurologic dysfunction (TND), and permanent neurologic dysfunction (PND) in aortic surgery requiring DHCA with ACP or RCP. Heterogeneity was analyzed with the Cochrane Q statistic and I² statistic. Publication bias was tested with Begg's funnel plot and Egger's test. Thirty‐four studies were included in this meta‐analysis, with 4262 patients undergoing DHCA + ACP and 2761 undergoing DHCA + RCP. The overall pooled relative risk for TND was 0.722 (95% CI = [0.579, 0.900]), and the z‐score for overall effect was 2.9 (P = 0.004). There was low heterogeneity (I² = 18.7%). The analysis showed that patients undergoing DHCA + ACP had better outcomes than those undergoing DHCA + RCP in terms of TND, while there were no significant differences between groups in terms of PND, stroke, and early mortality. This meta‐analysis indicates that DHCA + ACP has an advantage over DHCA + RCP in terms of TND, while the two methods show similar results in terms of PND, early mortality, and stroke.     

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.     

Pyruvate Effects on Red Blood Cells During In Vitro Cardiopulmonary Bypass With Dogs’ Blood

To investigate the effects of pyruvate (Pyr) on adenosine triphosphate (ATP), endothelial nitric oxide synthase (eNOS), and nitric oxide (NO) in red blood cells (RBCs) during the cardiopulmonary bypass procedure (CPB), blood, 500 mL, was collected from each of 10 healthy dogs (weight 12–18 kg). The blood was divided into two parts (250 mL each) and randomly assigned into the control group (Group C, n = 10) or the Pyr group (Group P, n = 10). The blood was commingled with an equal volume of 0.9% NaCl and pyruvated isotonic solution (Pyr 50 mM) in the extracorporeal circuit in the two groups, respectively. The CPB procedure was fixed at 120 min, and the transferring flow was 4 L/min. Contents of ATP in RBCs, eNOS activities, and NO productions in plasma were measured before CPB and during CPB at 30, 60, 90, and 120 min in both groups. The ATP level, eNOS activity, and NO production were not different prior to CPB between the two groups. A decline of ATP levels was shown in both groups but remained significantly higher in Group P than in Group C at the same time points during in vitro CPB (P < 0.01). Values of eNOS and NO were significantly increased in Group C but markedly reduced in Group P during CPB, compared with pre‐CPB (P < 0.01). The CPB procedure significantly damaged dogs’ RBCs in the ATP level, eNOS activity, and NO production, in vitro, but Pyr effectively protected RBCs in these functions during CPB. Pyr would be clinically protective for RBCs during CPB.     

Cerebral metabolism during deep hypothermic circulatory arrest vs moderate hypothermic selective cerebral perfusion in a piglet model: a microdialysis study

Background: Few data exist regarding antegrade selective cerebral perfusion (ASCP) and its application in newborn and juvenile patients. Clinical data suggest ASCP alone to be superior to deep hypothermic circulatory arrest (DHCA); however, the effects of moderate hypothermia during ASCP on cerebral metabolism in this patient population are still unclear. Methods: After obtaining the approval from animal investigation committee, 16 piglets were randomly assigned to circulatory arrest combined with either ASCP at 27°C or DHCA at 18°C for 90 min. Cerebral oxygen extraction fraction (COEF) from blood as well as cerebral tissue glucose, glycerol, lactate, pyruvate, and the lactate/pyruvate ratio (L/P ratio) by microdialysis were obtained repeatedly. Results: COEF was lower during cooling and rewarming, respectively, in the DHCA18 group compared to the ASCP27 group (30 ± 8 vs 56 ± 13% and 35 ± 6 vs 58 ± 7%, respectively). Glucose decreased in both the DHCA18 and ASCP27 groups during the course of cardiopulmonary bypass (CPB), but were higher in the ASCP27 group during ASCP, compared to the DHCA18 group during circulatory arrest (0.7 ± 0.1 vs 0.2 ± 0.1 mm ·l^?1, P < 0.05). Pyruvate was higher (ASCP27 vs DHCA18: 53 ± 17 vs 6 ± 2 μm ·l^?1, P < 0.05), and the L/P ratio increased during circulatory arrest in the DHCA18 group, compared to the selective perfusion phase of the ASCP27 group (DHCA18 vs ASCP27: 1891 ± 1020 vs 70 ± 28, P < 0.01). Conclusions: In this piglet model, both cerebral oxygenation and microdialysis findings suggested a depletion of cerebral energy stores during circulatory arrest in the DHCA18 group, compared to selective cerebral perfusion combined with circulatory arrest in the ASCP27 group.     

Histidine‐Tryptophan‐Ketoglutarate Solution With Added Ebselen Augments Myocardial Protection in Neonatal Porcine Hearts Undergoing Ischemia/Reperfusion

Whether modified histidine‐tryptophan‐ketoglutarate (HTK) solution offers myocardial protection to newborn heart has not been documented. The purpose of this study was to compare myocardial protection using HTK added by ebselen with HTK in a piglet model of cardiopulmonary bypass (CPB). Fifteen piglets were randomly assigned to three groups: the control group (C group, n = 5), HTK solution group (HTK group, n = 5), and HTK added by 10 nM ebselen group (HTK+E group, n = 5). Animals in the two experimental groups were placed on hypothermic CPB, after which the ascending aorta had been clamped for 2 h. The control animals underwent normothermic CPB without cardiac arrest. Myocardial antioxidant activities, myocytes apoptosis and mitochondrial structures, as well as the release of cytochrome c and the expression of Bax, Bcl‐2, and HSP72 protein in myocardium were measured. Increased myocardial superoxide dismutase (SOD) and Mn‐SOD activities, decreased TUNEL‐positive cells, and reduced release of cytochrome c were noted in the HTK+E group compared with those in the HTK group (P = 0.021, P = 0.020, P = 0.045, and P = 0.010, respectively). The Bax/Bcl‐2 ratio in the HTK group was significantly higher than that in the C group (P = 0.024). The expression of HSP72 protein and mRNA in the HTK+E group was higher than that in the HTK group (P = 0.039 and P = 0.035, respectively). Mitochondrial score under electron microscope in the HTK+E group was lower than that in the HTK group (P = 0.047). Improved antioxidant defense, reduced myocytes apoptosis, and better preserved mitochondrial structure were observed in the HTK+E group. Ebselen added to HTK provides better myocardioprotection to HTK solution for the neonatal heart.     

Effect of a Miniaturized Cardiopulmonary Bypass System on the Inflammatory Response and Cardiac Function in Neonatal Piglets

The cognitive impairment and hemodynamic instability after neonatal cardiac surgery with cardiopulmonary bypass (CPB) might be exacerbated by hemodilution. Therefore, this study investigated the impact of different bloodless prime volumes on the hemodynamics and the inflammatory response by a miniaturized CPB system in neonatal piglets. The bypass circuit consisted of a Capiox RX05 (Capiox Baby RX, Terumo Corp., Tokyo, Japan) oxygenator and 3/16 internal diameter arterial and venous polyvinyl chloride tubing lines, with a minimum 75 mL prime volume. Twelve 1‐week‐old piglets were placed on a mild hypothermic CPB (32°C) at 120 mL/kg/min for 2 h. The animals were divided into two groups, based on the volume of the prime solution. The priming volume was 75 mL in Group I and 175 mL in Group II. No blood transfusions were performed, and no inotropic or vasoactive drugs were used. The interleukin‐6 (IL‐6) and thrombin‐antithrombin (TAT) complex levels, as well as right ventricular and pulmonary functions, were measured before and after CPB. Group I had low levels of IL‐6 and TAT immediately after CPB (4370 ± 2346 vs. 9058 ± 2307 pg/mL, P < 0.01 and 9.9 ± 7.7 vs. 25.1 ± 8.8 ng/mL, P < 0.01, respectively). Group I had significantly improved cardiopulmonary function, cardiac index (0.22 ± 0.03 vs. 0.11 ± 0.05 L/kg/min, P < 0.001), and pulmonary vascular resistance index (7366 ± 2860 vs. 28 620 ± 15 552 dynes/cm⁵/kg, P < 0.01) compared with Group II. The miniaturized bloodless prime circuit for neonatal CPB demonstrated that the influence of hemodilution can reduce the subsequent inflammatory response. In addition, a low prime volume could therefore be particularly effective for attenuating pulmonary vascular resistance and right ventricular dysfunction in neonates.     

Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open‐heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m². The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20‐min test during which CPB was adjusted to the minimum flow to maintain MVO₂ >70% and rSO₂ >45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2 >70% and rSO2 >45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20‐min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.     

Preoperative high dose methylprednisolone attenuates the cerebral response to deep hypothermic circulatory arrest.

OBJECTIVE: The aim of this study was to assess the effects of preoperative high dose methylprednisolone on cerebral recovery following a period of deep hypothermic circulatory arrest (DHCA). METHODS: Sixteen 1-week-old piglets were randomized to placebo (n=8), or 30 mg/kg intramuscular methylprednisolone sodium succinate (MPRED) given at 8 and 2 h before induction of anaesthesia. All piglets underwent cardiopulmonary bypass, cooling to 18 degrees C, 60 min of circulatory arrest followed by 60 min of reperfusion and rewarming. The radiolabelled microsphere method was used to determine the global and regional cerebral blood flow (CBF) and cerebral oxygen metabolism (CMRO(2)) at baseline before DHCA and after 60 min of reperfusion. RESULTS: In controls, mean global CBF (+/-1 standard error) before DHCA was 53.7+/-2.4 ml/100 g per min and fell to 23.8+/-1.2 ml/100 g per min following DHCA (P<0.0001). This represents a post-DHCA recovery to 45.1+/-3.3% of the pre-DHCA value. In the MPRED group recovery of global CBF post-DHCA was significantly higher at 63.6+/-5.2% of the pre-DHCA value (P=0.009). The regional recovery of CBF in the cerebellum, brainstem and basal ganglia was 80, 75 and 69% of pre-DHCA values in the MPRED group respectively compared to 66, 60 and 55% in controls (P<0.05). Global CMRO(2) in controls fell from 3.9+/-0.2 ml/100 g per min before to 2. 3+/-0.2 ml/100 g per min after DHCA (P=0.0001). This represents a post-DHCA recovery to 58.6+/-4.4% of the pre-DHCA value. In the MPRED group, however, recovery of global CMRO(2) post-DHCA was significantly higher at 77.9+/-7.1% of the pre-DHCA value (P=0.04). CONCLUSIONS: Treatment with high dose methylprednisolone at 8 and 2 h preoperatively attenuates the normal cerebral response to a period of deep hypothermic ischaemia. This technique may therefore offer a safe and inexpensive strategy for cerebral protection during repair of congenital heart defects with the use of DHCA.     

Multisite Near Infrared Spectroscopy During Cardiopulmonary Bypass in Pediatric Patients

Multisite near infrared spectroscopy (NIRS) monitoring during pediatric cardiopulmonary bypass (CPB) has not been extensively validated. Although it might be rational to explore regional tissue saturation at different body sites (namely brain, kidney, upper body, lower body), conflicting results are currently provided by experience in children. The aim of our study was to evaluate absolute values of multisite NIRS saturation during CPB in a cohort of infants undergoing pediatric cardiac surgery to describe average differences between cerebral, renal, upper body (arm), and lower body (thigh) regional saturation. Furthermore, the correlation between cerebral NIRS and cardiac index (CI) at CPB weaning was evaluated. Twenty‐five infants were enrolled: their median weight, age, and body surface area were 3.9 (3.3–6) kg, 111 (47–203) days, and 0.24 (0.22–0.33) m², respectively. Median Aristotle score was 8 (6–10), and vasoactive inotropic score at CPB weaning was 16 (14–25). A total of 17 430 data points were recorded by each sensor: two‐way ANOVA showed that time (P < 0.0001) and site (P = 0.0001) significantly affected variations of NIRS values: however, if cerebral NIRS values are excluded, sensor site is no more significant (P = 0.184 in the no circulatory arrest [noCA] group and P = 0.42 in the circulatory arrest [CA] group). Analysis of NIRS saturation changes over time showed that, at all sites, average NIRS values increased after CPB start, even if the increase of cerebral saturation was less intense than other sites (P < 0.0001). Detailed analysis of interaction between site of NIRS measurement and time point showed that cerebral NIRS (ranging from 65 to 75%) was always significantly lower than that of other channels (P < 0.0001) that tended to be in the range of oversaturation (80–90%), especially during the CPB phase. Average cerebral NIRS values of patients who did not undergo circulatory arrest (CA) during CPB, 10 min after CPB weaning, were associated with average CI values with a significant correlation (r = 0.7, P = 0.003). In conclusion, during CPB, cerebral NIRS values are expected to remain constantly lower than somatic sensors, which instead tend to show similar elevated saturations, regardless of their position. Based on these results, positioning of noncerebral NIRS sensors during CPB without CA may be questioned.     

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.     

Pulsatile flow improves cerebral blood flow in pediatric cardiopulmonary bypass

The objective of this study was to evaluate the effect of pulsatile flow on cerebral blood flow (CBF) in infants with the use of a mild hypothermic cardiopulmonary bypass (CPB). Thirty infants scheduled for open heart surgery were randomized to the pulsatile group (Group P, n = 15) and nonpulsatile group (Group NP, n = 15). In Group P, pulsatile perfusion was applied during the aortic cross‐clamping period, whereas nonpulsatile perfusion was used in Group NP. The systolic peak velocity (Vs), the end of diastolic velocity (Vd), the mean velocity (Vm), and the pulsatility index (PI) and the resistance index (RI) of the middle cerebral artery were measured by a transcranial Doppler (TCD) ultrasound after anesthesia (T1; baseline), at the beginning of CPB (T2), 10 min after aortic cross‐clamping (T3), 3 min after declamping (T4), at the cessation of CPB (T5), and at the end of the operation (T6). During T3 and T4, the Vs in Group P was significantly higher than in Group NP. However, there were no statistically significant differences between Vd and Vm. The PI and RI in Group P were also higher than those in Group NP (both P < 0.05). During T5, Vd and Vm were higher in Group P (P < 0.05), whereas there was no difference in Vs. Additionally, PI and RI in Group P were significantly lower than those in Group NP (P < 0.05). However, there was no difference during T6. Pulsatile perfusion may increase CBF and decrease cerebral vascular resistance in the early period after mild hypothermic CPB.     

Large-dose pretreatment with methylprednisolone fails to attenuate neuronal injury after deep hypothermic circulatory arrest in a neonatal piglet model

Conflicting results have been reported with regard to the neuroprotective effects of steroid treatment with cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). We evaluated the mode and severity of neuronal cell injury in neonatal piglets after prolonged DHCA and the possible neuroprotective effect of systemic pretreatment (>6 h before surgery) with large-dose methylprednisolone (MP). Nineteen neonatal piglets (age, <10 days; weight, 2.1 +/- 0.5 kg) were randomly assigned to 2 groups: 7 animals were pretreated with large-dose systemic MP (30 mg/kg) 24 h before surgery, and 12 animals without pharmacological pretreatment (saline) served as control groups. All animals were connected to full-flow CPB with cooling to 15 degrees C and 120 min of DHCA. After rewarming to 38.5 degrees C with CPB, animals were weaned from CPB and survived 6 h before they were killed, and the brain was prepared for light and electron microscopy, immunohistochemistry, and TUNEL-staining. Quantitative histological studies were performed in hippocampus, cortex, cerebellum, and caudate nucleus. Systemic pretreatment with large-dose MP lead to persistent hyperglycemia but no significant changes of cerebral perfusion. Necrotic and apoptotic neuronal cell death were detected in all analyzed brain regions after 120 min of DHCA. In comparison to the control group, large-dose pretreatment with systemic MP lead to an increase of necrotic neuronal cell death and induced significant neuronal apoptosis in the dentate gyrus of the hippocampus (P = 0.001). In conclusion, systemic pretreatment with large-dose MP fails to attenuate neuronal cell injury after prolonged DHCA and induces regional neuronal apoptosis in the dentate gyrus.     

Pediatric physiologic pulsatile pump enhances cerebral and renal blood flow during and after cardiopulmonary bypass

Controversy over benefits of pulsatile flow after pediatric cardiopulmonary bypass (CPB) continues. Our study objectives were to first, quantify pressure and flow waveforms in terms of hemodynamic energy, using the energy equivalent (EEP) formula, for direct comparisons, and second, investigate effects of pulsatile versus nonpulsatile flow on cerebral and renal blood flow, and cerebral vascular resistance during and after CPB with deep hypothermic circulatory arrest (DHCA) in a neonatal piglet model. Fourteen piglets underwent perfusion with either an hydraulically driven dual-chamber physiologic pulsatile pump (P, n = 7) or a conventional nonpulsatile roller pump (NP, n = 7). The radiolabeled microsphere technique was used to determine the cerebral and renal blood flow. P produced higher hemodynamic energy (from mean arterial pressure to EEP) compared to NP during normothermic CPB (13 +/- 3% versus 1 +/- 1%, p < 0.0001), hypothermic CPB (15 +/- 4% versus 1 +/- 1%, p < 0.0001) and after rewarming (16 +/- 5% versus 1 +/- 1%, p < 0.0001). Global cerebral blood flow was higher for P compared to NP during CPB (104 +/- 12 ml/100g/min versus 70 +/- 8 ml/100g/min, p < 0.05). In the right and left hemispheres, cerebellum, basal ganglia, and brainstem, blood flow resembled the global cerebral blood flow. Cerebral vascular resistance was lower (p < 0.007) and renal blood flow was improved fourfold (p < 0.05) for P versus NP, after CPB. Pulsatile flow generates higher hemodynamic energy, enhancing cerebral and renal blood flow during and after CPB with DHCA in this model.     

深低温停循环下兔脑内兴奋性氨基酸的早期变化与脑损伤研究

目的　探讨体外循环(CPB)和深低温停循环(DHCA)下脑内兴奋性氨基酸(EAA )早期变化规律,及其“兴奋毒性”作用在脑损伤中的作用。方法　建立应用脑微透析技术的兔CPB和DHCA模型。利用高效液相的电化学检测方法,测定兔脑海马CA1区脑细胞间液中EAA的连续性变化。术后利用透射电子显微镜给予组织学损伤评分。结果　谷氨酸在CPB组各阶段变化差异无统计学意义(P >0 .0 5 ) ;DHCA组在恢复循环早期明显升高(P <0 .0 5 ) ,升高程度DHCA组明显高于CPB组(P <0 .0 1)。天冬氨酸在DHCA组恢复灌注3 0～60min阶段明显升高(P <0 .0 1) ,但与CPB组的组间对照差异无统计学意义(P >0 .0 5 )。透射电镜发现两组脑细胞超微结构均明显损伤,DHCA组损伤重于C组(P <0 .0 5 )。结论　“兴奋毒性”作用与中低温CPB造成的脑损伤无关。DHCA可使再灌注早期兴奋性氨基酸升高,并导致脑损伤加重     

Low‐Output Is Not the Cause of Death of Neonatal Piglets Early After Cardiopulmonary Bypass

The mortality rate of neonatal piglets after heart surgery is high. Searching for a possible explanation for the death of neonatal piglets early after cardiopulmonary bypass, we analyzed hemodynamic parameters regarding survival and non‐survival. Initially, 10 neonatal piglets (younger than 7 days) were connected to cardiopulmonary bypass (CPB). The mean body weight was 2.98 ± 0.44 kg. Exposure of the heart was performed through a median sternotomy. After connection to the CPB, the piglets were cooled to 32°C core temperature before the ascending aorta was cross‐clamped and the heart arrested (90 min). Thereafter, piglets were re‐warmed to 37°C and separated from CPB. During follow‐up, the piglets did not receive inotropic support or vasopressors. Piglets who survived at least 2 h after termination of CPB were included in the study for further data analysis (n = 9). Five piglets died 2.5 to 4.0 h (median: 3.5 h) after CPB; these piglets formed the non‐survivors group. Four animals survived the complete follow‐up of 6 h after CPB and formed the survivors group. Regarding contractility (dP/dt_max, dP/dt_max/P, and wall thickening) there were not statistically significant differences between the groups. Non‐survivors showed prolonged decrease of mean arterial pressure of more than 20% of baseline values, corresponding with a value of below 30 mm Hg. In conclusion, the death of neonatal piglets early after cardiopulmonary bypass was not determined by low output.     

Clinical Evaluation of New Generation Oxygenators With Integrated Arterial Line Filters for Cardiopulmonary Bypass

New generation oxygenators with integrated arterial line filters have been marketed to improve the efficacy of cardiopulmonary bypass (CPB). Differences in designs, materials, coating surfaces, pore size of arterial filter, and static prime exist between the oxygenators. Despite abundant preclinical data, literature lacks clinical studies. From September 2010 to March 2011, 80 consecutive patients were randomized to CPB using Terumo Capiox FX25 (40 patients, Group‐T) or Sorin Synthesis (40 patients, Group‐S) oxygenators. Pressure drop and gas exchange efficacy were registered during CPB. High‐sensitivity C‐reactive protein (hs‐CRP), white blood cells (WBCs), fluid balance, activated clotting time, international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, platelets (PLTs), serum albumin, and total proteins were measured perioperatively at different timepoints. Clinical outcome was recorded. Repeated measure analysis of variance and nonparametric statistics assessed between‐groups and during time differences. The two groups showed similar baseline and intraoperative variables. No differences were recorded in pressure drop and gas exchange (group‐P and group*time‐P = N.S. for all) during CPB. Despite similar fluid balance (P = N.S. for static/dynamic priming and ΔVolume administered intraoperatively), Group‐T showed higher hs‐CRP (group‐P = 0.034), aPTT (group‐P = 0.0001), and INR (group‐P = 0.05), with lower serum albumin (group‐P = 0.014), total proteins (group‐P = 0.0001), fibrinogen (group‐P = 0.041), and PLTs (group‐P = 0.021). Group‐T also showed higher postoperative bleeding (group‐P = 0.009) and need for transfusions (P = 0.008 for packed red cells and P = 0.0001 for fresh frozen plasma and total transfused volumes). However, clinical outcome was comparable (P = N.S. for all clinical endpoints). Both oxygenators proved effective and resulted in comparable clinical outcomes. However, Sorin Synthesis seems to reduce inflammation and better preserve the coagulative cascade and serum proteins, resulting in lower transfusions and post‐CPB inflammatory response.