Hypothermic Circulatory Arrest Group Research Articles

Piglet cardiopulmonary bypass induces intestinal dysbiosis and barrier dysfunction associated with systemic inflammation.

The intestinal microbiome is essential to human health and homeostasis, and is implicated in the pathophysiology of disease, including congenital heart disease and cardiac surgery. Improving the microbiome and reducing inflammatory metabolites may reduce systemic inflammation following cardiac surgery with cardiopulmonary bypass (CPB) to expedite recovery post-operatively. Limited research exists in this area and identifying animal models that can replicate changes in the human intestinal microbiome after CPB is necessary. We used a piglet model of CPB with two groups, CPB (n=5) and a control group with mechanical ventilation (n=7), to evaluate changes to the microbiome, intestinal barrier dysfunction and intestinal metabolites with inflammation after CPB. We identified significant changes to the microbiome, barrier dysfunction, intestinal short-chain fatty acids and eicosanoids, and elevated cytokines in the CPB/deep hypothermic circulatory arrest group compared to the control group at just 4 h after intervention. This piglet model of CPB replicates known human changes to intestinal flora and metabolite profiles, and can be used to evaluate gut interventions aimed at reducing downstream inflammation after cardiac surgery with CPB.

Hypothermic circulatory arrest versus aortic clamping in thoracic and thoracoabdominal aortic aneurysm repair.

To compare perioperative and midterm outcomes in thoracic and thoraco-abdominal aortic aneurysm (TAA and TAAA) repair using hypothermic circulatory arrest (HCA) or aortic clamping (AC) with mild hypothermia. From 2012 to 2021 there were 180 open repairs of a TAA or TAAA, of which 90 (50%) were done with HCA and 90 (50%) with aortic clamping with mild hypothermia. The indications for HCA were arch aneurysm, TAA from chronic aortic dissection, and inability to clamp the aorta for proximal anastomosis. Compared to AC, the HCA group had less prior descending aorta replacement/repair (9.1% vs. 32%, p = 0.0001). Intraoperatively, the HCA group had more TAAs (70% vs. 20%, p < 0.0001) while the AC group had more TAAAs (80% vs. 30%, p < 0.0001). HCA group had longer cardiopulmonary bypass times (242 vs. 181 min, p < 0.0001) but shorter cross-clamp time (39 vs. 120 min, p < 0.0001) and lower temperatures (18°C vs. 34°C, p < 0.0001). Postoperatively, the HCA group had longer intubation times (31 vs. 26 h, p = 0.002), but all other postoperative outcomes including paralysis (2.2% vs. 8.9%, p = 0.08), and operative mortality (4.4% vs. 2.2%, p = 0.68) were similar between HCA and AC groups. Patient age was an independent risk factor for postoperative paralysis (OR 1.07, p = 0.03) while HCA was not significant (OR 0.37, p = 0.21). Five-year survival was similar between HCA and AC groups (85% vs. 80%, p = 0.36). Postoperative outcomes and midterm survival were acceptable in thoracic and thoracoabdominal aneurysm patients after HCA or AC. Both HCA and AC with mild hypothermia were valid approaches in TAA/A repair.

Robotic Level IV Inferior Vena Cava Thrombectomy Using an Intrapericardial Control Technique: Is It Safe Without Cardiopulmonary Bypass?

We introduce an intrapericardial control technique using a robotic approach in the surgical treatment of renal tumor with level IV inferior vena cava thrombus to decrease the severe complications associated with cardiopulmonary bypass and deep hypothermic circulatory arrest. Eight patients with level IV inferior vena cava thrombi not extending into the atrium underwent transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy obviating cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass-free group) by an expert team comprising urological, hepatobiliary, and cardiovascular surgeons. The central diaphragm tendon and pericardium were transabdominally dissected until the intrapericardial inferior vena cava were exposed and looped proximal to the cranial end of the thrombi under intraoperative ultrasound guidance. As controls, 14 patients who underwent robot-assisted inferior vena cava thrombectomy with cardiopulmonary bypass (cardiopulmonary bypass group) and 25 patients who underwent open thrombectomy with cardiopulmonary bypass/deep hypothermic circulatory arrest (cardiopulmonary bypass/deep hypothermic circulatory arrest group) were included. Clinicopathological, operative, and survival outcomes were retrospectively analyzed. Eight robot-assisted inferior vena cava thrombectomies were successfully performed without cardiopulmonary bypass, with 1 open conversion. The median operation time and first porta hepatis occlusion time were shorter, and estimated blood loss was lower in the cardiopulmonary bypass-free group as compared to the cardiopulmonary bypass group (540 vs 586.5 minutes, 16.5 vs 38.5. minutes, and 2,050 vs 3,500 mL, respectively). Severe complications (level IV-V) were also lower in the cardiopulmonary bypass-free group than in cardiopulmonary bypass and cardiopulmonary bypass/deep hypothermic circulatory arrest groups (25% vs 50% vs 40%). Oncologic outcomes were comparable among the 3 groups in short-term follow-up. Pure transabdominal-transdiaphragmatic robot-assisted inferior vena cava thrombectomy without cardiopulmonary bypass/deep hypothermic circulatory arrest represents as an alternative minimally invasive approach for selected level IV inferior vena cava thrombi.

Cerebral protection using deep hypothermic circulatory arrest versus retrograde cerebral perfusion for aortic hemiarch reconstruction.

With evolutions in technique, recent data encourage the use of cerebral perfusion during aortic arch repair. However, a randomized data have demonstrated higher rates of neurologic injury according to MRI lesions using antegrade cerebral perfusion during hemiarch reconstruction. This was a retrospective review of two institutional aortic center databases to identify adult patients who underwent aortic hemiarch reconstruction for elective aortic aneurysm or acute type A aortic dissection. Patients were stratified according to cerebral protection method: (1) deep hypothermic circulatory arrest (DHCA)group versus (2) DHCA/retrograde cerebral perfusion (RCP) group. A total of 320 patients and 245 patients underwent hemiarch reconstruction for aortic aneurysm electively and aortic dissection, respectively. In aneurysmal pathology, the DHCA group included 133 patients and the DHCA/RCP group included 187 patients. Operative mortality was 0.8% in the DHCA group and 2.7% in the DHCA/RCP group (p = 0.41). Kaplan-Meier survival estimates revealed comparable 2-year survival (p = 0.14). In dissection, 43 patients and 202 patients were included in the DHCA group and the DHCA/RCP group, respectively. Operative mortality was equivalent between the two groups (11.6% in the DHCA group and 9.4% in the DHCA/RCP group, p = 0.58). Long-term survival was similar at 2 years between the groups (p = 0.06). Multivariable analysis showed cerebral perfusion strategy was not associated with the composite outcome of operative mortality and stroke. In treating both elective and acute ascending aortic pathologies with hemiarch reconstruction, both DHCA alone or in combination with RCP yield comparable results.

Mild hypothermic circulatory arrest with selective cerebral perfusion in open arch surgery.

BackgroundThis study aimed to evaluate whether the use of mild hypothermic circulatory arrest (HCA) with selective cerebral perfusion (SCP) in open arch procedure provides comparable perioperative results to moderate HCA for patients with dissected or degenerative arch pathologies.MethodsBetween January 2017 and September 2020, a total of 88 consecutive patients (mean age 47±11 years, 71 males) underwent open arch repair under a single surgeon at our institution with mild or moderate systemic hypothermia assisted by unilateral or bilateral SCP. Patients were divided into groups according to the nasopharyngeal temperature at the beginning of HCA: a moderate HCA group (n=47, 53.4%) and a mild HCA group (n=41, 46.6%). The postoperative mortality, morbidity, and visceral organ functions between these groups were analyzed retrospectively.ResultsCompared to the moderate HCA group, the mild HCA group had a significantly higher core temperature (nasopharynx: 24.4±0.8 vs. 28.5±2, P<0.001; bladder 25.9±0.9 vs. 30±1.2, P<0.001), and the incidence of major adverse events (MAE) in this group was markedly lower (21.3% vs. 4.9%, P=0.031). No differences were identified between the two groups refer to in-hospital mortality, permanent neurological deficit (PND), temporary neurological deficit (TND), and paraplegia (8.5% vs. 2.4%, P=0.366; 8.5% vs. 0, P=0.120; 6.4% vs. 7.3%, P=1.0; 4.3% vs. 2.4%, P=1.0, respectively). In the moderate HCA group, 6 patients (12.8%) developed acute renal failure needing replacement therapy, which did not occur in the mild HCA group (P=0.028). The duration of ventilator support and intensive care unit stay was shorter in the mild HCA group, as well as a decreased volume of drainage during the first 24 h and reduced platelet transfusion.ConclusionsThe preliminary results of the mild HCA group with SCP applied in open arch repair, mainly in total arch replacement (TAR) and stented elephant trunk (SET) implantation for aortic dissection, were satisfactory. Furthermore, comparable inferior outcomes were obtained with mild HCA compared with that of the conventional moderate HCA strategy. These encouraging surgical and postoperative results favor this more aggressive hypothermia strategy in open arch repair.

Changing of haemostatic system in a pig model during different types of hypothermic circulatory arrest.

Hypothermic circulatory arrest is usually used in aortic surgery, congenital heart defect repairs and other complex surgeries. It is frequently associated with excessive postoperative bleeding and the transfusion of allogeneic blood products. The physiopathology of hypothermic circulatory arrest-induced coagulopathy has never been systematically studied. The aim of the study was to investigate this phenomenon in a pig model. Ten pigs were randomly assigned to 30min of hypothermic circulatory arrest at either 15°C (n=5) or 25°C (n=5). Detection of apoptosis and haemostatic system assays were performed in this experiment. Enzyme-linked immunosorbent assays were performed at ten time points in each group to study the changes in the coagulation system in hypothermic circulatory arrest. All of the statistical analyses were performed in SPSS software, version 18.0, and as bilateral tests, and p<0.05 was considered statistically significant. There was no significant difference in the effect of different types of hypothermic circulatory arrest on routine laboratory tests and tissue sample analysis (p>0.05, for all). Our results demonstrated that more severe systemic activation of the coagulation system (TAT and F1+2) was applied in the deep hypothermic circulatory arrest group but not in the moderate hypothermic circulatory arrest group (TAT/p=0.01, F1+2/p=0.03). However, this activation of the coagulation system (AT III and PC) was not associated with changes in the anticoagulation pathway (AT III/p=0.24, PC/p=0.33). In addition, analysis of biomarkers of the haemostatic system revealed that the consumption of coagulation is more concentrated on extrinsic coagulation factors (FVII/p=0.01). Moderate hypothermic circulatory arrest is more suitable for patients with coagulation dysfunction. We believe the application of deep hypothermic circulatory arrest should pay more attention to changes in coagulation rather than the anticoagulation pathway. Extrinsic coagulation factor supplementation is more effective after deep hypothermic circulatory arrest.

Mild Systemic Hypothermic Circulatory Arrest Using a Frozen Elephant Trunk Graft with Endo-Balloon Occlusion for Total Arch Replacement.

Stroke and paraplegia are serious complications of total aortic arch replacement (TAR). Hypothermic circulatory arrest and cerebral perfusion reduce the risk of neurologic complications, but longer circulatory arrest time remains a risk factor for such complications. We utilized a frozen elephant trunk (FET) with endo-balloon occlusion under mild systemic hypothermia, which allowed us to shorten circulatory arrest time. Between April 2007 and May 2020, 72 patients underwent elective TAR using antegrade cerebral perfusion (ACP). They were divided into 2 groups. 64 patients received conventional TAR with moderate systemic hypothermic (bladder temperature, 25-28°C) circulatory arrest (group C). We used a FET with endo-balloon occlusion and retrograde perfusion through the femoral artery for the newest 8 patients who had mild hypothermic (bladder temperature of 30°C) circulatory arrest (group B). The mean operation time (257.5 ± 42.1 versus 327.8 ± 84.9 min, P = .023), CPB time (144.4 ± 28.1 versus 178.2 ± 26.4 min, P = .003), cardiac arrest time (75.5 ± 21.2 versus 95.7 ± 56.4 min, P < .001), SCP time (100.8 ± 25.5 versus 124 ± 23.2 min, P < .001), lower body circulation arrest time (17.2 ± 4.2 versus 62.5 ± 19.3 min, P < .001) were significantly shorter in the endo-balloon occlusion group. There were no perioperative neurological and renal complications or mortality in FET group. The new technique enabled a decrease in mechanical ventilation time (8.6 ± 1.4 versus 13.9 ± 5.7 min, P = .015) and hospital length of stay (9.7 ± 1.8 versus 18.3 ± 4.6 min, P = .005). FET using an endo-balloon occlusion with mild hypothermia is a safe and an effective approach in TAR.

Renal protective effect of the aortic balloon occlusion technique in total arch replacement with frozen elephant trunk.

Organ dysfunction caused by hypothermic circulatory arrest continues to concern surgeons. The aortic balloon occlusion (ABO) technique can significantly shorten the circulatory arrest time in total arch replacement with frozen elephant trunk (TAR with FET). This study aims to analyze the renal protective effect of the ABO technique and to analyze the predictors of acute kidney injury (AKI) and continuous renal replacement therapy (CRRT) after TAR with FET. Between August 2017 and September 2018, 247 patients who underwent TAR with FET were divided into ABO and moderate hypothermic circulatory arrest (MHCA) groups. The primary endpoint was postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multivariable logistic analysis was used to identify the predictors of AKI and CRRT after TAR with FET. With the application of the ABO technique, the circulatory arrest time was significantly shortened (ABO 4, IQR: 3-6 vs. MHCA 18, IQR: 16-20, P<0.001). Meanwhile, surgeons safely set the lowest nasopharyngeal temperature at a higher grade (ABO 28.1, IQR: 27.4-28.5 vs. MHCA 24.7, IQR: 24.1-25.1, P<0.001). The peak serum creatinine (SCr) values within 48 hours after the surgery was lower in the ABO group than in the MHCA group (ABO 124, IQR: 97-173 vs. MHCA 146, IQR: 108-221, P=0.008). The distribution of AKI grade according to the KDIGO criteria differed between the two groups (P=0.04): more patients in the ABO group were free from AKI (Grade 0) than patients in the MHCA group (33% vs. 23.1%), and the proportion of patients with high-grade AKI (Grades 2 and 3) in the ABO group was lower than that in the MHCA group (21% vs. 32%). The ABO technique was associated with reduced potential for AKI, but was not protective for CRRT. The ABO technique significantly shortened the circulatory arrest time and safely elevated temperature, and provided better renal protection in patients undergoing TAR with FET. The ABO technique did not reverse the need for CRRT, nor did it reduce mortality or major adverse events.

Clinical Assessment of Perfusion Techniques During Surgical Repair of Coarctation of Aorta With Aortic Arch Hypoplasia in Neonates: A Pilot Prospective Randomized Study

We aimed to compare the safety and efficacy of 3 perfusion methods primarily used in aortic arch reconstruction in infants, namely, deep hypothermic circulatory arrest, selective antegrade cerebral perfusion, and double arterial cannulation. Forty-five infants with aortic arch obstruction and biventricular anatomy were enrolled in this pilot prospective study (ClinicalTrials.gov registration number: NCT02835703). Patients were randomly assigned into 3 groups according to the perfusion strategy (deep hypothermic circulatory arrest, n = 15; selective antegrade cerebral perfusion, n = 15; double arterial cannulation, n = 15). The primary composite endpoint was the incidence of adverse events in the early postoperative period (acute kidney injury [KDIGO criteria], new brain magnetic resonance imaging (MRI) findings, and in-hospital mortality). The secondary endpoints were intensive care unit length of stay, vasoactive-inotropic score index, and cardiopulmonary bypass duration. All patients underwent aortic arch reconstruction under cardiopulmonary bypass and were monitored with near-infrared spectroscopy during surgery. No significant differences in the baseline characteristics and cardiopulmonary bypass duration were observed among the groups. The incidence of unfavorable events was lower in the double arterial cannulation group (P = 0.041). Acute kidney injury was observed in 8, 6, and 5 patients from the deep hypothermic circulatory arrest, selective antegrade cerebral perfusion, and double arterial cannulation groups, respectively (P = 0.64). Twelve patients from the deep hypothermic circulatory arrest group had new brain MRI findings (P = 0.019). There were 5 in-hospital deaths with no significant difference among the groups (P = 0.70). The "head" and "lumbar" values on near-infrared spectroscopy during aortic arch reconstruction were significantly higher in the selective antegrade cerebral perfusion and double arterial cannulation groups than in the deep hypothermic circulatory arrest group. Patients in the double arterial cannulation group had a significantly lower vasoactive-inotropic score index 24 hours postoperatively than the deep hypothermic circulatory arrest group (P = 0.03). Vasoactive-inotropic score index >12 was found to be a risk factor for acute kidney injury and early mortality. Continuous regional perfusion during aortic arch reconstruction decreases the risk of new brain MRI findings in infants and the need for postoperative inotropic support. Although values of near-infrared spectroscopy during the procedure were significantly higher with continuous perfusion strategies, these methods do not reduce the acute kidney injury incidence compared to that with deep hypothermic circulatory arrest. Double arterial cannulation significantly reduces the need for inotropic support.

A novel target to reduce microglial inflammation and neuronal damage after deep hypothermic circulatory arrest

BackgroundNeuroinflammation acts as a contributor to neurologic deficits after deep hypothermic circulatory arrest. However, the molecular mechanism remains unclear. This study postulates that cold-inducible RNA-binding protein can promote deep hypothermic circulatory arrest–induced neuroinflammation. MethodsRats were randomly assigned into 3 groups (n = 5, each group): sham group, deep hypothermic circulatory arrest group, and deep hypothermic circulatory arrest + Cirp−/− group (Cirp−/− group). Murine microglial BV2 cells were administered by adeno-associated viral vectors containing cold-inducible RNA-binding protein small interference RNA or negative control small interference RNA at 2 days before 4-hour oxygen–glucose deprivation at 18°C. Microglial activation, cell death, neuroinflammation, and related protein expression were assessed in tissue samples and cell cultures. ResultsCold-inducible RNA-binding protein was elevated along with evident neuroinflammation and neuronal damage in rats exposed to deep hypothermic circulatory arrest. In Cirp−/− rats, histologic injury (3.00 [interquartile range, 2.00-3.00] vs 1.00 [interquartile range, 1.00-1.50] neuropathological score, P < .001) and microglial activation (40 ± 4 vs 13 ± 7 CA1 area, P < .001) were alleviated after deep hypothermic circulatory arrest. With RNA-sequencing analysis, this associated with reduction of key proinflammatory cytokines induced by inhibiting Brd2-NF-κB signals. In BV2 cells treated with small interference RNA-cold-inducible RNA-binding protein, similar protective effects were observed, including decreased proinflammatory cytokines and cytotoxicity. Brd2-NF-κB signals were confirmed by the addition of Brd2 inhibitor JQ1. Notably, the conditioned medium from BV2 cells transfected with small interference RNA cold-inducible RNA-binding protein significantly reduced apoptosis in neural SH-SY5Y cells after oxygen–glucose deprivation, which was similar to that after JQ1 administration. ConclusionsEnhanced cold-inducible RNA-binding protein in microglia aggravates neuronal injury by promoting the release of proinflammatory cytokines, which might be mediated through Brd2-NF-κB signals during deep hypothermic circulatory arrest.

Moderate Hypothermic Circulatory Arrest Is Preferable During Cardiopulmonary Bypass.

The effect of temperature on cerebral injury during hypothermic circulatory arrest (HCA) has never been specifically studied. This study aimed to compare the effects of two different temperatures used for HCA on the degree of brain injury in pig models. Thirteen pigs were randomly assigned to a deep hypothermic circulatory arrest (DHCA) group (n = 5), moderate hypothermic circulatory arrest (MHCA) group (n = 5), or control group (n = 3). No significant differences in immunohistochemical assay results, including Bax, Bcl-2, and Caspase 3 staining, and a TUNEL assay, were observed between the DHCA and MHCA groups. Furthermore, no significant difference was found for biomarkers of brain injury (Soluble protein-100B) between the two experimental groups. Similarly, no significant difference was observed in the trend of changes in inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-2, and IL-6, between the two groups (p > 0.05). However, coagulation factors, including FXI and FVII, were different between the DHCA and MHCA groups (p < 0.05). Therefore, it can be concluded that MHCA does not increase the risk of cerebral injury. Considering the adverse effects of DHCA on the coagulation system, MHCA is more suitable for current clinical practice.

Deep Hypothermic Circulatory Arrest Does Not Show Better Protection for Vital Organs Compared with Moderate Hypothermic Circulatory Arrest in Pig Model.

Background Continued debates exist regarding the optimal temperature during hypothermic circulatory arrest in aortic arch repair for patients with type A aortic dissection. This study seeks to examine whether the use of moderate hypothermic circulatory arrest in a pig model provides comparable vital organ protection outcomes to the use of deep hypothermic circulatory arrest. Methods Thirteen pigs were randomly assigned to 30 minutes of hypothermic circulatory arrest without cerebral perfusion at 15°C (n = 5), 25°C (n = 5), and a control group (n = 3). The changes in standard laboratory tests and capacity for protection against apoptosis in different vital organs were monitored with different temperatures of hypothermic circulatory arrest management in pig model to determine which temperature was optimal for hypothermic circulatory arrest. Results There were no significant differences in the capacity for protection against apoptosis in vital organs between 2 groups (p > 0.05, respectively). Compared with the moderate hypothermic circulatory arrest group, the deep hypothermic circulatory arrest group had no significant advantages in terms of the biologic parameters of any other organs (p > 0.05). Conclusions Compared with deep hypothermic circulatory arrest, moderate hypothermic circulatory arrest is a moderate technique that has similar advantages with regard to the levels of biomarkers of injury and capacity for protection against apoptosis in vital organs.

Transcriptome profiling reveals activation of inflammation and apoptosis in the neonatal striatum after deep hypothermic circulatory arrest

ObjectivesBrain injury, leading to long-term neurodevelopmental deficits, is a major complication in neonates undergoing cardiac surgeries. Because the striatum is one of the most vulnerable brain regions, we used mRNA sequencing to unbiasedly identify transcriptional changes in the striatum after cardiopulmonary bypass and associated deep hypothermic circulatory arrest. MethodsPiglets were subjected to cardiopulmonary bypass with deep hypothermic circulatory arrest at 18°C for 30 minutes and then recovered for 6 hours. mRNA sequencing was performed to compare changes in gene expression between the striatums of sham control and deep hypothermic circulatory arrest brains. ResultsWe found 124 significantly upregulated genes and 74 significantly downregulated genes in the striatums of the deep hypothermic circulatory arrest group compared with the sham controls. Pathway enrichment analysis demonstrated that inflammation and apoptosis were the strongest pathways activated after surgery. Chemokines CXCL9, CXCL10, and CCL2 were the top upregulated genes with 32.4-fold, 22.2-fold, and 17.6-fold increased expression, respectively, in the deep hypothermic circulatory arrest group compared with sham controls. Concomitantly, genes involved in cell proliferation, cell-cell adhesion, and structural integrity were significantly downregulated in the deep hypothermic circulatory arrest group. Analysis of promoter regions of all upregulated genes revealed over-representation of nuclear factor-kB transcription factor binding sites. ConclusionsOur study provides a comprehensive view of global transcriptional changes in the striatum after deep hypothermic circulatory arrest and found strong activation of both inflammatory and apoptotic signaling pathways in the deep hypothermic circulatory arrest group. Nuclear factor-kB, a key driver of inflammation, appears to be an upstream regulator of the majority of the upregulated genes; hence, nuclear factor-kB inhibitors could potentially be tested for beneficial effects on neurologic outcome.

Normothermic iliac perfusion improves early outcomes after thoraco-abdominal aortic aneurysm repair.

The aim of this study is to evaluate the safety and efficacy of thoraco-abdominal aortic aneurysm repair with normothermic iliac perfusion. One hundred and ninety patients who underwent aortic replacement for the Crawford type II thoraco-abdominal aortic aneurysm between January 2005 and June 2017 were assigned to 2 groups: normothermic iliac perfusion (group A, n = 75) and deep hypothermic circulatory arrest (group B, n = 115). We selected 58 pairs of patients for propensity score matching. We analysed early operative death, a composite of complications and mid-term survival. After propensity score matching, no early operative death occurred in group A (0.0%), and group B had 4 cases of early operative death (6.9%), with a statistically significant difference (P = 0.047). The composite of complications was reported in 11 patients in group A (21.0%) and in 21 patients in group B (36.2%) (P = 0.038). Age >50 years [odds ratio (OR) 6.50, 95% confidence interval (CI) 2.32-16.36; P = 0.020], deep hypothermia (OR 12.13, 95% CI 1.64-23.13; P = 0.003) and chronic renal insufficiency (OR 8.21, 95% CI 2.34-43.33; P < 0.001) were independent risk factors for early operative death. The 3-year, 5-year and 7-year survival rates were 98.3%, 98.3% and 86.9% in group A and 86.9%, 86.9% and 86.9% in group B, respectively (P = 0.471). The 7-year cumulative incidence function rates for reintervention were 0.026% in group A and 0.048% in group B (P = 0.625). Normothermic iliac perfusion provides a viable alternative for thoraco-abdominal aortic aneurysm repair, which reduced early operative death and composited complications.

Role of Moderate Hypothermia and Antegrade Cerebral Perfusion during Repair of Type A Aortic Dissection.

The goal of this study was to compare early postoperative outcomes and actuarial survival between patients who underwent repair of acute type A aortic dissection with deep or moderate hypothermia. A total of 132 consecutive patients from a single academic medical center underwent repair of acute type A aortic dissection between January 2000 and June 2014. Of those, 105 patients were repaired under deep hypothermia (< 24 C°), while 27 patients were repaired under moderate hypothermia (≥24 C°). Median ages were 62 years (range: 27-86) and 59 years (range: 35-83) for patients repaired under deep hypothermia compared with patients repaired under moderate hypothermia, respectively ( p = 0.451). Major morbidity, operative mortality, and 10-year actuarial survival were compared between groups. Operative mortality was 17.1 and 7.4% in the deep and moderate hypothermia groups, respectively ( p = 0.208). Incidence of permanent stroke was 12.4% in the deep hypothermic circulatory arrest group and 0% in the moderate hypothermia group ( p = 0.054). Actuarial 5- and 10-year survival demonstrated a trend for lower long-term mortality with moderate hypothermia compared with deep hypothermia (69% 5-year and 54% 10-year for deep hypothermia vs. 79% 5-year and 10-year for moderate hypothermia, log-rank p = 0.161). Moderate hypothermia is a safe and efficient alternative to deep hypothermia and may have protective benefits. Stroke rate was lower with moderate hypothermia.

Protection of the rat brain from hypothermic circulatory arrest injury by a chipmunk protein

ObjectivesThe study objectives were to test the hypothesis that special protein exists in hibernating chipmunk albumin and whether this protein has a neuroprotective effect in Sprague–Dawley rats during deep hypothermia circulatory arrest. MethodsForty chipmunks were allocated into a hibernation group and an active group (20 chipmunks in each group). Special protein was detected and isolated from hibernating chipmunk albumin. Forty Sprague–Dawley rats were randomly divided into a sham group, deep hypothermia circulatory arrest group, special protein group, and naloxone group (10 rats in each group). Special protein that was detected and collected from hibernating chipmunks were injected in rats in the special protein group for 3 consecutive days before operation, and naloxone was given at the same time in the naloxone group. Rats were subjected to cardiopulmonary bypass and 60-minute deep hypothermia circulatory arrest. Tumor necrosis factor-α and interleukin-6 levels were detected. Animals received neurologic testing. Relative protein expression, malondialdehyde, and superoxide dismutase of hippocampus were detected. The brain was fixed for histopathologic assessment. ResultsThe rats that received special protein displayed ischemic tolerance after deep hypothermia circulatory arrest. The neuroprotective effect could be reversed by naloxone. The inflammation response was attenuated in the special protein group (P < .008, compared with the deep hypothermia circulatory arrest and naloxone groups). The mature brain-derived neurotrophic factor and SIRT1 levels were higher in the special protein group (P < .01, compared with the deep hypothermia circulatory arrest and naloxone groups). Histopathologic assessment showed that the injury in the special protein group was attenuated (pathological score, P < .05; surviving hippocampal CA1 neurons, P < .01; TUNEL-positive neurons, P < .01; compared with deep hypothermia circulatory arrest and naloxone groups). Intravenous injection of special protein significantly improved neurologic recovery. ConclusionsWe found that a specific protein existed in hibernating chipmunk albumin and could play an important neuroprotective role in rats.

The Use of Hypothermic Circulatory Arrest During Heart Transplantation Does Not Worsen Posttransplant Survival

Hypothermic circulatory arrest (HCA) has been used as an adjunct to cardiopulmonary bypass for decades, both electively and emergently, to facilitate a bloodless operative field while maintaining cerebral protection. The aim of this study is to determine the impact of HCA during heart transplantation on posttransplant outcomes. All adult patients undergoing orthotopic heart transplantation at our institution between 2000 and 2012 were retrospectively reviewed. Patients were stratified based on need for HCA during surgery; patients who required HCA (HCA group, n= 25), and patients who did not (no-HCA group, n= 903). The primary outcomes of interest were 30-day and 1-year mortality and postoperative complication rate. Indications for HCA included control of significant hemorrhage (n= 9), need for distal aortic procedures (n= 9), or as an aid in difficult mediastinal dissection (n= 7). Mean duration of HCA was 22± 18 minutes at a mean temperature of 24.5° ± 5.5°C. Significantly more patients in the HCA group underwent transplant for congenital heart disease (16.0% HCA versus 2.8% no-HCA, p= 0.006), and patients in the HCA group had undergone more prior sternotomies (HCA 1 [interquartile range: 1 to 2] versus no-HCA 1 [interquartile range: 0 to 1], p < 0.001]. There was no statistical difference in 30-day mortality (8.0% HCA versus 4.2% no-HCA, p= 0.29) or 1-year mortality (8.0%HCA versus 12.3% no-HCA, p= 0.76). The HCA group had higher rates of reoperation for mediastinal bleeding and postoperative respiratory failure. The need for HCA during heart transplantation is rare but, when required, it is frequently a life-saving adjunct to cardiopulmonary bypass. However, patients who require HCA have higher rates of postoperative complications. Risk factors for needing HCA during transplantation include congenital heart disease and more than one prior sternotomies.

Observations of retinal vessels during intermittent pressure-augmented retrograde cerebral perfusion in clinical cases.

Retrograde cerebral perfusion (RCP) has been used as a cerebroprotective method under hypothermic circulatory arrest (HCA) during aortic surgery. As reported in an animal model in 2005, intermittent pressure-augmented-RCP (IPA-RCP) provides more effective cerebral perfusion than RCP. In 2013, the clinical efficacy of IPA-RCP was described in terms of clinical outcomes and regional cerebral oxygen saturation using infrared spectroscopy. However, the state of cerebral microcirculation during IPA-RCP has not been investigated in humans. The aim of the present study was to investigate cerebral microcirculation during IPA-RCP in humans by assessing the retinal vessels. Between 2013 and 2014, 8 consecutive patients underwent elective total replacement of the aortic arch for true thoracic aortic aneurysms. The IPA-RCP protocol consisted of a continuous venous pressure that was intermittently augmented at 45 mmHg for 30 s and then decreased to 20 mmHg for 120 s after isolated HCA for 300 s. The retinal vessels were assessed via non-invasive direct visualization of the cerebral microcirculation using a fundus camera. Assessments were done before cardiopulmonary bypass, during isolated HCA, and during IPA-RCP at 20 and 45 mmHg. Ratio of the diameter of retinal vessels to that of the optic disc was calculated from the diameters of the retinal arteries, veins and optic disc at each time point and was statistically examined. There were no neurological deficits and mortality. When compared with the control group and both IPA-RCP groups, the retinal vessels in the isolated HCA group were collapsed and the peripheral retinal vessels could not be clearly observed. The RVR was significantly larger in the control group and in both IPA-RCP groups when compared with the isolated HCA group. The RVR of the control group was similar to that of both IPA-RCP groups with regard to the retinal arteries and veins. The RVR of IPA-RCP at 45 mmHg was significantly larger than that at 20 mmHg with regard to the retinal veins. Our study suggested that intermittently augmented venous pressure at 45 mmHg opened the cerebrovenous vessels and enabled adequate cerebral perfusion. IPA-RCP may provide more effective cerebral perfusion under HCA in humans.

Abstract 18378: Comparsion of Cerebral Protection Strategies on Immediate And Longterm Outcome of Patients With Stanford Type a Aortic Dissection

Introduction: The optimal protection strategy for use during acute type A aortic dissection surgery is controversial. Hypothesis: To assess the efficacy and immediate and long-term results of different cerebral protection techniques in the treatment of acute type A aortic dissection. Methods: Between April 1987 and January 2015, 400 patients (270 male patients; mean age 58 years; range 15-88) with acute type A dissection underwent surgical aortic repair with an open distal anastomosis. Either hypothermic circulatory arrest alone at 18 °C (n = 111; 28%) or combined with retrograde cerebral perfusion (n = 117; 29%) or antegrade cerebral perfusion at 25 °C (n = 172; 43%) was used for cerebral protection. Results: The median circulatory arrest time was 35 minutes. The overall 30-day mortality was 16% (63 of 400). The 30-day mortality stratified by group was 20% (22 patients) in the hypothermic circulatory arrest group, 17% in the retrograde cerebral perfusion group (20 patients), and 12% (21 patients) in the antegrade cerebral perfusion group (P = .021). Permanent neurologic dysfunction occurred in 53 patients (14%), with statistically significant differences among the 3 groups (25% for hypothermic circulatory arrest, 13% for retrograde cerebral perfusion, and 7% for antegrade cerebral perfusion; P = 0.01). Univariate analysis showed a significant effect of the cerebral protection strategies on 30-day mortality and neurologic outcome. Kaplan-Meier analysis showed differences among the 3 groups with a 1-, 2-, and 5-year survival rate of 85%, 82%, and 77% with antegrade cerebral perfusion, 75%, 72%, and 66% with retrograde cerebral perfusion, and 65%, 64%, and 62% with hypothermic circulatory arrest alone (p=0.19). Conclusion: Antegrade cerebral perfusion group had a superior 30 day as well as midterm survival and inferior rate of PND. During the study period, several significant improvements in surgical as well anaesthesiological in treatment and management of acute type A aortic dissection were achieved. However, postoperative outcome of patients with type A dissection is multifactorial and independent predictors of mortality and permanent neurologic dysfunction were difficult to identify

Inhibition of microRNA-29c protects the brain in a rat model of prolonged hypothermic circulatory arrest

ObjectiveWe sought to investigate the cerebroprotection of a novel microRNA mechanism by targeting peroxisome proliferator-activated receptor gamma coactivator 1-alpha in a rat model of prolonged deep hypothermia circulatory arrest. MethodsThe right carotid artery and jugular vein of male Sprague–Dawley rats were cannulated for cardiopulmonary bypass. Circulatory arrest was conducted for 60 minutes when the pericranial temperature was cooled to 18°C. The sham group received the surgical procedure without cardiopulmonary bypass and deep hypothermia circulatory arrest; the deep hypothermia circulatory arrest group received cardiopulmonary bypass and deep hypothermia circulatory arrest; lentivirus control vector or lentiviral vector containing antagomiR-29c was given to the deep hypothermia circulatory arrest + vector group or the deep hypothermia circulatory arrest + antagomiR-29c group by intracerebroventricular administration 5 days before cardiopulmonary bypass (n = 8, for each of the 4 groups). Neurologic function was evaluated by the modified hole board test and beam balance task during 14 postoperative days. Expressions of caspase-3, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, and miR-29c in the hippocampus were measured by Western blot and quantitative reverse transcription polymerase chain reaction. Malondialdehyde was measured using the Malondialdehyde Assay Kit (Beyotime, Jiangsu, China). ResultsPretreatment with antagomiR-29c significantly decreased the expression of microRNA-29c and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha in the hippocampus (P < .05 vs deep hypothermia circulatory arrest group). The level of malondialdehyde in the hippocampus was lower in the deep hypothermia circulatory arrest + antagomiR-29c group (P < .05 vs deep hypothermia circulatory arrest group). The neurologic functions were markedly protected in rats pretreated with antagomiR-29c as evidenced by improvement of vestibulomotor and cognitive performance during the early postoperative period. In the deep hypothermia circulatory arrest + antagomiR-29c group, histologic scores of the hippocampus were improved and the level of caspase-3 in the hippocampus was lower (P < .05 vs deep hypothermia circulatory arrest group). ConclusionsInhibition of miR-29c attenuates neurologic injuries induced by prolonged deep hypothermia circulatory arrest through a peroxisome proliferator-activated receptor gamma coactivator 1-alpha pathway.