21 results on '"Saeed MY"'
Search Results
2. Biorobotic hybrid heart as a benchtop cardiac mitral valve simulator.
- Author
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Park C, Singh M, Saeed MY, Nguyen CT, and Roche ET
- Abstract
In this work, we developed a high-fidelity beating heart simulator that provides accurate mitral valve pathophysiology. The benchtop platform is based on a biorobotic hybrid heart that combines preserved intracardiac tissue with soft robotic cardiac muscle providing dynamic left ventricular motion and precise anatomical features designed for testing intracardiac devices, particularly for mitral valve repair. The heart model is integrated into a mock circulatory loop, and the active myocardium drives fluid circulation producing physiological hemodynamics without an external pulsatile pump. Using biomimetic soft robotic technology, the heart can replicate both ventricular and septal wall motion, as well as intraventricular pressure-volume relationships. This enables the system to recreate the natural motion and function of the mitral valve, which allows us to demonstrate various surgical and interventional techniques. The biorobotic cardiovascular simulator allows for real-time hemodynamic data collection, direct visualization of the intracardiac procedure, and compatibility with clinical imaging modalities., Competing Interests: Competing interests: ETR serves on the board of directors for Affluent Medical, as well as the board of advisors for Pumpinheart and Helios Cardio. Additionally, ETR provides consulting services for Holistick Medical and is a co-founder of Fada Medical and Spheric Bio. ETR, CP, and CTN hold a patent for “Organosynthetic dynamic heart model” U.S. Patent Application No. 17/193,910. The other authors have declared that they do not have any competing interests.
- Published
- 2024
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3. Mitochondrial transplantation preserves myocardial function and viability in pediatric and neonatal pig hearts donated after circulatory death.
- Author
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Alemany VS, Nomoto R, Saeed MY, Celik A, Regan WL, Matte GS, Recco DP, Emani SM, Del Nido PJ, and McCully JD
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- Humans, Adult, Child, Infant, Newborn, Swine, Animals, Heart, Myocardium, Brain Death, Perfusion, Infarction, Tissue Donors, Heart Transplantation adverse effects
- Abstract
Objective: Mitochondrial transplantation has been shown to preserve myocardial function and viability in adult porcine hearts donated after circulatory death (DCD) . Herein, we investigate the efficacy of mitochondrial transplantation for the preservation of myocardial function and viability in neonatal and pediatric porcine DCD heart donation., Methods: Circulatory death was induced in neonatal and pediatric Yorkshire pigs by cessation of mechanical ventilation. Hearts underwent 20 or 36 minutes of warm ischemia time (WIT), 10 minutes of cold cardioplegic arrest, and then were harvested for ex situ heart perfusion (ESHP). Following 15 minutes of ESHP, hearts received either vehicle (VEH) or vehicle containing isolated autologous mitochondria (MITO). A sham nonischemic group (SHAM) did not undergo WIT, mimicking donation after brain death heart procurement. Hearts underwent 2 hours each of unloaded and loaded ESHP perfusion., Results: Following 4 hours of ESHP perfusion, left ventricle developed pressure, dP/dt max, and fractional shortening were significantly decreased (P < .001) in DCD hearts receiving VEH compared with SHAM hearts. In contrast, DCD hearts receiving MITO exhibited significantly preserved left ventricle developed pressure, dP/dt max, and fractional shortening (P < .001 each vs VEH, not significant vs SHAM). Infarct size was significantly decreased in DCD hearts receiving MITO as compared with VEH (P < .001). Pediatric DCD hearts subjected to extended WIT demonstrated significantly preserved fractional shortening and significantly decreased infarct size with MITO (P < .01 each vs VEH)., Conclusions: Mitochondrial transplantation in neonatal and pediatric pig DCD heart donation significantly enhances the preservation of myocardial function and viability and mitigates against damage secondary to extended WIT., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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4. Robotic right ventricle is a biohybrid platform that simulates right ventricular function in (patho)physiological conditions and intervention.
- Author
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Singh M, Bonnemain J, Ozturk C, Ayers B, Saeed MY, Quevedo-Moreno D, Rowlett M, Park C, Fan Y, Nguyen CT, and Roche ET
- Subjects
- Animals, Hemodynamics physiology, Swine, Robotics, Models, Cardiovascular, Biomechanical Phenomena physiology, Tricuspid Valve surgery, Tricuspid Valve physiopathology, Sus scrofa, Humans, Ventricular Function, Right physiology, Heart Ventricles physiopathology, Ventricular Dysfunction, Right physiopathology, Ventricular Dysfunction, Right therapy
- Abstract
The increasing recognition of the right ventricle (RV) necessitates the development of RV-focused interventions, devices and testbeds. In this study, we developed a soft robotic model of the right heart that accurately mimics RV biomechanics and hemodynamics, including free wall, septal and valve motion. This model uses a biohybrid approach, combining a chemically treated endocardial scaffold with a soft robotic synthetic myocardium. When connected to a circulatory flow loop, the robotic right ventricle (RRV) replicates real-time hemodynamic changes in healthy and pathological conditions, including volume overload, RV systolic failure and pressure overload. The RRV also mimics clinical markers of RV dysfunction and is validated using an in vivo porcine model. Additionally, the RRV recreates chordae tension, simulating papillary muscle motion, and shows the potential for tricuspid valve repair and replacement in vitro. This work aims to provide a platform for developing tools for research and treatment for RV pathophysiology., Competing Interests: Competing interests E.T.R. is a member of the board of directors at Affluent Medical and also serves on the board of advisors for Pumpinheart and Helios Cardio. E.T.R. offers consulting services for Holistick Medical and is a co-founder of Spheric Bio and Fada Medical. E.T.R., along with C.P. and C.T.N., holds a patent for the “Organosynthetic dynamic heart model” under U.S. Patent Application No. 17/193,910. The remaining authors have stated that they have no competing interests.
- Published
- 2023
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5. Soft robotics-enabled large animal model of HFpEF hemodynamics for device testing.
- Author
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Rosalia L, Ozturk C, Wang SX, Quevedo-Moreno D, Saeed MY, Mauskapf A, and Roche ET
- Abstract
Heart failure with preserved ejection fraction (HFpEF) is a major challenge in cardiovascular medicine, accounting for approximately 50% of all cases of heart failure. Due to the lack of effective therapies for this condition, the mortality associated with HFpEF remains higher than that of most cancers. Despite the ongoing efforts, no medical device has yet received FDA approval. This is largely due to the lack of an in vivo model of the HFpEF hemodynamics, resulting in the inability to evaluate device effectiveness in vivo prior to clinical trials. Here, we describe the development of a highly tunable porcine model of HFpEF hemodynamics using implantable soft robotic sleeves, where controlled actuation of a left ventricular and an aortic sleeve can recapitulate changes in ventricular compliance and afterload associated with a broad spectrum of HFpEF hemodynamic phenotypes. We demonstrate the feasibility of the proposed model in preclinical testing by evaluating the hemodynamic response of the model post-implantation of an interatrial shunt device, which was found to be consistent with findings from in silico studies and clinical trials. This work addresses several of the limitations associated with previous models of HFpEF, such as their limited hemodynamic fidelity, elevated costs, lengthy development time, and low throughput. By showcasing exceptional versatility and tunability, the proposed platform has the potential to revolutionize the current approach for HFpEF device development and selection, with the goal of improving the quality of life for the 32 million people affected by HFpEF worldwide.
- Published
- 2023
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6. An implantable soft robotic ventilator augments inspiration in a pig model of respiratory insufficiency.
- Author
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Hu L, Bonnemain J, Saeed MY, Singh M, Quevedo Moreno D, Vasilyev NV, and Roche ET
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- Swine, Animals, Quality of Life, Ventilators, Mechanical, Prostheses and Implants, Robotics, Respiratory Insufficiency therapy
- Abstract
Severe diaphragm dysfunction can lead to respiratory failure and to the need for permanent mechanical ventilation. Yet permanent tethering to a mechanical ventilator through the mouth or via tracheostomy can hinder a patient's speech, swallowing ability and mobility. Here we show, in a porcine model of varied respiratory insufficiency, that a contractile soft robotic actuator implanted above the diaphragm augments its motion during inspiration. Synchronized actuation of the diaphragm-assist implant with the native respiratory effort increased tidal volumes and maintained ventilation flow rates within the normal range. Robotic implants that intervene at the diaphragm rather than at the upper airway and that augment physiological metrics of ventilation may restore respiratory performance without sacrificing quality of life., (© 2022. The Author(s).)
- Published
- 2023
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7. Tricuspid valve repair concomitant with the Norwood operation among babies with hypoplastic left heart syndrome.
- Author
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Wamala I, Friedman KG, Saeed MY, Gauvreau K, Gellis L, Borisuk M, Kaza A, Emani S, Del Nido PJ, and Baird CW
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- Humans, Infant, Prolapse, Retrospective Studies, Treatment Outcome, Tricuspid Valve diagnostic imaging, Tricuspid Valve surgery, Hypoplastic Left Heart Syndrome diagnostic imaging, Hypoplastic Left Heart Syndrome surgery, Norwood Procedures, Tricuspid Valve Insufficiency complications, Tricuspid Valve Insufficiency diagnostic imaging, Tricuspid Valve Insufficiency surgery
- Abstract
Objectives: Among patients with hypoplastic left heart syndrome (HLHS), tricuspid valve regurgitation (TR) portends a poor prognosis. Our goal was to describe the outcomes of tricuspid valve reconstruction (TVR) concomitant with the Norwood operation and using two-dimensional echocardiography and evaluate the structural factors associated with successful functional correction., Methods: We performed a retrospective, single-centre study of patients with HLHS undergoing TVR at the time of the Norwood operation. Structural echocardiographic parameters were compared between patients with successful correction (≤ mild TR) and those with ≥ moderate regurgitation at discharge. Preoperative dimensions of matched HLHS controls with ≤ trivial TR were used as a reference., Results: Of 205 patients with HLHS undergoing the Norwood operation, 18 patients had a concomitant TVR. Ten (56%) patients had an improved TR grade postoperatively, 8 (44%) of whom had ≤ mild TR at discharge. Improvement in TR grade (P = 0.001) and having ≤ mild TR at discharge (P = 0.011) were associated with an improved reintervention and TR-free survival. Patients with successful functional correction had smaller preoperative tricuspid annulus lateral dimensions (P = 0.023), tricuspid valve area (P = 0.007) and right ventricle mid-width (P = 0.064). Preoperatively, the successful TVR cases tended to have had higher anterior leaflet excursion (80 ± 20 vs 55 ± 11, P = 0.010), and a higher proportion of anterior leaflet prolapse (63% vs 10%, P = 0.043) compared to cases where TVR was not successful., Conclusions: Patients with HLHS with significant tricuspid regurgitation undergoing the stage 1 operation were more likely to have successful concomitant tricuspid valve repair if they had less tricuspid annular dilation, less-severe RV enlargement and predominantly anterior leaflet prolapse. Successful tricuspid valve repair was associated with improved mid- and long-term outcomes., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
- Published
- 2022
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8. Mitochondrial remodeling and ischemic protection by G protein-coupled receptor 35 agonists.
- Author
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Wyant GA, Yu W, Doulamis IP, Nomoto RS, Saeed MY, Duignan T, McCully JD, and Kaelin WG Jr
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- Adenosine Triphosphate metabolism, Animals, Humans, Mice, Proteins metabolism, Rabbits, ATPase Inhibitory Protein, Kynurenic Acid metabolism, Kynurenic Acid pharmacology, Kynurenic Acid therapeutic use, Mitochondria, Heart drug effects, Mitochondria, Heart metabolism, Myocardial Ischemia metabolism, Myocardial Ischemia prevention & control, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled metabolism
- Abstract
Kynurenic acid (KynA) is tissue protective in cardiac, cerebral, renal, and retinal ischemia models, but the mechanism is unknown. KynA can bind to multiple receptors, including the aryl hydrocarbon receptor, the a7 nicotinic acetylcholine receptor (a7nAChR), multiple ionotropic glutamate receptors, and the orphan G protein-coupled receptor GPR35. Here, we show that GPR35 activation was necessary and sufficient for ischemic protection by KynA. When bound by KynA, GPR35 activated G
i - and G12/13 -coupled signaling and trafficked to the outer mitochondria membrane, where it bound, apparantly indirectly, to ATP synthase inhibitory factor subunit 1 (ATPIF1). Activated GPR35, in an ATPIF1-dependent and pertussis toxin-sensitive manner, induced ATP synthase dimerization, which prevented ATP loss upon ischemia. These findings provide a rationale for the development of specific GPR35 agonists for the treatment of ischemic diseases.- Published
- 2022
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9. Major Aortopulmonary Collateral Arteries Requiring Percutaneous Intervention Following the Arterial Switch Operation: A Case Series and Systematic Review.
- Author
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Doulamis IP, Marathe SP, Oh NA, Saeed MY, Muter A, Del Nido PJ, and Nathan M
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- Arteries, Child, Humans, Infant, Newborn, Retrospective Studies, Treatment Outcome, Arterial Switch Operation, Transposition of Great Vessels surgery
- Abstract
Background: Dextro transposition of the great arteries (d-TGA) is the most common critical congenital cardiac defect surgically treated in the neonatal period by arterial switch operation (ASO). Major aortopulmonary collaterals (MAPCAs) can be present in this population and may complicate the early postoperative period. Our aim was to review our institutional data and systematically review the available literature to provide further insight on the clinical significance of MAPCAs during the early postoperative course after ASO. Methods: This is a retrospective study of patients with simple d-TGA who underwent ASO between March 1998 and September 2020 at Boston Children's Hospital. The MEDLINE, Embase, and Cochrane databases were searched from inception to June 2020. Results: Of the 671 d-TGA patients who underwent ASO at our center, 13 (1.9%) were diagnosed with MAPCAs. Five were diagnosed before ASO, while eight were diagnosed after ASO. Of these, two patients required catheterization for MAPCAs coiling during the same hospitalization on the 2nd and 11th postoperative days. The systematic review retrieved a total of 34 articles after duplicates were removed. Finally, nine studies reporting on 23 patients were deemed eligible for our analysis. The average time to MAPCAs coiling was 12 days, while the mean hospital stay was 36 days. Conclusions: MAPCAs should be included in the differential diagnosis of ASO complicated by cardiac or respiratory failure, or pulmonary hemorrhage acutely postoperatively. Once managed, recovery of these patients is predictable, and mortality is low. Further studies investigating the diagnostic value of echocardiography and the long-term outcomes of these MAPCAs are necessary.
- Published
- 2022
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10. Importance of Preserved Tricuspid Valve Function for Effective Soft Robotic Augmentation of the Right Ventricle in Cases of Elevated Pulmonary Artery Pressure.
- Author
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Wamala I, Payne CJ, Saeed MY, Bautista-Salinas D, Van Story D, Thalhofer T, Staffa SJ, Ghelani SJ, Del Nido PJ, Walsh CJ, and Vasilyev NV
- Subjects
- Animals, Heart Ventricles surgery, Humans, Pulmonary Artery surgery, Swine, Tricuspid Valve diagnostic imaging, Tricuspid Valve surgery, Heart Failure therapy, Robotics, Tricuspid Valve Insufficiency diagnostic imaging, Tricuspid Valve Insufficiency surgery
- Abstract
Purpose: In clinical practice, many patients with right heart failure (RHF) have elevated pulmonary artery pressures and increased afterload on the right ventricle (RV). In this study, we evaluated the feasibility of RV augmentation using a soft robotic right ventricular assist device (SRVAD), in cases of increased RV afterload., Methods: In nine Yorkshire swine of 65-80 kg, a pulmonary artery band was placed to cause RHF and maintained in place to simulate an ongoing elevated afterload on the RV. The SRVAD was actuated in synchrony with the ventricle to augment native RV output for up to one hour. Hemodynamic parameters during SRVAD actuation were compared to baseline and RHF levels., Results: Median RV cardiac index (CI) was 1.43 (IQR, 1.37-1.80) L/min/m
2 and 1.26 (IQR 1.05-1.57) L/min/m2 at first and second baseline. Upon PA banding RV CI fell to a median of 0.79 (IQR 0.63-1.04) L/min/m2 . Device actuation improved RV CI to a median of 0.87 (IQR 0.78-1.01), 0.85 (IQR 0.64-1.59) and 1.11 (IQR 0.67-1.48) L/min/m2 at 5 min (p = 0.114), 30 min (p = 0.013) and 60 (p = 0.033) minutes respectively. Statistical GEE analysis showed that lower grade of tricuspid regurgitation at time of RHF (p = 0.046), a lower diastolic pressure at RHF (p = 0.019) and lower mean arterial pressure at RHF (p = 0.024) were significantly associated with higher SRVAD effectiveness., Conclusions: Short-term augmentation of RV function using SRVAD is feasible even in cases of elevated RV afterload. Moderate or severe tricuspid regurgitation were associated with reduced device effectiveness., (© 2021. The Author(s).)- Published
- 2022
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11. The feasibility of mitral valve device foldoplasty: an in vivo study to evaluate durable retention.
- Author
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Wamala I, Saeed MY, Hammer PE, Bautista-Salinas D, Gauvreau K, Ghelani SJ, Vasilyev NV, and Del Nido PJ
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- Animals, Feasibility Studies, Mitral Valve diagnostic imaging, Mitral Valve surgery, Swine, Cardiac Surgical Procedures methods, Mitral Valve Insufficiency diagnostic imaging, Mitral Valve Insufficiency surgery, Mitral Valve Prolapse surgery
- Abstract
Objectives: We have previously shown in experimental settings that a leaflet foldoplasty device reduces redundant leaflet area to re-establish mitral valve (MV) coaptation. The current study investigates the in vivo device retention and functional durability following foldoplasty., Methods: The prototype is of superelastic nitinol formed into a 3-dimensional shape. It is unfolded to engage a specified area of leaflet tissue and then folded to exclude this tissue from the coaptation surface. Design modifications were made and tested in benchtop studies to determine the optimal design for durable retention within the leaflet. To evaluate in vivo performance, posterior leaflet chordae were severed in Yorkshire pigs to produce complete posterior leaflet prolapse and severe mitral regurgitation. Design modifications were then used for MV repair. Five animals that underwent repair using the optimal design were observed for 2 weeks postoperative to evaluate the functional result and implant retention., Results: Device position and orientation were maintained at 2 weeks while preserving the functional MV repair in all 5 animals. Coaptation height was 5.5 ± 1.5 mm, which was not significantly different from a baseline of 4.9 ± 0.8 mm. The degree of leaflet excursion was 41.0 ± 16.0 compared to a baseline of 58.7 ± 27.5., Conclusions: Device foldoplasty is a new concept for MV repair based on the reduction of redundant leaflet tissue area. This study demonstrates the feasibility of safe maintenance of this repair without early dislodgement or embolization., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
- Published
- 2022
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12. Autogenous mitochondria transplantation for treatment of right heart failure.
- Author
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Weixler V, Lapusca R, Grangl G, Guariento A, Saeed MY, Cowan DB, Del Nido PJ, McCully JD, and Friehs I
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- Animals, Cells, Cultured, Male, Myocytes, Cardiac cytology, Swine, Heart Failure surgery, Mitochondria transplantation, Transplantation, Autologous
- Abstract
Background: Right ventricular hypertrophy and failure are major causes of cardiac morbidity and mortality. A key event in the progression to right ventricular hypertrophy and failure is cardiomyocyte apoptosis due to mitochondrial dysfunction. We sought to determine whether localized intramyocardial injection of autologous mitochondria from healthy muscle treats heart failure., Methods: Mitochondria transplanted from different sources were initially tested in cultured hypertrophic cardiomyocytes. A right ventricular hypertrophy/right ventricular failure model created through banding of the pulmonary artery in immature piglets was used for treatment with autologous mitochondria (pulmonary artery banded mitochondria injected/treated n = 6) from calf muscle, versus vehicle (pulmonary artery banded vehicle injected/treated n = 6) injected into the right ventricular free-wall, and compared with sham-operated controls (sham, n = 6). Animals were followed for 8 weeks by echocardiography (free-wall thickness, contractility), and dp/dt max was measured concomitantly with cardiomyocyte hypertrophy, fibrosis, and apoptosis at study end point., Results: Internalization of mitochondria and adenosine triphosphate levels did not depend on the source of mitochondria. At 4 weeks, banded animals showed right ventricular hypertrophy (sham: 0.28 ± 0.01 cm vs pulmonary artery banding: 0.4 ± 0.02 cm wall thickness; P = .001), which further increased in pulmonary artery banded mitochondria injected/treated but declined in pulmonary artery banded vehicle injected/treated (0.47 ± 0.02 cm vs 0.348 ± 0.03 cm; P = .01). Baseline contractility was not different but was significantly reduced in pulmonary artery banded vehicle injected/treated compared with pulmonary artery banded mitochondria injected/treated and so was dp/dtmax. There was a significant difference in apoptotic cardiomyocyte loss and fibrosis in sham versus hypertrophied hearts with most apoptosis in pulmonary artery banded vehicle injected/treated hearts (sham: 1 ± 0.4 vs calf muscle vs vehicle: 13 ± 1.7; P = .001 and vs pulmonary artery banded mitochondria injected/treated: 8 ± 1.9, P = .01; pulmonary artery banded vehicle injected/treated vs pulmonary artery banded mitochondria injected/treated, P = .05)., Conclusions: Mitochondrial transplantation allows for prolonged physiologic adaptation of the pressure-loaded right ventricular and preservation of contractility by reducing apoptotic cardiomyocyte loss., (Copyright © 2020 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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13. A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion.
- Author
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Doulamis IP, Guariento A, Saeed MY, Nomoto RS, Duignan T, Del Nido PJ, and McCully JD
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- Acute Kidney Injury physiopathology, Animals, Arterial Occlusive Diseases physiopathology, Disease Models, Animal, Kidney blood supply, Kidney pathology, Kidney physiopathology, Kidney Function Tests, Male, Renal Artery physiopathology, Reperfusion Injury pathology, Reperfusion Injury physiopathology, Swine, Acute Kidney Injury etiology, Acute Kidney Injury pathology, Arterial Occlusive Diseases complications, Renal Artery pathology
- Abstract
Acute kidney injury (AKI) is associated with higher risk for morbidity and mortality post-operatively. Ischemia-reperfusion injury (IRI) is the most common cause of AKI. To mimic this clinical scenario, this study presents a highly reproducible large animal model of renal IRI in swine using temporary percutaneous bilateral balloon-catheter occlusion of the renal arteries. The renal arteries are occluded for 60 min by introducing the balloon-catheters through the femoral and carotid artery and advancing them into the proximal portion of the arteries. Iodinated contrast is injected in the aorta to assess any opacification of the kidney vessels and confirm the success of the artery occlusion. This is furtherly confirmed by the flattening of the pulse waveform at the tip of the balloon catheters. The balloons are deflated and removed after 60 min of bilateral renal artery occlusion, and the animals are allowed to recover for 24 h. At the end of the study, plasma creatinine and blood urea nitrogen significantly increase, while eGFR and urine output significantly decrease. The need for iodinated contrast is minimal and does not affect renal function. Bilateral renal artery occlusion better mimics the clinical scenario of perioperative renal hypoperfusion, and the percutaneous approach minimizes the impact of the inflammatory response and the risk of infection seen with an open approach, such as a laparotomy. The ability to create and reproduce this clinically relevant swine model eases the clinical translation to humans.
- Published
- 2021
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14. TGF-β1 Gene Polymorphism and Its Correlation with Serum Level of TGF-β1 in Psoriasis Vulgaris Among Iraqi People.
- Author
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Ahmed BT, Saeed MY, Noori SH, and Amin DM
- Abstract
Purpose: Many cytokines have been implicated in the pathogenesis of psoriasis, among these the transforming growth factor-beta 1 (TGF-β1) can be endorsed by different mechanisms besides inhibiting keratinocytes proliferation. The role of genetic polymorphisms of TGF-β1 has been studied in various inflammatory diseases. Our aim is to study the correlation of TGF-β1 gene polymorphism at codon 10 and 25 with the expression of serum level of TGF-β1 in a sample of Iraqi psoriatic patients compared to the control group., Materials and Methods: A cross-sectional study involved 100 patients with psoriasis vulgaris and 50 sex- and age-matched healthy volunteers as control group. Serum and genomic DNA were prepared from peripheral blood samples. Amplification refractory mutation system-polymerase chain reaction technique (ARMS-PCR) had been applied for genotyping TGF-β1 codon 10 [rs1982073] and codon 25 [rs1800471] genetic polymorphisms. Enzyme-linked immunosorbent assay technique (ELISA) based on the sandwich principle was used for quantification of serum TGF-β1 level. Psoriasis Area and Severity Index (PASI) scoring was applied for determining the severity in psoriatic patients and classified accordingly to mild (PASI<7), moderate (PASI 7-12), severe (PASI>12) groups., Results: Statistically significant difference was found in TGF-β1 gene polymorphism between psoriatic patients and control group at codon 10 (T869C) polymorphism (p=0.021) and codon 25 (G915C) polymorphism (p=0.040). No significant association was detected with the mean serum TGF-β1 level, severity of the disease, disease onset, gender, history of psoriatic arthritis, and smoking in both codons. Significant lower mean serum TGF-β1 level was found among psoriatic group (192.17 ± 531.12 ng/L) compared with controls (565.89 ± 1372.30 ng/L) (p = 0.018). Relation of mean serum TGF-β1 level with the onset of the disease was statistically significant (p = 0.004), early-onset disease group was lower (105.92 ± 68.02 ng/L) compared with the late-onset disease group (450.92 ±1027.79 ng/L). The mean serum TGF-β1 level showed no significant differences with the severity of psoriasis, gender, history of psoriatic arthritis, and smoking., Conclusion: Iraqi population showed a significant association between TGF-β1 gene polymorphism at codon 10 and 25 were with psoriasis susceptibility, and a significantly lower mean serum TGF-β1 level was detected in psoriatic patients., Competing Interests: The authors report no conflicts of interest in this work., (© 2020 Ahmed et al.)
- Published
- 2020
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15. Mitochondrial transplantation for myocardial protection in ex-situ‒perfused hearts donated after circulatory death.
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Guariento A, Doulamis IP, Duignan T, Kido T, Regan WL, Saeed MY, Hoganson DM, Emani SM, Fynn-Thompson F, Matte GS, Del Nido PJ, and McCully JD
- Subjects
- Animals, Disease Models, Animal, Female, Swine, Heart Transplantation methods, Mitochondria, Heart transplantation, Perfusion methods, Tissue Donors
- Abstract
Background: Donation after circulatory death (DCD) offers an additional source of cardiac allografts, potentially allowing expansion of the donor pool, but is limited owing to the effects of ischemia. In this study, we investigated the efficacy of mitochondrial transplantation to enhance myocardial function of DCD hearts., Methods: Circulatory death was induced in Yorkshire pigs (40-50 kg, n = 29) by a cessation of mechanical ventilation. After 20 minutes of warm ischemia, cardioplegia was administered. The hearts were then reperfused on an ex-situ blood perfusion system. After 15 minutes of reperfusion, hearts received either vehicle alone (vehicle [VEH], 10 ml; n = 8) or vehicle containing autologous mitochondria (vehicle with mitochondria as a single injection [MT], 5 × 10
9 in 10 ml, n = 8). Another group of hearts (serial injection of mitochondria [MTS ]; n = 6) received a second injection of mitochondria (5 × 109 in 10 ml) after 2 hours of ex-situ heart perfusion and reperfused for an additional 2 hours. A Sham group (sham hearts; n = 6) did not undergo any warm ischemia., Results: At the end of 4 hours of reperfusion, MT and MTS groups showed a significantly increased left ventricle/ventricular peak developed pressure (p = 0.002), maximal left ventricle/ventricular pressure rise (p < 0.001), fractional shortening (p < 0.001), and myocardial oxygen consumption (p = 0.004) compared with VEH. Infarct size was significantly decreased in MT and MTS groups compared with VEH (p < 0.001). No differences were found in arterial lactate levels among or within groups throughout reperfusion., Conclusions: Mitochondrial transplantation significantly preserves myocardial function and oxygen consumption in DCD hearts, thus providing a possible option for expanding the heart donor pool., (Copyright © 2020 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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16. Mitochondrial transplantation by intra-arterial injection for acute kidney injury.
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Doulamis IP, Guariento A, Duignan T, Kido T, Orfany A, Saeed MY, Weixler VH, Blitzer D, Shin B, Snay ER, Inkster JA, Packard AB, Zurakowski D, Rousselle T, Bajwa A, Parikh SM, Stillman IE, Del Nido PJ, and McCully JD
- Subjects
- Animals, Female, Injections, Intra-Arterial, Swine, Acute Kidney Injury therapy, Mitochondria transplantation, Reperfusion Injury therapy
- Abstract
Acute kidney injury is a common clinical disorder and one of the major causes of morbidity and mortality in the postoperative period. In this study, the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury were investigated. Female Yorkshire pigs underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon catheters. Following 60 min of ischemia, the balloon catheters were deflated and animals received either autologous mitochondria suspended in vehicle or vehicle alone, delivered as a single bolus to the renal arteries. The injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of the cortex and medulla. There were no safety-related issues detected with mitochondrial transplantation. Following 24 h of reperfusion, estimated glomerular filtration rate and urine output were significantly increased while serum creatinine and blood urea nitrogen were significantly decreased in swine that received mitochondria compared with those that received vehicle. Gross anatomy, histopathological analysis, acute tubular necrosis scoring, and transmission electron microscopy showed that the renal cortex of the vehicle-treated group had extensive coagulative necrosis of primarily proximal tubules, while the mitochondrial transplanted kidney showed only patchy mild acute tubular injury. Renal cortex IL-6 expression was significantly increased in vehicle-treated kidneys compared with the kidneys that received mitochondrial transplantation. These results demonstrate that mitochondrial transplantation by intra-arterial injection provides renal protection from ischemia-reperfusion injury, significantly enhancing renal function and reducing renal damage.
- Published
- 2020
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17. Dynamic Augmentation of Left Ventricle and Mitral Valve Function With an Implantable Soft Robotic Device.
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Saeed MY, Van Story D, Payne CJ, Wamala I, Shin B, Bautista-Salinas D, Zurakowski D, Del Nido PJ, Walsh CJ, and Vasilyev NV
- Abstract
Left ventricular failure is strongly associated with secondary mitral valve regurgitation. Implantable soft robotic devices are an emerging technology that enables augmentation of a native function of a target tissue. We demonstrate the ability of a novel soft robotic ventricular assist device to dynamically augment left ventricular contraction, provide native pulsatile flow, simultaneously reshape the mitral valve apparatus, and eliminate the associated regurgitation in an Short-term large animal model of acute left ventricular systolic dysfunction., (© 2020 The Authors.)
- Published
- 2020
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18. A geometrically adaptable heart valve replacement.
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Hofferberth SC, Saeed MY, Tomholt L, Fernandes MC, Payne CJ, Price K, Marx GR, Esch JJ, Brown DW, Brown J, Hammer PE, Bianco RW, Weaver JC, Edelman ER, and Del Nido PJ
- Subjects
- Heart Valves, Prosthesis Design, Cardiac Surgical Procedures, Heart Valve Prosthesis
- Abstract
Congenital heart valve disease has life-threatening consequences that warrant early valve replacement; however, the development of a growth-accommodating prosthetic valve has remained elusive. Thousands of children continue to face multiple high-risk open-heart operations to replace valves that they have outgrown. Here, we demonstrate a biomimetic prosthetic valve that is geometrically adaptable to accommodate somatic growth and structural asymmetries within the heart. Inspired by the human venous valve, whose geometry is optimized to preserve functionality across a wide range of constantly varying volume loads and diameters, our balloon-expandable synthetic bileaflet valve analog exhibits similar adaptability to dimensional and shape changes. Benchtop and acute in vivo experiments validated design functionality, and in vivo survival studies in growing sheep demonstrated that mechanical valve expansion accommodated growth. As illustrated in this work, dynamic size adaptability with preservation of unidirectional flow in prosthetic valves thus offers a paradigm shift in the treatment of heart valve disease., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2020
- Full Text
- View/download PDF
19. A Novel Biological Strategy for Myocardial Protection by Intracoronary Delivery of Mitochondria: Safety and Efficacy.
- Author
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Shin B, Saeed MY, Esch JJ, Guariento A, Blitzer D, Moskowitzova K, Ramirez-Barbieri G, Orfany A, Thedsanamoorthy JK, Cowan DB, Inkster JA, Snay ER, Staffa SJ, Packard AB, Zurakowski D, Del Nido PJ, and McCully JD
- Abstract
Mitochondrial dysfunction is the determinant insult of ischemia-reperfusion injury. Autologous mitochondrial transplantation involves supplying one's healthy mitochondria to the ischemic region harboring damaged mitochondria. The authors used in vivo swine to show that mitochondrial transplantation in the heart by intracoronary delivery is safe, with specific distribution to the heart, and results in significant increase in coronary blood flow, which requires intact mitochondrial viability, adenosine triphosphate production, and, in part, the activation of vascular K
IR channels. Intracoronary mitochondrial delivery after temporary regional ischemia significantly improved myocardial function, perfusion, and infarct size. The authors concluded that intracoronary delivery of mitochondria is safe and efficacious therapy for myocardial ischemia-reperfusion injury., (© 2019 The Authors.)- Published
- 2019
- Full Text
- View/download PDF
20. The use of povidone-iodine and hydrogen peroxide mixture as an adjunct to non-surgical treatment of slight to moderate chronic periodontitis.
- Author
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Al-Saeed MY and Babay N
- Abstract
Objective: The aim of this study was to evaluate the clinical effects of the adjunctive use of povidone-iodine with or without hydrogen peroxide as coolant and disinfectant during ultrasonic scaling and root planing in the treatment of chronic periodontitis., Materials and Methods: Sixteen patients initially participated in the study. Thirteen patients (8 males and 5 females) completed the 3-month follow-up period. Their mean (±SD) age was 42.92 ± 7.55 years. In each experimental subject, the mouth was split into four quadrants. A randomly selected quadrant was chosen to receive one of the three treatment group modalities which were: Group 1 - ultrasonic scaling and root planing plus irrigation with 1% povidone-iodine and 3.0% hydrogen peroxide mixture; Group 2 - ultrasonic scaling and root planing plus irrigation with 1% povidone-iodine; Group 3 - ultrasonic scaling and root planing plus irrigation with normal saline. The fourth quadrant served as a control group., Results: At the 3-month evaluation, there was no significant difference between the three treatment groups in terms of probing depth reduction, clinical attachment gain, gingival recession increase, reduction in the bleeding upon probing or plaque score reduction (P > 0.05). However, the three treatment groups had statistically significant higher mean reduction in the probing depth, gain in the clinical attachment level and reduction in the bleeding upon probing than the control group (P < 0.05)., Conclusion: There were no added benefits of using a mixture of povidone-iodine and hydrogen peroxide or povidone-iodine as disinfectants during ultrasonic scaling and root planing in the treatment of chronic periodontitis.
- Published
- 2009
- Full Text
- View/download PDF
21. Concomitant tuberculosis and hydatid cyst in a solitary pulmonary nodule of left lower lobe.
- Author
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Saeed MY, Ahmed AH, Elhassan NB, and Elhassan AM
- Abstract
We report a case of a 25-year-old woman who presented with recurrent attacks of haemoptysis over a 12 month period. Physical examination was normal. Chest x ray and computed tomography scan showed a 2.6×1.9 cm pulmonary nodule. Full blood count and biochemical profile were normal. Fibreoptic bronchoscopy was normal and bronchial aspirate was negative for Ziehl-Neelsen staining and malignant cells. The nodule was removed surgically because it was feared that it could be malignant. Histology showed concomitant hydatid disease and tuberculosis. This is a rare occurrence with only one similar case reported in the literature.
- Published
- 2009
- Full Text
- View/download PDF
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