Myeloid Progenitor Inhibitory Factor-1 (CCL23) Inhibits Lung Leukocyte Recruitment in a Primate Cardiopulmonary Bypass-Induced Pulmonary Ischaemia Model.

BACKGROUND: Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine with potent suppressor effects on myeloid progenitor cells, in vivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown. METHODS: Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes kinetics were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5) intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines, CD11b, and L-selectin were considered leukocytic activation markers. RESULTS: The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7-95.5±4.1 hours [control]; MO, 91.6±5.0-62.0±3.0 hours [control]) and reduced their alveolar appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected. CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed. CONCLUSIONS: CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their circulatory release and lung recruitment. CCL23 has inhibitory effects specifically on the CPB-induced BM response and could hold value for preventing CPB-induced lung injury.

Successful surgical resection plus surgical cryoablation for the treatment of a large left ventricular fibroma.

Residual tumor mass after large cardiac fibroma resection carries long-term risk, but cryoablation is useful during surgery to remove such tissue. Here, we present a case of a large cardiac fibroma of the posterior wall of the left ventricle, discovered during long-term, episodic ventricular tachycardia. Resection with cryoablation completely removed the tumor, eliminating postoperative, distant ventricular arrhythmias.

Arterial switch operation with coronary button extension and neo-pulmonary trunk realignment for a rare coronary pattern.

Coronary anatomy is key for arterial switch operations as reimplantation for coronary artery patterns originating from the same sinus is often challenging. We experienced an extremely rare coronary artery anatomy case (Leiden convention: 1 R, 1LCx) and successfully performed an arterial switch operation with coronary button extension and neo-pulmonary trunk realignment maneuver.

Pediatric cardiac tamponade caused by metallic wire penetration into the heart: A case report and literature review.

Thin, metallic wires can easily penetrate the gastrointestinal system if ingested and cause serious cardiac issues in children. We report a pediatric case of such an object that caused cardiac tamponade after lodging in the left ventricle. The wire was extracted without cardiopulmonary bypass and a full recovery was made. Cardiac issues after ingestion of foreign objects are rare but immediate surgery is required for resolution.

Architecture matters: Tissue preservation strategies for tetralogy of Fallot repair.

BACKGROUND: Great variability exists in repair strategies for the tetralogy of Fallot. While transannular patching, as introduced by Kirklin, was a breakthrough for primary repair, pulmonary regurgitation and a need for reoperation have led to the development of methods that preserve the natural morphology of the right ventricular outflow tract. METHODS: State-of-the-art details of tetralogy of Fallot repair are explained from the standpoint of architectural preservation, especially with regard to sparing native tissue such as the annulus, valve, or infundibulum. Particular attention is given to the latest technical details of each approach, benefits and disadvantages, and any long-term data available. RESULTS: The choice of procedure is complex and unique to each case as transannular patching alone may carry long-term pulmonary risks. Modifications that spare the annulus, valves, or infundibulum may thus be essential as preservation of natural morphology has resulted in excellent mid-term results. CONCLUSIONS: The complexity of tetralogy of Fallot repair demands constant attention to clinical presentation and vigilance against long-term sequelae. Techniques will continue to improve over time as long-term data guides the refinement of these innovative surgical methods.

The Validity and Reliability of the Japanese Version of the Cornell Assessment of Pediatric Delirium.

OBJECTIVES: To examine validity and reliability of the Japanese version of the Cornell Assessment of Pediatric Delirium. DESIGN: Prospective double-blinded observational cohort study. SETTING: Eight-bed mixed PICU (post-surgical and internal medicine) from May 2017 to June 2018. PATIENTS: All children between the ages of 0-13 years who were admitted to the PICU for at least 24 hours were eligible for inclusion, as long as the child was arousable to verbal stimulation. INTERVENTIONS: Two nurses simultaneously and independently assessed each patient for pediatric delirium with the Japanese version of the Cornell Assessment of Pediatric Delirium; this was compared to the gold standard of psychiatric diagnosis based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition standards. MEASUREMENTS AND MAIN RESULTS: Forty-one children were enrolled and 92 assessments (ranging from one to four per subject) were completed. Congenital heart disease patients accounted for 73 enrollees (79%). Forty-three percent of observations were performed in children on invasive mechanical ventilation. Pediatric delirium prevalence (as determined by psychiatric diagnosis) was 53%. The Japanese version of the Cornell Assessment of Pediatric Delirium demonstrated an optimal scoring cutpoint of 9. Overall, area under the curve was 92%, sensitivity 90% (95% CI, 79-97%), specificity 88% (95% CI, 75-96%), positive predictive value of 90% (95% CI, 79-97%), negative predictive value of 91% (95% CI, 80-97%), and a Cohen's κ of 0.89 (95% CI, 0.8-0.98). In children on invasive mechanical ventilation, the Japanese version of the Cornell Assessment of Pediatric Delirium maintained an area under the curve 87%, sensitivity 97%, and specificity 64%. CONCLUSIONS: The Japanese version of the Cornell Assessment of Pediatric Delirium is a valid and reliable tool for use in Japanese PICUs. This will allow for detection of delirium in real-time and may lead to better identification of the population and risk factors for appropriate management and therapeutic and preventative interventions.

Rolipram plus Sivelestat inhibits bone marrow-derived leukocytic lung recruitment after cardiopulmonary bypass in a primate model.

Cardiopulmonary bypass (CPB) recovery is complicated by lung inflammation from bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO). Although Sivelestat reduces inflammatory mediators and Rolipram inhibits PMN and MO activation, any kinetic effects to improve CPB recovery in vivo are unknown. We hypothesized that intraoperative co-administration of these compounds would reduce CPB-induced lung inflammation through downregulation of PMN and MO recruitment. A 2-h CPB was surgically established in cynomolgus monkeys (n = 13), and BM leukocyte release and lung recruitment were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Either Sivelestat, Sivelestat plus Rolipram, or saline (control) was administered intraoperatively and both peripheral and perfusion sampling courses revealed BrdU-labeled cells representative of activated leukocyte infiltration. Levels of cytokines CD11b and CD18 were leukocytic activation markers. Sivelestat plus Rolipram attenuated increases in CPB-associated circulating band cells, prolonged BM-transit time (PMN: 121.0 ± 3.7 to 96.2 ± 4.3 h [control], p = 0.012; MO: 84.4 ± 4.1 to 61.4 ± 3.0 h [control], p = 0.003), and reduced their alveolar appearance. CD11b-mediated PMN and MO changes during CPB and the post-surgical increases of Interleukin (IL)-6 and IL-8 in the bronchoalveolar lavage fluid were suppressed. Sivelestat alone increased PMN transit time to 115.8 ± 6.6 h, but monocytes were unaffected. Therefore, Rolipram has additive inhibitory effects with Sivelestat on the CPB-induced activation and release of BM-derived PMNs and MO and their recruitment to the lungs. Co-administration of these compounds could, therefore, hold value for preventing CPB-induced lung injury.

Successful surgical management for aneurysms of single coronary artery with a fistulous connection to the right ventricle.

While a coronary artery fistula with aneurysmal formation is rare, a fistula/aneurysm combination occurring in single coronary artery is even rarer. Here, we report the successful surgical correction of a right ventricular fistula with a large aneurysm of 30 mm and a daughter aneurysm within a case of single coronary artery.

[Aortic Valve Replacement Concomitant with Right and Left Ventricular Outflow Tract Repair Eight Years after Arterial Switch Operation for Double Outlet Right Ventricle;Report of a Case].

We report a case of successful aortic valve replacement and relief of right and left ventricular outflow tract obstruction 8 years after an arterial switch operation for double outlet right ventricle. Since the surgical access to the ascending aorta was limited because of the anatomical feature and the adhesion after the arterial switch operation, arterial infusion site for cardiopulmonary bypass was secured at the right common carotid artery ahead of the sternal re-entry. After cardiopulmonary bypass was established, the right pulmonary artery was divided and then dissection of the ascending aorta was completed to secure the space for aortic valve replacement. A discrete membrane of the left ventricular outflow and muscle bands of the right ventricular outflow were completely resected. The right pulmonary artery was reconstructed by interpose of a prosthetic graft. Our experience would provide a technical option how to handle complex late complications after the arterial switch operation.

Left Ventricular Perforation during Catheter Ablation in a Patient with Idiopathic Thrombocytopenic Purpura.

Preoperative gamma-globulin therapy was recently performed to prevent bleeding complications in a patient with concomitant idiopathic thrombocytopenic purpura undergoing cardiac surgery. Here we report the case of a 75-year-old male patient with idiopathic thrombocytopenic purpura, chronic aortic dissection, and funnel chest in whom a left ventricular perforation sustained during catheter ablation was repaired during emergent surgery. Despite preoperative gamma-globulin therapy not being performed, bleeding complications were prevented because platelets were preserved by avoidance of cardiopulmonary bypass use. Although the funnel chest made it difficult to secure the operative field, the deep pericardial sutures were effective in repairing the perforation without cardiopulmonary bypass.

Early heparin administration attenuates tissue factor-mediated thrombin generation during simulated cardiopulmonary bypass.

BACKGROUND: We tested the hypothesis that heparin administration prior to the emergence of tissue factor (TF) would increase plasma TF pathway inhibitor (TFPI) and attenuate TF-mediated thrombin generation during simulated cardiopulmonary bypass (CPB). METHODS: Human blood was recirculated for 120 minutes using an oxygenator and roller pump. Four groups were examined: control group (heparin 3.75 U/mL, in donor blood, n = 7), rTF group (heparin + recombinant TF 1000 pg/mL, in donor blood, n = 7), TFPI boost group (heparin, in preheparinized donor blood, n = 8), and rTF + TFPI boost group (heparin + rTF, in preheparinized blood, n = 7). In the two TFPI boost groups, 50 U/kg of heparin was given to the donors intravenously five minutes before donation to boost plasma TFPI levels. Total plasma TFPI, thrombin-antithrombin complex, and prothrombin fragment F1+2 levels were measured before and during CPB. RESULTS: Preheparinization increased total plasma TFPI levels by a factor of 8.0. Administration of rTF significantly enhanced the generation of F1+2 (p = 0.0002). The heparin-induced TFPI elevation reduced both thrombin-antithrombin complex and F1+2 to control levels in rTF + TFPI boost group (p = 0.0158 for thrombin-antithrombin complex, p < 0.0001 for F1+2 ). F1+2 levels were at all times lower than control levels in TFPI boost group (p < 0.0001). CONCLUSIONS: Heparin-induced TFPI elevation attenuates TF-mediated thrombin generation. Early heparin administration prior to the emergence of plasma TF may represent a novel strategy for controlling thrombin generation by the extrinsic coagulation pathway during CPB.

Effect of cardiopulmonary bypass on coagulation factors II, VII and X in a primate model: an exploratory pilot study.

OBJECTIVES: The use of cardiopulmonary bypass (CPB) in cardiac surgery is a major risk factor for postoperative bleeding. We hypothesized that consumptive coagulopathy and haemodilution influence the coagulation factors; therefore, we aimed to estimate the activity profiles of coagulation factors II, VII and X during CPB circulation. METHODS: A 120-min bypass was surgically established in cynomolgus monkeys (n = 7). Activities of coagulation factors II, VII and X were measured at 6 time points during the experiment (baseline, 0, 30, 60, 120 min of bypass and 60 min after bypass). To assess the influence of consumptive coagulopathy, the values were adjusted for haemodilution using the haematocrit values. Data were expressed as mean (standard deviation). RESULTS: Activities of coagulation factors decreased during the experiment. In particular, the activities for II, VII and X were decreased the most by 44.2% (5.0), 61.4% (4.3) and 49.0% (3.7) at 30 min following CPB initiation (P < 0.001, P < 0.001 and P < 0.001, respectively). Following adjustments for haemodilution, change magnitudes lessened but remained significant for factor VII. The adjusted concentration of factor VII was observed to decrease from the baseline to the initiation of bypass circulation. CONCLUSIONS: In conclusion, coagulation factor II, VII and X concentrations decreased during CPB. Following adjustment for haemodilution, a decrease in concentration was observed with factor VII.

Congenital Tricuspid Valve Calcification Necessitating Neonatal Surgical Intervention.

We report a case of isolated idiopathic congenital tricuspid valve calcification that necessitated urgent neonatal surgical intervention. Hemodynamic analysis revealed circular shunt caused by severe tricuspid regurgitation, pulmonary regurgitation, and a hypoplastic right ventricle. The patient successfully underwent tricuspid valve repair at postnatal day 10. Although intervention for neonatal tricuspid valve is challenging, hemodynamic evaluation and early surgical intervention are necessary in patients with this rare cardiac calcification.

Expanded Polytetrafluoroethylene Patching for Recurrent Pulmonary Venous Obstructions.

Recurrent postoperative pulmonary venous obstruction after total anomalous pulmonary venous connection repair is a challenging complication. Here, we present such a case that required 4 reoperations, focusing on a sutureless method with an expanded polytetrafluoroethylene patch for the fourth reoperation. The use of artificial patch materials to reconstruct the atrial septum and neoatrial roof could be a promising alternative approach of this method to expand its applicability.

Pediatric delirium is associated with increased brain injury marker levels in cardiac surgery patients.

Despite global consensus on the importance of screening pediatric delirium, correlations between pediatric delirium during acute brain injury and adult delirium are unclear. Therefore, we hypothesized that similar pediatric biomarkers reflect acute brain injury as in adult delirium. We observed pediatric cardiac surgery patients from neonatal age to 18 years, who were admitted to our pediatric intensive care unit after cardiovascular operations between October 2019 to June 2020, up to post-operative day 3 (4 days total). We recorded age, sex, risk score (Risk Adjustment in Congenital Heart Surgery [RACHS-1]), midazolam/dexmedetomidine/fentanyl dosage, and pediatric Sequential Organ Failure Assessment (pSOFA). Richmond Agitation-Sedation Scale (RASS), Cornell Assessment of Pediatric Delirium (CAPD), Face, Leg, Activity, Consolability (FLACC) behavioral scale, and Withdrawal Assessment Tool (WAT-1) scales were used and serum sampling for neuron specific enolase (NSE) was conducted. Consciousness status was considered hierarchical (coma > delirium > normal) and associations between conscious status and NSE were conducted by hierarchical Bayesian modeling. We analyzed 134 data points from 40 patients (median age 12 months). In the multi-regression model, NSE was positively associated with coma [posterior odds ratio (OR) = 1.1, 95% credible interval (CrI) 1.01-1.19] while pSOFA [posterior OR = 1.63, 95% CrI 1.17-2.5], midazolam [posterior OR = 1.02, 95% CrI 1.01-1.04], and dexmedetomidine [posterior OR = 9.52, 95% CrI 1.02-108.85] were also associated. We also evaluated consciousness state probability at each NSE concentration and confirmed both that consciousness was hierarchically sorted and CAPD scores were also associated with NSE [posterior OR = 1.32, 95% CrI 1.09-1.58]. "Eye contact" (r = 0.55) was the most correlated component with NSE within the pain, withdrawal syndrome, and PD items. PD within the hierarchy of consciousness (coma, delirium, normal) and CAPD scores are associated with brain injury marker levels. Using pediatric delirium assessment tools for monitoring brain injury, especially eye contact, is a reliable method for observing PD.

Conduction disorders after perimembranous ventricular septal defect closure: continuous versus interrupted suturing techniques.

OBJECTIVES: The aim of this study was to investigate postoperative conduction disorder differences between continuous and interrupted suturing techniques for the closure of perimembranous outlet-type ventricular septal defects (VSDs) in both tetralogy of Fallot (ToF) and isolated VSD cases. METHODS: Patients aged 4 years or younger who underwent VSD closure for ToF (n = 112) or isolated perimembranous outlet-type VSD (n = 73) from April 2010 to December 2018 at 3 centres were reviewed. Patients either received continuous suturing for ToF (C-ToF, n = 58) or isolated VSD (C-VSD, n = 50), or interrupted suturing for ToF (I-ToF, n = 54) or isolated VSD (I-VSD, n = 23). Cohorts did not differ in preoperative characteristics. Postoperative conduction disorder differences upon discharge and postoperative year 1 (POY1) were evaluated by electrocardiography. RESULTS: The C-ToF group showed significantly shorter PQ intervals (124.0 vs 133.5 ms; P = 0.042 upon discharge, 125.3 vs 133.5 ms; P = 0.045 at POY1) and QRS durations (98.0 vs 106.2 ms; P = 0.031 upon discharge, 97.3 vs 102.5 ms; P = 0.040 at POY1) than the I-ToF group. Right bundle branch block incidence was significantly lower in the C-ToF versus I-ToF groups (56.8 vs 75.9; P = 0.045 upon discharge, 56.8 vs 75.9; P = 0.045 at POY1). Heart rates were significantly lower in the C-ToF versus I-ToF groups at POY1 (109.2 vs 119.3 bpm; P < 0.001). No parameters significantly differed between C-VSD and I-VSD groups. Multivariable analyses confirmed the group (C-ToF versus I-ToF) as a significant covariate in postoperative heart rate, PQ interval, QRS duration and right bundle branch block outcomes at POY1 (P = 0.013, 0.027, 0.013 and 0.014, respectively). CONCLUSIONS: A continuous suturing technique for the closure of outlet-type VSD in ToF could reduce the incidence of postoperative right bundle branch block, shorten the PQ interval and lower heart rate. SUBJECT COLLECTION: 110, 138, 139.

Congenital-idiopathic superficial femoral artery aneurysm in a 7-year-old child.

Superficial femoral artery aneurysm in children is distinctly uncommon, and usually results from infection, vasculitis, connective tissue disorder, or trauma. We report a 7-year-old girl who had multiple fusiform aneurysms of the right superficial femoral artery, with no evidence of related disorders. The patient successfully underwent aneurysm resection and femoral artery reconstruction with autogenous saphenous vein. Histologic examination revealed intimal thickening with fibroplasia without severe inflammatory infiltrates or cystic medial necrosis, suggesting a congenital-idiopathic arterial aneurysm. Three years after the procedure, the saphenous vein graft is fully patent and the patient is in good condition.

Single dose GLP-1-Tf ameliorates myocardial ischemia/reperfusion injury.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic, and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life. MATERIALS AND METHODS: We tested the ability of single dose GLP-1-Tf to limit myocardial ischemia (30 min)/reperfusion (180 min) injury in rabbits. Nineteen animals were untreated controls. The pre-ischemic group (n=10) was given 10mg/kg of GLP-1-Tf 12 h before ischemia. Immediately after reperfusion, the post-ischemic group (n=10) received GLP-1-Tf (10 mg/kg) and the Tf group (n=4) received transferrin alone. RESULTS: Infarct size as a percentage of the area at risk was 59.1% ± 1.3%, 45.7% ± 1.9%, 44.1% ± 3.3%, 59.7% ± 2.0% in the control group, pre-ischemic group, post-ischemic group, and Tf group, respectively (P<0.05 for both GLP-1-Tf treatments group versus control). GLP-1-Tf reduced the apoptotic index from 4.67% ± 0.40% in the control group to 3.15% ± 0.46% in the pre-ischemic group and to 2.66% ± 0.40% in the post-ischemic group (P<0.05 for both GLP-1-Tf treatments versus control). The size of the wall motion abnormality and ejection fraction was significantly improved in the post-ischemic group relative to the control group. Serum GLP-1 levels were 239.8 ± 25.7 µg/mL in the post-ischemic group, 27.9 ± 5.8 µg/mL in the pre-ischemic group, and undetectable in the control group. CONCLUSION: GLP-1-Tf limits myocardial reperfusion injury whether given prior to the onset of ischemia or given at reperfusion. GLP-1-Tf may also limit myocardial stunning at high serum levels of the drug.

Sex-related resistance to myocardial ischemia-reperfusion injury is associated with high constitutive ARC expression.

The female sex has been associated with improved myocardial salvage after ischemia and reperfusion (I/R). Estrogen, specifically 17beta-estradiol, has been demonstrated to mediate this phenomenon by limiting cardiomyocyte apoptosis. We sought to quantitatively assess the effect of sex, ovarian hormone loss, and I/R on myocardial Bax, Bcl-2, and apoptosis repressor with caspase recruitment domain (ARC) expression. Male (n = 48), female (n = 26), and oophorectomized female (n = 20) rabbits underwent 30 min of regional ischemia and 3 h of reperfusion. The myocardial area at risk and infarct size were determined using a double-staining technique and planimetry. In situ oligo ligation was used to assess apoptotic cell death. Western blot analysis was used to determine proapoptotic (Bax) and antiapoptotic (Bcl-2 and ARC) protein levels in all three ischemic groups and, additionally, in three nonischemic groups. Infarct size (43.7 +/- 3.2%) and apoptotic cell death (0.51 +/- 0.10%) were significantly attenuated in females compared with males (56.4 +/- 1.6%, P < 0.01, and 4.29 +/- 0.95%, P < 0.01) and oophorectomized females (55.7 +/- 3.4%, P < 0.05, and 4.36 +/- 0.51%, P < 0.01). Females expressed significantly higher baseline ARC levels (3.62 +/- 0.29) compared with males (1.78 +/- 0.18, P < 0.01) and oophorectomized females (1.08 +/- 0.26, P < 0.01). Males expressed a significantly higher baseline Bax-to-Bcl-2 ratio (4.32 +/- 0.99) compared with females (0.65 +/- 0.13, P < 0.01) and oophorectomized females (0.42 +/- 0.10, P < 0.01). I/R significantly reduced Bax-to-Bcl-2 ratios in males. In all other groups, ARC levels and Bax-to-Bcl-2 ratios did not significantly change. These results support the conclusion that in females, endogenous estrogen limits I/R-induced cardiomyocyte apoptosis by producing a baseline antiapoptotic profile, which is associated with estrogen-dependent high constitutive myocardial ARC expression.

Surgical Resection of an Adventitial Cyst of the Right Brachiocephalic Vein.

Adventitial cystic disease is an uncommon vascular anomaly known to occur in peripheral vessels but mediastinal appearances are extremely rare. Herein, we report the case of an adventitial cyst occurring in the right brachiocephalic vein which might have been associated with ovarian hyperstimulation syndrome.