Low-flow Cardiopulmonary Bypass Research Articles

Exogenous nitric oxide delivery protects against cardiopulmonary bypass–associated acute kidney injury: Histologic and serologic evidence from an ovine model

ObjectiveSeveral human studies have associated nitric oxide administration via the cardiopulmonary bypass circuit with decreased incidence of cardiopulmonary bypass–associated acute kidney injury, but histopathologic and serologic evidence of nitric oxide efficacy for acute kidney injury attenuation are lacking. MethodsBy using a survival ovine model (72 hours), acute kidney injury was induced by implementing low-flow cardiopulmonary bypass for 2 hours, followed by full-flow cardiopulmonary bypass for 2 hours. The nitric oxide cohort (n = 6) received exogenous nitric oxide through the cardiopulmonary bypass circuit via the oxygenator, and the control group (n = 5) received no nitric oxide. Serial serologic biomarkers and renal histopathology were obtained. ResultsBaseline characteristics (age, weight) and intraoperative parameters (cardiopulmonary bypass time, urine output, heart rate, arterial pH, and lactate) were equivalent (P > .10) between groups. Postoperatively, urine output, heart rate, respiratory rate, and peripheral arterial saturation were equivalent (P > .10) between groups. Post–cardiopulmonary bypass creatinine elevations from baseline were significantly greater in the control group versus the nitric oxide group at 16, 24, and 48 hours (all P < .05). Histopathologic evidence of moderate/severe acute kidney injury (epithelial necrosis, tubular slough, cast formation, glomerular edema) occurred in 60% (3/5) of the control group versus 0% (0/6) of the nitric oxide group. Cortical tubular epithelial cilia lengthening (a sensitive sign of cellular injury) was significantly greater in the control group than in the nitric oxide group (P = .012). ConclusionsIn a survival ovine cardiopulmonary bypass model, nitric oxide administered with cardiopulmonary bypass demonstrated serologic and histologic evidence of renal protection from acute kidney injury. These results provide insight into 1 potential mechanism for cardiopulmonary bypass–associated acute kidney injury and supports continued study of nitric oxide via cardiopulmonary bypass circuit for prevention of acute kidney injury.

Transfontanellar Contrast-enhanced US for Intraoperative Imaging of Cerebral Perfusion during Neonatal Arterial Switch Operation.

Background Brain injury and subsequent neurodevelopmental disorders are major determinants for later-life outcomes in neonates with transposition of the great arteries (TGA). Purpose To quantitatively assess cerebral perfusion in neonates with TGA undergoing arterial switch operation (ASO) using transfontanellar contrast-enhanced US (T-CEUS). Materials and Methods In a prospective single-center cross-sectional diagnostic study, neonates with TGA scheduled for ASO were recruited from February 2018 to February 2020. Measurements were performed at five time points before, during, and after surgery (T1-T5), and 11 perfusion parameters were derived per cerebral hemisphere. Neonate clinical characteristics, heart rate, mean arterial pressure, central venous pressure, near-infrared spectroscopy, blood gas analyses, ventilation time, time spent in the pediatric intensive care unit, and time in hospital were correlated with imaging parameters. Analysis of variance or a mixed-effects model were used for groupwise comparisons. Results A total of 12 neonates (mean gestational age, 39 6/7 weeks ± 1/7 [SD]) were included and underwent ASO a mean of 6.9 days ± 3.4 after birth. When compared with baseline values, T-CEUS revealed a longer mean time-to-peak (right hemisphere, 4.3 seconds ± 2.1 vs 17 seconds ± 6.4 [P < .001]; left hemisphere, 4.0 seconds ± 2.3 vs 21 seconds ± 8.7 [P < .001]) and rise time (right hemisphere, 3.5 seconds ± 1.7 vs 11 seconds ± 5.1 [P = .002]; left hemisphere, 3.4 seconds ± 2.0 vs 22 seconds ± 7.8 [P = .004]) in both cerebral hemispheres during low-flow cardiopulmonary bypass and hypothermia (T4) for all neonates. Neonate age at surgery negatively correlated with T-CEUS parameters during ASO, as calculated with the area under the flow curve (AUC) during wash-in (R = -0.60, P = .020), washout (R = -0.82, P = .002), and both wash-in and washout (R = -0.79, P = .004). Mean AUC values were lower in neonates older than 7 days compared with younger neonates during wash-in ([87 arbitrary units {au} ± 77] × 102 vs [270 au ± 164] × 102, P = .049]), washout ([15 au ± 11] × 103 vs [65 au ± 38] × 103, P = .020]) and both wash-in and washout ([24 au ± 18] × 103 vs [92 au ± 53] × 103, P = .023). Conclusion Low-flow hypothermic conditions resulted in reduced cerebral perfusion, as measured with transfontanellar contrast-enhanced US, which inversely correlated with age at surgery. Clinical trial registration no. NCT03215628 © RSNA, 2022 Online supplemental material is available for this article.

Hemodynamic evaluation of a new pulsatile blood pump during low flow cardiopulmonary bypass support.

The VentriFlo® True Pulse Pump (VentriFlo, Inc, Pelham, NH, USA) is a new pulsatile blood pump intended for use during short-term circulatory support. The purpose of this study was to evaluate the feasibility of the VentriFlo and compare it to a conventional centrifugal pump (ROTAFLOW, Getinge, Gothenberg, Sweden) in acute pig experiments. Pigs (40-45kg) were supported by cardiopulmonary bypass (CPB) with the VentriFlo (n=9) or ROTAFLOW (n=5) for 6h. Both VentriFlo and ROTAFLOW circuits utilized standard CPB components. We evaluated hemodynamics, blood chemistry, gas analysis, plasma hemoglobin, and microcirculation at the groin skin with computer-assisted video microscopy (Optilia, Sollentuna, Sweden). Pigs were successfully supported by CPB for 6h without any pump-related complications in either group. The VentriFlo delivered an average stroke volume of 29.2±4.8ml. VentriFlo delivered significantly higher pulse pressure (29.1±7.2mmHg vs. 4.4±7.0mmHg, p<0.01) as measured in the carotid artery, with mean aortic pressure and pump flow comparable with those in ROTAFLOW. In blood gas analysis, arterial pH was significantly lower after five hours support in the VentriFlo group (7.30±0.07 vs. 7.43±0.03, p=0.001). There was no significant difference in plasma hemoglobin level in both groups after six hours of CPB support. In microcirculatory assessment, VentriFlo tended to keep normal capillary flow, but it was not statistically significant. VentriFlo-supported pigs showed comparable hemodynamic parameters with significantly higher pulse pressure compared to ROTAFLOW without hemolysis.

Pseudoaneurysm following a neonatal coarctation repair; a dreadful complication.

Aneurysms of descending thoracic aorta following surgical repair of coarctation have been reported in literature. Almost always, they are seen in repairs involving prosthetic patch aortoplasty. We report a neonate who underwent resection and an extended end to end anastomosis repair of coarctation and subsequently developed a huge pseudoaneurysm at a 3-month follow-up. He underwent a repair of the same through a sternotomy approach under hypothermic low flow cardiopulmonary bypass. An autologous pericardial patch aortoplasty was done successfully.

Open-heart techniques and mitral valve plasty for mitral regurgitation in toy- and small-breed dogs: A review

In human medicine, in the past, open-heart techniques for low-bodyweight children and newborn babies with congenital heart disease were more difficult than high-bodyweight adults. In toy- and small-breed dogs with mitral regurgitation (MR), an acquired heart disease, these techniques are more difficult to perform than for congenital heart diseases in young medium-sized or large dogs because of old age and low body weight. Therefore, improved open-heart techniques and mitral valve surgery for severe MR in older toy- and small-breed dogs are essential. Through our surface-cooling hypothermia (sHT) studies, we designed a new, improved open-heart method, namely, “the low-flow cardiopulmonary bypass (CPB) combined with deep sHT in toy- and small-breed dogs (Japan method)”; sHT was later replaced by blood-cooling hypothermia (bHT). At the same time, we devised a new, improved mitral valve plasty (MVP) applicable to severe MR, instead of mitral valve replacement, in toy- and small-breed dogs. This MVP technique was combined with artificial chordal reconstruction, semi-circular suture annuloplasty (AP), and direct scallop-suture valvuloplasty. These MVP techniques are simple, durable, and lead to good long-term quality of life in toy- and small-breed dogs. This review highlights the benefits of our improved CPB and MVP techniques (Japan method) for severe MR in toy-and small-breed dogs, which have led to a high success rate for MVP in severe clinical MR cases in Japan. It may further contribute to the development of more robust techniques for MR in toy- and small-breed dogs. This also represents the first comprehensive review of the history of open-heart surgery, CPB techniques, and MVP methods for MR in toy- and small-breed dogs.

Cerebral blood flow measured by positron emission tomography during normothermic cardiopulmonary bypass: an experimental porcine study.

Mean arterial blood pressure (MAP) and/or pump flow during normothermic cardiopulmonary bypass (CPB) are the most important factors of cerebral perfusion. The aim of this study was to explore the influence of CPB blood flow on cerebral blood flow (CBF) measured by dynamic positron emission tomography (PET) using 15O-labelled water with no pharmacological interventions to maintain the MAP. Eight pigs (69-71 kg) were connected to normothermic CPB. After 60 minutes (min) with a CPB pump flow of 60 mL/kg/min, the pigs were changed to either 35 mL/kg/min or 47.5 mL/kg/min for 60 min and, thereafter, all the pigs returned to 60 mL/kg/min for another 60 min. The MAP was measured continuously and the CBF was measured by positron emission tomography (PET) during spontaneous circulation and at each CPB pump flow after 30 min of steady state. Two pigs were excluded due to complications. CBF increased from spontaneous circulation to a CPB pump flow of 60 mL/kg/min. A reduction in CPB pump flow to 47.5 mL/kg/min (n=3) resulted in only minor changes in CBF while a reduction to 35 mL/kg/min (n=3) caused a pronounced change (correlation coefficient (R2) 0.56). A return of CPB pump flow to 60 mL/kg/min was followed by an increase in CBF, except in the one pig with the lowest CBF during low flow (R2=0.44). CBF and MAP were not correlated (R2=0.20). In this experimental porcine study, a relationship was observed between pump flow and CBF under normothermic low-flow CPB. The effect of low pump flow on MAP showed substantial variations, with no correlation between CBF and MAP.

Microvascular fluid exchange during CPB with deep hypothermia circulatory arrest or low flow.

Use of deep hypothermic low-flow (DHLF) cardiopulmonary bypass (CPB) has been associated with higher fluid loading than the use of deep hypothermia circulatory arrest (DHCA). We evaluated whether these perfusion strategies influenced fluid extravasation rates and edema generation differently per-operatively. Twelve anesthetized pigs, randomly allocated to DHLF (n = 6) or DHCA (n = 6), underwent 2.5 hours CPB with cooling to 20°C for 30 minutes (min), followed by 30 min arrested circulation (DHCA) or 30 min low-flow circulation (DHLF) before 90 min rewarming to normothermia. Perfusion of tissues, fluid requirements, plasma volumes, colloid osmotic pressures and total tissue water contents were recorded and fluid extravasation rates calculated. During the experiments, cerebral microdialysis was performed in both groups. Microvascular fluid homeostasis was similar in both groups, with no between-group differences, reflected by similar fluid extravasation rates, plasma colloid osmotic pressures and total tissue water contents. Although extravasation rates increased dramatically from 0.10 (0.11) ml/kg/min (mean with standard deviation in parentheses) and 0.16 (0.02) ml/kg/min to 1.28 (0.58) ml/kg/min and 1.06 (0.41) ml/kg/min (DHCA and DHLF, respectively) after the initiation of CPB, fluid filtrations during both cardiac arrest and low flow were modest and close to baseline values. Cerebral microdialysis indicated anaerobic metabolism and ischemic brain injury in the DHCA group. No differences in microvascular fluid exchange could be demonstrated as a direct effect of DHCA compared with DHLF. Thirty minutes of DHCA was associated with anaerobic cerebral metabolism and possible brain injury.

Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.

ObjectiveInfants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF). This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.MethodsEighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6), the control group (Group C, n = 6), and the sham operation group (Group S, n = 6), and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG) from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.ResultsThe expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation.ConclusionsHLF cardiopulmonary bypass surgery could intensify systemic inflammatory responses and oxidative stress on infant piglets, thus causing acute kidney injury. Ulinastatin might reduce such inflammatory response and oxidative stress and the extent of kidney injury.

Neurologic and psycho-intellectual outcome related to structural brain imaging in adolescents and young adults after neonatal arterial switch operation for transposition of the great arteries

We studied brain structure abnormalities in adolescents and young adults who had undergone the neonatal arterial switch operation for transposition of the great arteries and related them to the neurologic and psycho-intellectual outcomes. In a prospective longitudinal study, 60 unselected adolescents and young adults who had undergone surgery with combined deep hypothermic circulatory arrest and low flow cardiopulmonary bypass were re-evaluated at a mean age of 16.9±1.7 years to determine their clinical neurologic status, intellectual development, and psychological condition. The results were related to population norms and anatomic structural abnormalities assessed by brain magnetic resonance imaging, with consideration of the risk factors in the preoperative and perioperative periods. Neurologic impairment was more frequent (10%) than in the normal population. Although the average full-scale, verbal, and performance intelligence quotients were not reduced, scores>2 standard deviations less than the expected mean were increased. Above average scores were found for analytical thinking, but the orthography testing results were reduced. The self-rated psychological condition was better than expected. Magnetic resonance imaging demonstrated moderate or severe structural brain abnormalities in 32% of the patients. Periventricular leukomalacia was detected in >50%; its severity correlated with the grade of neurologic impairment, which correlated significantly with reduced intelligence, analytical thinking, and orthography. Preoperative acidosis and hypoxia were the only independent patient-related risk factors for neurologic dysfunction, reduced intelligence, periventricular leukomalacia, and reduced brain volume. Despite encouraging overall neurodevelopmental outcomes, a significant minority had performances below the expected level, emphasizing the need for ongoing surveillance. Considering the high frequency of structural brain abnormalities, prospective long-term studies are needed to define their prognostic value with respect to the neuropsychological outcomes in childhood and adolescence.

Effects of pulmonary artery perfusion with urinary trypsin inhibitor as a lung protective strategy under hypothermic low-flow cardiopulmonary bypass in an infant piglet model

This study aimed to evaluate the effects of pulmonary artery perfusion with a urinary trypsin inhibitor (UTI) as a lung protective strategy in order to provide an experimental basis for immature lung clinical protective strategies on deep hypothermia with low-flow (DHLF) cardiopulmonary bypass (CPB)-induced pulmonary injury in an infant piglet model. The piglets (n=15), aged 18.7±0.3 days, weight 4.48±0.21kg, were randomly divided into 3 groups, with 5 piglets in each group: the control group, the pulmonary artery perfusion without UTI group (Group P) and the pulmonary artery perfusion with UTI group (Group U). The levels of the cytokines tumour necrosis factor-α, myeloperoxidase, malondialdehyde and interleukin-10 (TNF-α, MPO, MDA and IL-10) in pulmonary venous serum and lung tissue and the activity of NF-kappa B in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA) and electrophoresis mobility shift assay (EMSA), respectively. After DHLF-CPB, all of the piglets demonstrated a state of lung injury as a deterioration of lung function indices, lung injury scores, pulmonary ultrastructure changes, expression of TNF-α, MPO, MDA and IL-10 and the activities of nuclear factor-kappa B (NF-κB), while pulmonary artery perfusion with UTI significantly ameliorated lung function and histopathological changes, with greatly decreased serum levels of TNF-α and MPO compared to the other two groups. Also, we found an increase in the level of IL-10 in Group U lungs compared with that in Group P lungs, which correlated with a strong inhibition in the activity of NF-κB. Pulmonary artery perfusion with UTI ameliorated the DHLF-induced immature pulmonary injury in the lungs via a reduction of pro-inflammatory cytokine expression and up-regulated levels of IL-10 by inhibiting the activity of NF-κB.

Modified single innominate artery cannulation with low flow cardiopulmonary bypass during repair of interrupted aortic arch

Results Age at time of surgery was 7 days (4-120 days) and weight 3.1 kg (2.1 to 5.8 kg). Selective cerebral perfusion was maintained in all patients throughout aortic reconstruction. During the period of selective cerebral perfusion, pump flow rate was maintained at 30 mls/kg/min. Aortic cross clamp time, low-flow, and total CPB time were 66 (42-114), 29 (18-41) and 109 (83-217) minutes, respectively. There were no deaths or neurological injury in this series. Postoperative ventilation time, and length of ICU and hospital stay were 3 (2-14), 5 (3-21), and 13 (6-27) days, respectively. Follow-up, complete at 48 months (21-156), revealed no late neurologic sequelae nor innominate artery complications. There were three late re-stenosis of the aortic arch requiring balloon dilatation in 2 and surgical repair in 1.

A Stepwise Aortic Clamp Procedure to Treat Porcelain Aorta Associated with Aortic Valve Stenosis and Hemodialysis

A 62-year-old man was referred for an aortic-valve surgery because of severe aortic stenosis. Thirty years ago, he had undergone a mitral valve commissurotomy and after 9 years, the valve had been replaced by a mechanical valve. He had been undergoing hemodialysis for the past 8 years. A computed tomographic (CT) scan of the chest and abdomen showed a dense circumferential calcification in the wall of the entire thoracic and abdominal aorta, pulmonary artery, and left and right atrium. A conventional aortic-valve replacement was performed. To avoid an embolic event, a "stepwise aortic clamp" procedure was attempted and involved the following: (1) brief circulatory arrest and aortotomy during moderate hypothermia; (2) balloon occlusion at the ascending aorta during low-flow cardiopulmonary bypass (CPB); (3) endoarterectomy by using an ultrasonic surgical aspirator to enable aortic cross-clamping; and (4) a cross-clamp reinforced with felt and full-flow CPB. The patient recovered without any thromboembolic events. Using this procedure to treat a porcelain aorta seemed to reduce the time limit and reduced the risk of brain injury during cardiac surgery.

Invited Commentary

Fabiani and colleagues [1Fabiani J.-N. Raux M. Alsac J.-M. et al.Deep hypothermia and low flow for surgery for abdominal or extraperitoneal tumors with cavoatrial extension.Ann Thorac Surgery. 2013; 95: 2036-2041Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar] report the removal of tumor thrombus into the inferior vena cava (IVC) by use of deep hypothermic low-flow cardiopulmonary bypass (CPB). There was no mortality at the 1-year follow-up of these patients. The authors conclude that this technique allows for safe and complete removal of tumor thrombus into the IVC while providing organ protection. It is not clear whether the authors placed an IVC filter when the IVC was partially obstructed at the end of the operation to avoid pulmonary emboli. Perhaps the only limitation of this report is the limited number of patients, making it difficult to standardize the surgical approach for removal of these tumors. The prevalence of patients with extensive IVC tumor thrombus is very low. However, the surgical procedure is associated with high morbidity and mortality (over 8%) when deep hypothermic circulatory arrest is used [2Shuch B. Crispen P.L. Leibovich B.C. et al.Cardiopulmonary bypass and renal cell carcinoma with level IV tumor thrombus: can deep hypothermic circulatory arrest limit perioperative mortality?.BJU Int. 2010; 107: 724-728Crossref Scopus (42) Google Scholar]. This underscores the importance of the experience of the surgical team performing the operation. Some centers, such as ours, have gone to great lengths to avoid CPB altogether, using innovative technical maneuvers [3Ciancio G. Gonzalez J. Shirodkar S.P. Angulo J.C. Soloway M.S. Liver transplantation techniques for the surgical management of renal cell carcinoma with tumor thrombus in the inferior vena cava: step-by-step description.Eur Urol. 2010; 59: 401-406Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar, 4Ciancio G. Shirodkar S.P. Soloway M.S. Livingstone A.S. Barron M. Salerno T.A. Renal carcinoma with supradiaphragmatic tumor thrombus: avoiding sternotomy and cardiopulmonary bypass.Ann Thorac Surg. 2010; 89: 505-510Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar]. The best approach for such patients would be to refer them to centers with extensive experience with these complex operations, where the operation can be tailored to the specific location of the tumor, with use of a multidisciplinary surgical team that includes a urologic oncologist, a cardiothoracic surgeon, and an anesthesiologist with expertise in transesophageal echocardiography. It is important to determine the exact extension of the tumor thrombus and involvement of the IVC wall with imaging technology. This helps the surgeons to individualize the approach, the extent of expected surgical procedure, and the need for CPB. These tumors with vascular invasion into the IVC continue to be a challenge to the surgical team. It is clear that complete excision of the tumor, including removal of involved IVC, with negative margins, as described by the authors, allows the best chance for patient survival. Deep Hypothermia and Low Flow for Surgery for Abdominal or Extraperitoneal Tumors With Cavoatrial ExtensionThe Annals of Thoracic SurgeryVol. 95Issue 6PreviewSurgical treatment of retroperitoneal tumors with cavoatrial involvement can be challenging. Completeness of resection of the cava tumor extension is crucial for the patient's survival. We report a monocentric experience with the use of cardiopulmonary bypass and deep hypothermic low flow for the surgical resection of caval and atrial involvement of retroperitoneal tumors. Full-Text PDF

What to expect after repair of total anomalous pulmonary venous connection: data from 193 patients and 2902 patient years†

Total anomalous pulmonary venous connection (TAPVC) occurs as isolated cases, in combination with single ventricle physiology, and may be complicated by pulmonary venous obstruction. We sought to identify potential risk factors for long-term mortality and reoperations. Data from 193 consecutive patients who had undergone repair of TAPVC between 1974 and 2011 were analysed using multivariate Cox regression. Mean follow-up time was 15.0 ± 11.0 years, 95% complete. Survival was 82.7 ± 2.9% at 20 years. Single ventricle physiology (5.9% of the patients, P < 0.001) emerged as the only significant risk factor for mortality in multivariate analyses. Freedom from cardiac reoperation was 82.2 ± 3.3% at 20 years. Single ventricle physiology (P < 0.001) was the only risk factor for cardiac reoperations in multivariate analyses. Freedom from reoperations for pulmonary venous obstruction was 90.4 ± 2.5% at 20 years. An age at operation of ≤30 days (52.8% of the patients, P = 0.007) was the only risk factor for reoperations for pulmonary venous obstruction in univariate analyses. In patients with isolated TAPVC (n = 177), preoperative pulmonary venous obstruction (53.7% of the patients, P = 0.030) and deep hypothermic circulatory arrest (78.5% of the patients, P = 0.017) emerged as risk factors for mortality in univariate analyses. An age at operation of ≤30 days (53.7% of the patients, P = 0.022) was the only risk factor for reoperations for pulmonary venous obstruction in univariate analyses. Survival into the third decade without reoperations is excellent in patients with isolated TAPVC without preoperative pulmonary venous obstruction, irrespective of the type of anomalous connection. In contrast, survival of patients with TAPVC and single ventricle physiology is among the poorest of all congenital heart defects. Reoperations for pulmonary venous obstruction are rare and are predominantly required in patients who were operated on as neonates. Survival may be improved by using a strategy of low-flow cardiopulmonary bypass.

Ulinastatin as a neuroprotective and anti‐inflammatory agent in infant piglets model undergoing surgery on hypothermic low‐flow cardiopulmonary bypass

Infants are potentially more susceptible to brain injury mediated via cell death attributed to cardiopulmonary bypass (CPB) especially with prolonged hypothermic low flow (HLF). We hypothesized that a human urinary protease inhibitor (ulinastatin), by its anti-inflammatory effect, would reduce central nervous system (CNS) injury during HLF. Fifteen general-type infant piglets were randomized to ulinastatin group (group U, n = 5), control group (group C, n = 5), and sham operation group (group S, n = 5). Routine CPB was established after median thoracotomy in group U and C under anesthesia. When the temperature of infant piglets dropped down to 25 °C, low-flow CPB (50 ml·kg(-1) ·min(-1) ) was instituted. After 120 min of aortic cross-clamping and 20- to 30-min rewarming, the aortic cross-clamp was removed and finally the piglet was weaned from CPB. Five thousand units per killogram of ulinastatin and equivalently normal saline were, respectively, given at the beginning of and at aortic declamping in group U and group C. group S just received sham median thoracotomy. Venous blood samples were taken immediately after anesthesia induction in all three groups, 5- and 120-min post CPB in both group U and C, respectively; plasma markers of inflammation and CNS injury were compared. Pathology results of hippocampus were observed by light microscopy. Statistically significant differences between group C and U were noted in the expression of inflammatory markers such as IL-10, TNF-α and neuron-specific enolase at 120-min post CPB. Brain injuries were observed in both groups (index cases and controls) and were milder in group U. In our study, HLF CPB on infant piglets resulted in brain injury, and ulinastatin might reduce the extent of such injury.

Brain injury caused by deep hypothermic low-flow cardiopulmonary bypass surgery, an experimental study on piglets

Objective To evaluate the effect and mechanisms of prolonged deep hypothermic low-flow cardiopulmonary bypass (CPB) cardiac surgery to the immature brain on piglets. Methods 15 Beijing Landrace piglets were divided into study group (n=10) and control group (n=5).Routine CPB was established after median thoracotomy in study group under anesthesia.Lowflow CPB(50 ml·kg-1·min-1)was started when the temperature of the animal dropped down to 25 ℃.The aorta was reopened after 120 min cross-clamping.Brain hippocampus tissues were harvested after 120 min following CPB ceased.In control group,hippocampus tissues were harvested after median thoracotomy under anesthesia.In study group,venous blood samples were taken immediately after anesthesia induction (T1),5 min (T2) and 120 min (T3) after the CPB shutdown,and interleukin (IL)-6,tumor necrosis factor (TNF)-α were tested through enzyme-linked immunosorbent assay(ELISA).In both groups,HE staining for pathological examination of brain hippocampus tissues was adopted; and hippocampus tissues homogenates,contents of neuron-specific enolase (NSE),S100 protein β subtypes (S100β) were detected by ELISA method.Results 1 piglet from study group was died by heart arrest after CPB;the other 9 piglets in study group and all 5 in control group completed to the end of the experiment.In study group,compared with T1,IL-6,TNF-α were increased by 7.01％(P＜0.05),3.52％(P＜0.05)in T2,and by 5.10％(P＜0.05),1.47％(P＞0.05)in T3.Compared with control group,study group showed pathological changes of brain damage,and NSE,S100β were also increased by 40.08％(P＜0.05)、29.66％(P＜0.05). Conclusions Deep hypothermic low-flow CPB would result in brain injury on piglets and its key mechanism might be inflammatory injury. Key words: Hypothermic low-flow; Cardiopulmonary bypass; Cardiac surgery; Brain injury; Piglets

Neurodevelopmental outcomes after congenital heart surgery and strategies for improvement

The present review focuses on neurodevelopmental and neuropsychologic outcomes following neonatal and infant heart surgery for complex congenital heart lesions. The data include recent reports on perioperative MRI and recent results of randomized clinical trials addressing perioperative variables. Advancements in magnetic resonance techniques have reinforced earlier data that newborns with complex congenital heart lesions are frequently born with brain immaturity. Randomized clinical trials have looked at several important perioperative candidate predictors as potential independent risk factors for worsened neurodevelopmental outcomes: no difference was found between regional cerebral perfusion and deep hypothermic circulatory arrest on 1-year outcomes; no difference was found between the modified Blalock-Taussig shunt and the right ventricular to pulmonary artery shunt as part of the Norwood procedure on 14-month outcomes; at 16-year testing for individuals with transposition of the great arteries following the arterial switch operation, no significant difference was found between low-flow cardiopulmonary bypass and deep hypothermic circulatory arrest. Randomized clinical, cross-sectional, and prospective trials have explored robust analyses looking for independent risk factors for worsened neurodevelopmental outcomes. Most of these risk factors are patient-related or socioeconomic, with only a few potentially modifiable.

Effect of granulocyte-colony stimulating factor on expression of selected proteins involved in regulation of apoptosis in the brain of newborn piglets after cardiopulmonary bypass and deep hypothermic circulatory arrest

The study objective was to investigate the effect of granulocyte-colony stimulating factor on the expression of proteins that regulate apoptosis in newborn piglet brain after cardiopulmonary bypass and deep hypothermic circulatory arrest. The newborn piglets were assigned to 3 groups: (1) deep hypothermic circulatory arrest (30 minutes of deep hypothermic circulatory arrest, 1 hour of low-flow cardiopulmonary bypass); (2) deep hypothermic circulatory arrest with prior injection of granulocyte-colony stimulating factor (17 μg/kg 2 hours before cardiopulmonary bypass); and (3) sham-operated. After 2 hours of post-bypass recovery, the frontal cortex, striatum, and hippocampus were dissected. The expression of proteins was measured by gel electrophoresis or protein arrays. Data are presented in arbitrary units. Statistical analysis was performed using 1-way analysis of variance. In the frontal cortex, only Fas ligand expression was significantly lower in the granulocyte-colony stimulating factor group when compared with the deep hypothermic circulatory arrest group. In the hippocampus, granulocyte-colony stimulating factor increased Bcl-2 (54.3 ± 6.4 vs 32.3 ± 2.2, P = .001) and serine/threonine-specific protein kinase (141.4 ± 19 vs 95.9 ± 21.1, P = .047) when compared with deep hypothermic circulatory arrest group. Caspase-3, Bax, Fas, Fas ligand, death receptor 6, and Janus protein tyrosine kinase 2 levels were unchanged. The Bcl-2/Bax ratio was 0.33 for deep hypothermic circulatory arrest group and 0.93 for the granulocyte-colony stimulating factor group (P = .02). In the striatum, when compared with the deep hypothermic circulatory arrest group, the granulocyte-colony stimulating factor group had higher levels of Bcl-2 (50.3 ± 7.4 vs 31.8 ± 3.8, P = .01), serine/threonine-specific protein kinase (132.7 ± 12.3 vs 14 ± 1.34, P = 2.3 × 10(6)), and Janus protein tyrosine kinase 2 (126 ± 17.4 vs 77.9 ± 13.6, P = .011), and lower levels of caspase-3 (12.8 ± 5.0 vs 32.2 ± 11.5, P = .033), Fas (390 ± 31 vs 581 ± 74, P = .038), Fas ligand (20.5 ± 11.5 vs 57.8 ± 15.6, P = .04), and death receptor 6 (57.4 ± 4.4 vs 108.8 ± 13.4, P = .007). The Bcl-2/Bax ratio was 0.25 for deep hypothermic circulatory arrest and 0.44 for the granulocyte-colony stimulating factor groups (P = .046). In the piglet model of hypoxic brain injury, granulocyte-colony stimulating factor decreases proapoptotic signaling, particularly in the striatum.

Staged Resternotomy for a Retrosternal Giant Aneurysm of the Thoracic Aorta Using an Inferior T-Shaped Ministernotomy

We describe a staged resternotomy technique using an inferior T-shaped ministernotomy for three redo cases with a retrosternal aortic arch aneurysm. To minimize the disadvantages of resternotomy during closed-chest hypothermia, an inferior T-shaped ministernotomy was performed before approaching the aneurysm. After establishment of the cardiopulmonary bypass with femoral or axillary arterial cannulation, or both, and right atrial drainage, a venting catheter was inserted into the left ventricle and core cooling was induced at 25°C. The retrosternal aneurysm was then exposed by additional superior sternotomy. Under hypotherma with antegrade cerebral perfusion, the distal side of a four-branched graft was anastomosed. During rewarming, reconstruction of the arch vessels and proximal anastomosis of the branched graft were performed. In the 3 patients operated on using this technique, there were no perioperative deaths or serious complications. This suggests that the technique can be safely performed and minimizes the disadvantages of the widely used resternotomy technique.

Adolescents With d-Transposition of the Great Arteries Corrected With the Arterial Switch Procedure

Background— We report neuropsychological and structural brain imaging assessments in children 16 years of age with d-transposition of the great arteries who underwent the arterial switch operation as infants. Children were randomly assigned to a vital organ support method, deep hypothermia with either total circulatory arrest or continuous low-flow cardiopulmonary bypass. Methods and Results— Of 159 eligible adolescents, 139 (87%) participated. Academic achievement, memory, executive functions, visual-spatial skills, attention, and social cognition were assessed. Few significant treatment group differences were found. The occurrence of seizures in the postoperative period was the medical variable most consistently related to worse outcomes. The scores of both treatment groups tended to be lower than those of the test normative populations, with substantial proportions scoring ≥1 SDs below the expected mean. Although the test scores of most adolescents in this trial cohort are in the average range, a substantial proportion have received remedial academic or behavioral services (65%). Magnetic resonance imaging abnormalities were more frequent in the d-transposition of the great arteries group (33%) than in a referent group (4%). Conclusions— Adolescents with d-transposition of the great arteries who have undergone the arterial switch operation are at increased neurodevelopmental risk. These data suggest that children with congenital heart disease may benefit from ongoing surveillance to identify emerging difficulties. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00000470.