Publications by authors named "Neel R Sodha"

69 Publications

Dialysis and Endocarditis: Proving What We Know, Learning What We Didn't.

Authors:
Neel R Sodha

J Am Coll Cardiol 2021 Apr;77(13):1641-1643

Division of Cardiothoracic Surgery, Alpert Medical School, Brown University Rhode Island Hospital, Providence, Rhode Island, USA. Electronic address:

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http://dx.doi.org/10.1016/j.jacc.2021.02.034DOI Listing
April 2021

Commentary: Of Mice to Men: Mitigating Spinal Cord Injury During Complex Thoracic Aortic Surgery.

Semin Thorac Cardiovasc Surg 2021 Mar 1. Epub 2021 Mar 1.

Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, Rhode Island. Electronic address:

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http://dx.doi.org/10.1053/j.semtcvs.2021.02.009DOI Listing
March 2021

Commentary: Distension Kills: Venting the Left Ventricle During Venoarterial ECMO Support.

Semin Thorac Cardiovasc Surg 2021 Feb 15. Epub 2021 Feb 15.

Division of Cardiothoracic Surgery, Alpert Medical School, Brown University, Providence, Rhode Island. Electronic address:

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http://dx.doi.org/10.1053/j.semtcvs.2021.01.018DOI Listing
February 2021

Effects of High Fat Versus Normal Diet on Extracellular Vesicle-Induced Angiogenesis in a Swine Model of Chronic Myocardial Ischemia.

J Am Heart Assoc 2021 Feb 9;10(4):e017437. Epub 2021 Feb 9.

Division of Cardiothoracic Surgery Alpert Medical School of Brown University and Rhode Island Hospital Providence RI.

Background Mesenchymal stem cell-derived extracellular vesicles (EVs) promote angiogenesis in the ischemic myocardium. This study examines the difference in vascular density, myocardial perfusion, molecular signaling, and gene expression between normal diet (ND) and high fat diet (HFD) groups at baseline and following intramyocardial injection of EVs. Methods and Results Intact male Yorkshire swine fed either an ND (n=17) or HFD (n=14) underwent placement of an ameroid constrictor on the left circumflex coronary artery. Subsequently, animals received either intramyocardial injection of vehicle-saline as controls; (ND-controls n=7, HFD-controls, n=6) or EVs; (ND-EVs n=10, HFD-EVs n=8) into the ischemic territory. Five weeks later, myocardial function, perfusion, vascular density, cell signaling, and gene expression were examined. EVs improved indices of myocardial contractile function, myocardial perfusion, and arteriogenesis in both dietary cohorts. Interestingly, quantification of alpha smooth muscle actin demonstrated higher basal arteriolar density in HFD swine compared with their ND counterparts; whereas EVs were associated with increased CD31-labeled endothelial cell density only in the ND tissue, which approached significance. Levels of total endothelial nitric oxide synthase, FOXO1 (forkhead box protein O1) , transforming growth factor-β, phosphorylated VEGFR2 (vascular endothelial growth factor receptor 2), and phosphorylated MAPK ERK1/ERK2 (mitogen-activated protein kinase) were higher in ischemic myocardial lysates from ND-controls compared with HFD-controls. Conversely, HFD-control tissue showed increased expression of phosphorylated endothelial nitric oxide synthase, phosphorylated FOXO1, VEGFR2, and MAPK ERK1/ERK2 with respect to ND-controls. Preliminary gene expression studies indicate differential modulation of transcriptional activity by EVs between the 2 dietary cohorts. Conclusions HFD produces a profound metabolic disorder that dysregulates the molecular mechanisms of collateral vessel formation in the ischemic myocardium, which may hinder the therapeutic angiogenic effects of EVs.
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http://dx.doi.org/10.1161/JAHA.120.017437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955347PMC
February 2021

Prevalence of Deep Vein Thrombosis in Patients Supported With Extracorporeal Membrane Oxygenation.

ASAIO J 2021 Jan 11. Epub 2021 Jan 11.

From the Department of Medicine, Division of Pulmonary, Critical Care & Sleep Medicine, Warren Alpert School of Medicine at Brown University, Providence, Rhode Island Department of Surgery, Warren Alpert School of Medicine at Brown University, Providence, Rhode Island Lifespan Hospital System, Providence, Rhode Island Department of Health Services, Policy & Practice, Brown University School of Public Health, Providence, Rhode Island.

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http://dx.doi.org/10.1097/MAT.0000000000001348DOI Listing
January 2021

Machine learning to predict hemorrhage and thrombosis during extracorporeal membrane oxygenation.

Crit Care 2020 12 10;24(1):689. Epub 2020 Dec 10.

Department of Medicine, Warren Alpert Medical School of Brown University, Providence, RI, USA.

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http://dx.doi.org/10.1186/s13054-020-03403-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7727105PMC
December 2020

Commentary: Time and effort…resources and support: Increasing academic productivity during cardiothoracic surgery residency.

Authors:
Neel R Sodha

J Thorac Cardiovasc Surg 2020 Oct 28. Epub 2020 Oct 28.

Division of Cardiothoracic Surgery, Alpert Medical School, Brown University, Providence, RI. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.10.084DOI Listing
October 2020

Intravenous injection of extracellular vesicles to treat chronic myocardial ischemia.

PLoS One 2020 11;15(9):e0238879. Epub 2020 Sep 11.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, RI, United States of America.

Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) appear to be a very exciting treatment option for heart disease. Here, we used a swine model of chronic myocardial ischemia to evaluate the efficacy of a less-invasive method of injection of EVs via a peripheral intravenous route.

Methods: Sixteen Yorkshire swine underwent placement of an ameroid constrictor on the left circumflex (LCx) artery at age 11 weeks to induce chronic myocardial ischemia. Two weeks later, they were divided into two groups: control (CON; n = 8), and intravenous injection of EVs (EVIV; n = 8). At 18 weeks of age, animals underwent final analysis and euthanasia. The chronically ischemic myocardium (LCx territory) was harvested for analysis.

Results: Intravenous injection (IV) of EVs induced several pro-angiogenic markers such as MAPK, JNK but not Akt. Whereas IV injections of EVs decreased VEGFR2 expression and inhibited apoptotic signaling (caspase 3), they increased expression of VEGFR1 that is believed to be anti-angiogenic. Injection of EVs did not result in an increase in vessel density and blood flow when compared to the control group.

Conclusions: Although IV injection of EVs upregulated several pro-angiogenic signaling pathways, it failed to induce changes in vascular density in the chronically ischemic myocardium. Thus, a lack of increase in vascular density at the doses tested failed to elicit a functional response in ischemic myocardium.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238879PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485873PMC
November 2020

Commentary: Trouble in Paradise? Cardiac Surgical Supply and Demand in the Caribbean.

Authors:
Neel R Sodha

Semin Thorac Cardiovasc Surg 2021 Spring;33(1):132-133. Epub 2020 Jun 29.

Alpert Medical School, Brown University, Providence, Rhode Island. Electronic address:

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http://dx.doi.org/10.1053/j.semtcvs.2020.06.032DOI Listing
June 2020

Commentary: Spinal cord ischemia following aortic surgery: Survey says?

J Thorac Cardiovasc Surg 2020 Mar 31. Epub 2020 Mar 31.

Division of Cardiac Surgery, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2020.03.058DOI Listing
March 2020

Metabolic regulation of endothelial SK channels and human coronary microvascular function.

Int J Cardiol 2020 08 12;312:1-9. Epub 2020 Mar 12.

Division of Cardiothoracic Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States of America. Electronic address:

Background: Diabetic (DM) inactivation of small conductance calcium-activated potassium (SK) channels contributes to coronary endothelial dysfunction. However, the mechanisms responsible for this down-regulation of endothelial SK channels are poorly understood. Thus, we hypothesized that the altered metabolic signaling in diabetes regulates endothelial SK channels and human coronary microvascular function.

Methods: Human atrial tissue, coronary arterioles and coronary artery endothelial cells (HCAECs) obtained from DM and non-diabetic (ND) patients (n = 12/group) undergoing cardiac surgery were used to analyze metabolic alterations, endothelial SK channel function, coronary microvascular reactivity and SK gene/protein expression/localization.

Results: The relaxation response of DM coronary arterioles to the selective SK channel activator SKA-31 and calcium ionophore A23187 was significantly decreased compared to that of ND arterioles (p < 0.05). Diabetes increases the level of NADH and the NADH/NAD ratio in human myocardium and HCAECs (p < 0.05). Increase in intracellular NADH (100 μM) in the HCAECs caused a significant decrease in endothelial SK channel currents (p < 0.05), whereas, intracellular application of NAD (500 μM) increased the endothelial SK channel currents (p < 0.05). Mitochondrial reactive oxygen species (mROS) of HCAECs and NADPH oxidase (NOX) and PKC protein expression in the human myocardium and coronary microvasculature were increased respectively (p < 0.05).

Conclusions: Diabetes is associated with metabolic changes in the human myocardium, coronary microvasculature and HCAECs. Endothelial SK channel function is regulated by the metabolite pyridine nucleotides, NADH and NAD, suggesting that metabolic regulation of endothelial SK channels may contribute to coronary endothelial dysfunction in the DM patients with diabetes.
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http://dx.doi.org/10.1016/j.ijcard.2020.03.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388214PMC
August 2020

Lower preoperative hematocrit, longer hospital stay, and neurocognitive decline after cardiac surgery.

Surgery 2020 07 14;168(1):147-154. Epub 2020 Mar 14.

Brown University School of Medicine, Division of Cardiothoracic Surgery, Rhode Island Hospital, Providence, RI. Electronic address:

Background: Cardiopulmonary bypass may be associated with postoperative neurocognitive dysfunction; however, risk factors have not been clearly identified. We hypothesize that lower hematocrit levels are correlated with postoperative neurocognitive dysfunction.

Methods: A total of 30 patients underwent cardiac operations utilizing cardiopulmonary bypass and screening for neurocognitive dysfunction preoperatively and on postoperative day 4. Patients were analyzed according to hematocrit preoperatively, 6 hours postoperatively, and on postoperative day 4, and whether they received intra or postoperative transfusions of packed red blood cells. Neurocognitive data is presented as a difference in Repeatable Battery for the Assessment of Neuropsychological Status standardized score from baseline to postoperative day 4 and analyzed by unpaired two-tailed Spearman test and unpaired Mann-Whitney U test.

Results: There was a significant correlation between patients with lower hematocrit before surgery and a decline in neurocognitive function at postoperative day 4 (P < .05). All patients experienced a decrease in hematocrit during their hospital stay, but the hematocrit 6 hours postoperatively and postoperative day 4 did not impact cognition. Receiving a transfusion was also not associated with neurocognitive dysfunction. Patients with low hematocrit preoperatively had a consistently lower hematocrit throughout their stay. Prolonged total length of stay was also significantly associated with neurocognitive decline.

Conclusion: A lower preoperative hematocrit and prolonged length of hospital stay are correlated with neurocognitive decline after cardiac surgery utilizing cardiopulmonary bypass.
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http://dx.doi.org/10.1016/j.surg.2020.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311300PMC
July 2020

Extracorporeal Life Support in Adults with Acute Respiratory Failure: Current Evidence-Based Practices.

R I Med J (2013) 2019 Dec 2;102(10):39-42. Epub 2019 Dec 2.

Department of Medicine, Warren Alpert Medical School of Brown University; Department of Health Services, Policy & Practice, Brown School of Public Health, Providence, RI.

There has been rapid adoption of extracorporeal life support (ECLS) in adult patients with severe acute respiratory failure. Extracorporeal membrane oxygenation (ECMO) is used to rescue patients with severe hypoxemic and hypercapnic respiratory failure refractory to optimal therapy and extracorporeal carbon dioxide removal (ECCO2R) supports hypercapnic respiratory failure and allows very low tidal volume ventilation to minimize the risk of ventilator-induced lung injury. Currently over 3,000 cases of ECLS (ECMO and ECCO2R) in adults with respiratory failure are reported annually to the Extracorporeal Life Support Organization registry. Advances in the care of patients with acute respiratory distress syndrome, technological innovations in extracorporeal circuitry, and insights from modern clinical trials of ECLS have led to favorable outcomes and a renewed interest in the use of this technology. Significant gaps in knowledge about best practices remain, however. This review will summarize indications for respiratory support in adults, current evidence available from clinical trials and our institution's experience with adult respiratory ECLS.
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December 2019

Right Ventricular Failure Post-Implantation of Left Ventricular Assist Device: Prevalence, Pathophysiology, and Predictors.

ASAIO J 2020 06;66(6):610-619

Division of Cardiology, Department of Medicine, Lifespan Cardiovascular Institute and The Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Despite advances in left ventricular assist device (LVAD) technology, right ventricular failure (RVF) continues to be a complication after implantation. Most patients undergoing LVAD implantation have underlying right ventricular (RV) dysfunction (either as a result of prolonged LV failure or systemic disorders) that becomes decompensated post-implantation. Additional insults include intra-operative factors or a sudden increase in preload in the setting of increased cardiac output. The current literature estimates post-LVAD RVF from 3.9% to 53% using a diverse set of definitions. A few of the risk factors that have been identified include markers of cardiogenic shock (e.g., dependence on inotropes and Interagency Registry for Mechanically Assisted Circulatory Support profiles) as well as evidence of cardiorenal or cardiohepatic syndromes. Several studies have devised multivariable risk scores; however, their performance has been limited. A new functional assessment of RVF and a novel hepatic marker that describe cholestatic properties of congestive hepatopathy may provide additional predictive value. Furthermore, future studies can help better understand the relationship between pulmonary hypertension and post-LVAD RVF. To achieve our ultimate goal-to prevent and effectively manage RVF post-LVAD-we must start with a better understanding of the risk factors and pathophysiology. Future research on the different etiologies of RVF-ranging from acute post-surgical complication to late-onset RV cardiomyopathy-will help standardize definitions and tailor therapies appropriately.
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http://dx.doi.org/10.1097/MAT.0000000000001088DOI Listing
June 2020

Extracellular Vesicles Promote Arteriogenesis in Chronically Ischemic Myocardium in the Setting of Metabolic Syndrome.

J Am Heart Assoc 2019 08 27;8(15):e012617. Epub 2019 Jul 27.

Division of Cardiothoracic Surgery Department of Surgery Cardiovascular Research Center Rhode Island Hospital Warren Alpert Medical School of Brown University Providence RI.

Background Ischemic heart disease continues to be a leading cause of mortality in patients. Extracellular vesicles (EVs) provide a potential for treatment that may induce collateral vessel growth to increase myocardial perfusion. Methods and Results Nineteen male Yorkshire pigs were given a high-fat diet for 4 weeks, then underwent placement of an ameroid constrictor on the left circumflex artery to induce chronic myocardial ischemia. Two weeks later, the pigs received either intramyocardial vehicle (n=6), EVs (high-fat diet with myocardial EV injection [HVM]; n=8), or HVM and calpain inhibition (n=5). Five weeks later, myocardial function, perfusion, coronary vascular density, and cell signaling were examined. Perfusion in the collateral-dependent myocardium was increased during rapid ventricular pacing in the HVM group in both nonischemic (P=0.04) and ischemic areas of the ventricle (P=0.05). Cardiac output and stroke volume were significantly improved in the HVM group compared with the control group during ventricular pacing (P=0.006). Increased arteriolar density was seen in the HVM group in both nonischemic and ischemic myocardium (P=0.003 for both). However, no significant changes in the capillary density were observed between the control, HVM, and HVM and calpain inhibition groups (P=0.07). The group that received EVs with oral calpain inhibition had neither increased vessel density (P>0.99) nor improvement in blood flow or cardiac function (P=0.48) when compared with the control group. Conclusions These findings suggest that EVs promote angiogenesis in areas of chronic myocardial ischemia and improve cardiac function under conditions of diet-induced metabolic syndrome.
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http://dx.doi.org/10.1161/JAHA.119.012617DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761642PMC
August 2019

Commentary: Hybrid thoracoabdominal aortic aneurysm repair: One step closer with the SPIDER graft.

J Thorac Cardiovasc Surg 2019 09 12;158(3):704-705. Epub 2018 Dec 12.

Division of Cardiothoracic Surgery, Department of Surgery, Alpert Medical School, Brown University, Providence, RI. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2018.11.112DOI Listing
September 2019

Impact of Packed Red Blood Cell and Platelet Transfusions in Patients Undergoing Dissection Repair.

J Surg Res 2018 12 18;232:338-345. Epub 2018 Jul 18.

Division of Cardiothoracic Surgery, Rhode Island Hospital, The Warren Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address:

Background: Transfusion of blood products commonly occur in patients undergoing repair of acute type A aortic dissection (AADA).

Materials And Methods: The medical records of 102 AADA patients were retrospectively reviewed and stratified into cohorts by packed red blood cell (PRBC) and platelet units received: PRBC ≤2 units (n = 68) versus PRBC >2 units (n = 34); platelets ≤1 unit (n = 74) versus platelets >1 unit (n = 28). Continuous and categorical variables were assessed by analysis of variance testing and chi-square or Fisher's testing as appropriate. Multivariate logistic regression was applied to derive P values for post-transfusion complications. Kaplan-Meier survival analyses were used to compare the hospital length of stay (LOS) and survival rate at 1 mo and 1 y.

Results: Patients receiving >2 units of PRBC had a median LOS of 14 d versus 9 d for those receiving ≤2 units (P < 0.002). Transfusion of >2 units of PRBC was a risk factor for postoperative infection (odds ratio [OR] = 5.4, 95% confidence interval [CI]: 1.5-19.0, P = 0.009). Survival at 1 mo was 91% versus 94% (P = 0.783) and 1 y survival was 82% versus 93% (P = 0.269) between the two groups. Patients receiving >1 unit of platelets had a median LOS of 15 d versus 10 d for those receiving ≤1 unit (P = 0.005). Transfusion of >1 unit of platelets was a risk factor for postoperative atrial fibrillation and acute kidney injury (OR = 2.9, 95% CI: 1.1-7.6, P = 0.031; OR = 3.3, 95% CI: 1.2-9.4, P = 0.025, respectively). Survival at 1 mo was 93% versus 93% (P = 0.872) and 1 y survival was 81% versus 92% (P = 0.582) between the two groups.

Conclusions: Transfusion of PRBC and platelets above a threshold increases the incidence of postoperative complications and hospital LOS among patients undergoing repair of AADA.
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http://dx.doi.org/10.1016/j.jss.2018.06.048DOI Listing
December 2018

Extracellular Vesicle Injection Improves Myocardial Function and Increases Angiogenesis in a Swine Model of Chronic Ischemia.

J Am Heart Assoc 2018 06 12;7(12). Epub 2018 Jun 12.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI

Background: Mesenchymal stem cell-derived extracellular vesicles (EVs) are believed to be cardioprotective in myocardial infarct. The objective of this study was to examine the effects of human mesenchymal cell-derived EV injection on cardiac function, myocardial blood flow, and vessel density in the setting of chronic myocardial ischemia.

Methods And Results: Twenty-three Yorkshire swine underwent placement of an ameroid constrictor on their left circumflex artery. Two weeks later, the animals were split into 2 groups: the control group (CON; n=7) and the EV myocardial injection group (MVM; n=10). The MVM group underwent myocardial injection of 50 μg of EVs in 2 mL 0.9% saline into the ischemic myocardium. Five weeks later, the pigs underwent a harvest procedure, and the left ventricular myocardium was analyzed. Absolute blood flow and the ischemic/nonischemic myocardial perfusion ratio were increased in the ischemic myocardium in the MVM group compared with the CON group. Pigs in the MVM group had increased capillary and arteriolar density in the ischemic myocardial tissue compared with CON pigs. There was an increase in expression of the phospho-mitogen-activated protein kinase/mitogen-activated protein kinase ratio, the phospho-endothelial nitric oxide synthase/endothelial nitric oxide synthase ratio, and total protein kinase B in the MVM group compared with CON. There was an increase in cardiac output and stroke volume in the MVM group compared with CON.

Conclusions: In the setting of chronic myocardial ischemia, myocardial injection of human mesenchymal cell-derived EVs increases blood flow to ischemic myocardial tissue by induction of capillary and arteriolar growth via activation of the protein kinase B/endothelial nitric oxide synthase and mitogen-activated protein kinase signaling pathways resulting in increased cardiac output and stroke volume.
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http://dx.doi.org/10.1161/JAHA.117.008344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6220556PMC
June 2018

Glycogen synthase kinase 3β inhibition reduces mitochondrial oxidative stress in chronic myocardial ischemia.

J Thorac Cardiovasc Surg 2018 06 2;155(6):2492-2503. Epub 2018 Feb 2.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address:

Objectives: Glycogen synthase kinase 3β (GSK-3β) inhibition has been reported to increase microvascular density and improve myocardial blood flow in a porcine model of chronic myocardial ischemia and metabolic syndrome. Inhibition of GSK-3β can also be cardioprotective by modulating fibrosis signaling and mitochondrial-induced apoptosis. We hypothesized GSK-3β inhibition would have a beneficial effect on myocardial fibrosis and oxidative stress in a porcine model of chronic myocardial ischemia and metabolic syndrome.

Methods: Pigs were fed a high fat diet for 4 weeks followed by placement of an ameroid constrictor to the left circumflex coronary artery. Three weeks later animals received either no drug or a GSK-3β inhibitor. The diets and placebo/GSK-3β inhibition were continued for an additional 5 weeks, the pigs were then euthanized, and the myocardial tissue was harvested. Collagen expression was analyzed via Picrosirius staining. Oxidative stress was analyzed via Oxyblot analysis. Protein expression was analyzed via Western blot.

Results: GSK-3β inhibition was associated with decreased collagen expression and oxidative stress in the ischemic and nonischemic myocardial tissue compared with control. There was a decrease in profibrotic proteins transforming growth factor-β, p-SMAD2/3, and matrix metalloproteinase-9, and in proapoptotic and oxidative stress proteins, apoptosis inducing factor, the cleaved caspase 3/caspase 3 protein ratio and phosphorylated myeloid cell leukemia sequence-1 in the GSK-3β inhibited group compared with the control.

Conclusions: In the setting of metabolic syndrome and chronic myocardial ischemia, inhibition of GSK-3β decreases collagen formation and oxidative stress in myocardial tissue. GSK-3β inhibition might be having this beneficial effect by downregulating transforming growth factor-β/SMAD2/3 signaling and decreasing mitochondrial induced cellular stress.
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http://dx.doi.org/10.1016/j.jtcvs.2017.12.127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5960424PMC
June 2018

Predictors of patient radiation exposure during transcatheter aortic valve replacement.

Catheter Cardiovasc Interv 2018 10 27;92(4):768-774. Epub 2017 Dec 27.

Division of Cardiology, Warren Alpert Medical School of Brown University, Providence, Rhode Island.

Background: Transcatheter aortic valve replacement (TAVR) exposes patients to radiation.

Objectives: We sought to identify factors associated with higher radiation exposure and to quantify their relative influence, which may inform reduction of this hazard.

Methods: All TAVR procedures at Rhode Island Hospital between March 20, 2012 and February 12, 2017 were included. Procedures were performed by two co-primary operators using a Siemens Artis Zeego system. Radiation metrics were generated by the imaging system. The primary metric was dose-area product (DAP, Gy*cm ), and secondary metrics were reference point air kerma (mGy) and fluoroscopy time (minutes). Data collected for the STS/ACC TVT Registry were utilized to develop a multivariable linear regression model predicting DAP.

Results: In 294 TAVRs, median DAP was 169 Gy*cm [interquartile range (IQR) 106-238]. The r values for the full 27-variable DAP model and reduced eight-variable model were 0.457 and 0.420, respectively. Valve area, aortic insufficiency, and procedure year (suggesting absence of a learning curve) were non-significant predictors in the full model, while increasing weight, cutdown transfemoral access, higher pre-procedure creatinine and hemoglobin, and vascular complications predicted higher DAP in both models. Results were unchanged when DAP was log-transformed. Secondary models for air kerma and fluoroscopy time revealed similar predictors.

Conclusion: Factors associated with increased procedural complexity and duration as well as radiation attenuation and scatter predict increased patient radiation exposure during TAVR. Modification of procedural technique, especially using percutaneous femoral vascular access, may facilitate reduction in exposure.
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http://dx.doi.org/10.1002/ccd.27452DOI Listing
October 2018

Managing the atheromatous aorta: Solutions still in evolution.

Authors:
Neel R Sodha

J Thorac Cardiovasc Surg 2018 02 20;155(2):517. Epub 2017 Sep 20.

Division of Cardiothoracic Surgery, Alpert Medical School Brown University, Providence, RI. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2017.09.057DOI Listing
February 2018

Novel molecular targets for coronary angiogenesis and ischemic heart disease.

Coron Artery Dis 2017 Nov;28(7):605-613

Department of Cardiothoracic Surgery, Research Division, Institution of Warren Alpert Medical School Brown University, Providence, Rhode Island, USA.

Coronary artery disease (CAD) is the number one cause of death among men and women in the USA. Genetic predisposition and environmental factors lead to the development of atherosclerotic plaques in the vessel walls of the coronary arteries, resulting in decreased myocardial perfusion. Treatment includes a combination of revascularization procedures and medical therapy. Because of the high surgical risk of many of the patients undergoing revascularization procedures, medical therapies to reduce ischemic disease are an area of active research. Small molecule, cytokine, endothelial progenitor cell, stem cell, gene, and mechanical therapies show promise in increasing the collateral growth of blood vessels, thereby reducing myocardial ischemia.
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http://dx.doi.org/10.1097/MCA.0000000000000516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5624824PMC
November 2017

Management strategies and possible risk factors for ventricular septal defects after transcatheter aortic valve replacement: Case series from a single center and review of literature.

Cardiovasc Revasc Med 2017 Sep 8;18(6):462-470. Epub 2017 Apr 8.

Division of Cardiothoracic Surgery, Department of Surgery, Lifespan Hospitals, Warren Alpert School of Medicine, Brown University, Providence, RI. Electronic address:

Development of membranous ventricular septal defects (VSD) is a rare complication of transcatheter aortic valve replacements (TAVR), and is recognized using intraoperative and postoperative imaging. We present two cases of this rare but serious complication; one was successfully managed conservatively and the other with valve-in-valve therapy. Management strategies for post-TAVR VSDs varies, but should be individualized to the clinical scenario. We performed a literature search and sought to identify various risk factors which may predispose patients to the development of VSD after TAVR.
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http://dx.doi.org/10.1016/j.carrev.2017.04.003DOI Listing
September 2017

Complex homograft aortic reconstruction: New recipes from old ingredients.

Authors:
Neel R Sodha

J Thorac Cardiovasc Surg 2017 05 3;153(5):e77-e79. Epub 2017 Feb 3.

Department of Surgery, Lifespan Thoracic Aortic Center, Providence, RI; Division of Cardiac Surgery, Alpert Medical School, Brown University, Providence, RI. Electronic address:

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http://dx.doi.org/10.1016/j.jtcvs.2017.01.027DOI Listing
May 2017

Calpain inhibition modulates glycogen synthase kinase 3β pathways in ischemic myocardium: A proteomic and mechanistic analysis.

J Thorac Cardiovasc Surg 2017 02 16;153(2):342-357. Epub 2016 Nov 16.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI. Electronic address:

Background: Calpain inhibition has an enhancing effect on myocardial perfusion and improves myocardial density by inhibiting glycogen synthase kinase 3β (GSK-3β) and up-regulating downstream signaling pathways, including the insulin/PI3K and WNT/β-catenin pathways, in a pig model of chronic myocardial ischemia in the setting of metabolic syndrome.

Methods: Pigs were fed a high-fat diet for 4 weeks, then underwent placement of an ameroid constrictor to the left circumflex artery. Three weeks later, the animals received no drug (high-cholesterol controls [HCC]), a high-dose calpain inhibitor (HCI), a low-dose calpain inhibitor (LCI), or a GSK-3β inhibitor (GSK-3βI). The diets and drug regimens were continued for 5 weeks and the myocardial tissue was harvested.

Results: Calpain and GSK-3β inhibition caused an increase in myocardial perfusion ratios at rest and during pacing compared with controls. Pigs in the LCI and HCI groups had increased vessel density in the ischemic myocardium, and pigs in the GSK-3βI group had increased vessel density in the ischemic and nonischemic myocardium compared with the HCC group. Calpain inhibition modulates proteins involved in the insulin/PI3K and WNT/β-catenin pathways. Quantitative proteomics revealed that calpain and GSK-3β inhibition significantly modulated the expression of proteins enriched in cytoskeletal regulation, metabolism, respiration, and calcium-binding pathways.

Conclusions: In the setting of metabolic syndrome, calpain or GSK-3β inhibition increases vessel density in both ischemic and nonischemic myocardial tissue. Calpain inhibition may exert these effects through the inhibition of GSK-3β and up-regulation of downstream signaling pathways, including the insulin/PI3K and WNT/β-catenin pathways.
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http://dx.doi.org/10.1016/j.jtcvs.2016.09.087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5250534PMC
February 2017

Glycogen Synthase Kinase 3β Inhibition Improves Myocardial Angiogenesis and Perfusion in a Swine Model of Metabolic Syndrome.

J Am Heart Assoc 2016 07 12;5(7). Epub 2016 Jul 12.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI

Background: Inhibition of glycogen synthase kinase 3β (GSK-3β) has been reported to be cardioprotective during stressful conditions.

Methods And Results: Pigs were fed a high-fat diet for 4 weeks to develop metabolic syndrome, then underwent placement of an ameroid constrictor to their left circumflex artery to induce chronic myocardial ischemia. Two weeks later, animals received either: no drug (high cholesterol control group [HCC]) or a GSK-3β inhibitor (GSK-3β inhibited group [GSK-3βI]), which were continued for 5 weeks, followed by myocardial tissue harvest. Coronary blood flow and vessel density were significantly increased in the GSK-3βI group compared to the HCC group. Expression levels of the following proteins were greater in the GSK-3βI group compared to the HCC group: vascular endothelial growth factor receptor 1 , vascular endothelial cadherin, γ-catenin, β-catenin, protein kinase B, phosphorylated forkhead box O1, and superoxide dismutase 2.

Conclusions: In the setting of metabolic syndrome, inhibition of GSK-3β increases blood flow and vessel density in chronically ischemic myocardium. We identified several angiogenic, cell survival, and differentiation pathways that include β-catenin signaling and AKT/FOXO1, through which GSK-3β appears to improve vessel density and blood flow. These results may provide a potential mechanism for medical therapy of patients suffering from coronary artery disease and metabolic syndrome.
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http://dx.doi.org/10.1161/JAHA.116.003694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015402PMC
July 2016

Reversal of Dabigatran with Idarucizumab.

Expert Rev Cardiovasc Ther 2016 Aug 30;14(8):889-93. Epub 2016 Jun 30.

a Division of Cardiac Surgery, Alpert Medical School , Brown University , Providence , RI , USA.

Introduction: The use of novel oral anticoagulants such as dabigatran has been increasing over the last five years. Indicated for use in the prevention of thromboembolic complications from non-valvular atrial fibrillation and for the treatment and prevention of venous thromboembolic disease, dabigatran is increasingly encountered clinically. Lack of an efficacious reversal agent has been a challenge for increased clinical 10 adoption, and for management of patients with bleeding complications while taking dabigatran, or those requiring urgent procedures while taking dabigatran. Idarucizumab, a monoclonal antibody fragment, has recently been approved for use to reverse anticoagulation with dabigatran in patients with serious bleeding.

Areas Covered: Herein we discuss the development and early clinical data evaluating the use of idarucizumab for dabigatran reversal. Expert commentary: Idarucizumab has been shown to be an efficacious reversal agent for patients receiving dabigatran. The drug provides a novel and clinically useful agent for patients with significant bleeding while receiving dabigatran, or those needing urgent invasive procedures.
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http://dx.doi.org/10.1080/14779072.2016.1203253DOI Listing
August 2016

New continuous-flow total artificial heart and vascular permeability.

J Surg Res 2015 Dec 18;199(2):296-305. Epub 2015 Jun 18.

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, Rhode Island. Electronic address:

Background: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability.

Methods: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry.

Results: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance.

Conclusions: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.
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http://dx.doi.org/10.1016/j.jss.2015.06.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636951PMC
December 2015

Differential impairment of adherens-junction expression/phosphorylation after cardioplegia in diabetic versus non-diabetic patients.

Eur J Cardiothorac Surg 2016 Mar 11;49(3):937-43. Epub 2015 Jun 11.

Division of Cardiothoracic Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, USA

Objectives: Previous animal studies have demonstrated that endothelial adherens-junction molecules are significantly altered in animal myocardium and microvasculature after cardioplegia and cardiopulmonary bypass (CP/CPB). We investigated the effects of diabetes on expression/phosphorylation/localization of vascular endothelial (VE)-cadherin, β- and γ-catenin in human atrial myocardium and coronary vasculature in the setting of CP/CPB.

Methods: Right atrial tissue was harvested pre- and post-CP/CPB from non-diabetic (ND) [haemoglobin A1c (HbA1c): 5.4 ± 0.15], controlled (CDM) (HbA1c: 6.3 ± 0.14) and uncontrolled diabetic (UDM) (HbA1c: 9.9 ± 0.72) patients (n = 10/group). Expression/phosphorylation/localization of VE-cadherin, β- and γ-catenin were assessed by immunoblotting, immunoprecipitation and immunohistochemistry. In vitro atrial microvascular reactivity was assessed by videomicroscopy in response to the endothelium-dependent vasodilator adenosine 5'-diphosphate (ADP).

Results: There were no significant differences in VE-cadherin protein expression between pre- and post-CP/CPB among groups. There were significant decreases in VE-cadherin densities in vessels of the UDM group versus the ND group at baseline or post-CP/CPB, respectively (P < 0.05). The level of basal phosphorylated VE-cadherin tends to be higher in the UDM compared with the ND group (P < 0.05). CP/CPB induced more phosphorylation of VE-cadherin in all groups (versus pre-CP/CPB; P < 0.05, respectively) and this effect was more pronounced in the UDM group (P < 0.05 versus ND or CDM). The protein levels of both catenins (β and γ) were lower in post-CP/CPB in UDM than ND patients (P < 0.05). There were significant decreases in vasodilatory response to endothelial-dependent vasodilator ADP after CP/CPB (P < 0.05). This alteration was more pronounced in UDM patients (P < 0.05).

Conclusions: These data suggest that poorly controlled diabetes down-regulates endothelial adherens-junction protein activation/expression/localization in the setting of CP/CPB. The increased tyrosine phosphorylation and deterioration of VE-cadherin indicate the damage of the cell-cell endothelial junctions in the diabetic vessels undergoing CP/CPB and cardiac surgery. These alterations may lead to increase in vascular permeability and endothelial dysfunction and affect outcomes in diabetic patients after cardiac surgery.
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http://dx.doi.org/10.1093/ejcts/ezv202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744457PMC
March 2016

The effect of statins on perioperative inflammation in cardiac and thoracic surgery.

J Thorac Cardiovasc Surg 2015 Jun 11;149(6):1495-501. Epub 2015 Feb 11.

Division of Cardiothoracic Surgery, Alpert Medical School of Brown University, Providence, RI. Electronic address:

Statins are being used with increasing frequency for indications beyond lipid-lowering therapy. In the perioperative setting, the use of statins as anti-inflammatory agents has been an area of growing interest. Despite the early clinical adoption, the data are controversial. Herein we review the available clinical trials examining the effects of statin therapy on perioperative markers of inflammation in cardiac and thoracic surgery.
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http://dx.doi.org/10.1016/j.jtcvs.2015.02.005DOI Listing
June 2015