Article
Cardiac & Cardiovascular Systems
J. Trent Magruder, Stuart J. Weiss, Katie Gray DeAngelis, John Haddle, Nimesh D. Desai, Wilson Y. Szeto, Michael A. Acker
Summary: Low oxygen delivery (DO2) during cardiac surgery may be associated with morbidity and mortality, particularly in patients undergoing nonisolated coronary artery bypass grafting (CABG). These findings emphasize the importance of goal-directed perfusion strategies.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2022)
Article
Biotechnology & Applied Microbiology
Michelle Mendiola Pla, Yuting Chiang, Antonio Roki, Chunbo Wang, Franklin H. Lee, Matthew F. Smith, Ryan T. Gross, Jun-Neng Roan, Muath Bishawi, Amy Evans, Lynden E. Gault, Sam Ho, Carolyn Glass, Jacob N. Schroder, Paul Lezberg, Carmelo A. Milano, Dawn E. Bowles
Summary: This study demonstrates the feasibility and efficiency of delivering genes to porcine cardiac allografts utilizing adeno-associated viral vectors during ex vivo perfusion. Durable and dose-dependent transgene expression was achieved in the allografts, supporting the idea of gene therapy interventions to enhance transplantation outcomes.
HUMAN GENE THERAPY
(2023)
Article
Cardiac & Cardiovascular Systems
Alice Hayward, Alex Robertson, Timothy Thiruchelvam, Michael Broadhead, Victor T. Tsang, Neil J. Sebire, Richard W. Issitt
Summary: This study aimed to determine the oxygen delivery indexed to body surface area (DO2i) threshold associated with postoperative acute kidney injury (AKI) in pediatric patients undergoing cardiac surgery with cardiopulmonary bypass (CPB), and to assess its predictive importance in the presence of other known risk factors. The findings showed that cumulative time spent below a DO2i value of 350 mL/min/m2 was associated with AKI, and the DO2i threshold maintained predictive importance even when considering other risk factors. Patients who developed AKI after CPB were younger, had longer CPB and ischemic times, and required higher inotrope support.
JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY
(2023)
Article
Medicine, General & Internal
Mikhail Dodonov, Francesco Onorati, Giovanni Battista Luciani, Alessandra Francica, Maddalena Tessari, Tiziano Menon, Leonardo Gottin, Aldo Domenico Milano, Giuseppe Faggian
Summary: Using pulsatile flow during cardiopulmonary bypass results in significantly lower systemic and pulmonary vascular resistances, increased eNOS production, and better preservation of renal function. The clinical impact of increased vasopressor requirements in the pulsatile flow group warrants further evaluation.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Medicine, General & Internal
Chantal A. Boly, Margot Venhuizen, Nicole A. M. Dekker, Alexander B. A. Vonk, Christa Boer, Charissa E. van den Brom
Summary: Cardiac surgery with cardiopulmonary bypass impairs microcirculatory perfusion equally in metabolically healthy obese patients and lean patients, with recovery observed in both groups within three days post-surgery.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Anesthesiology
Michael Schoerghuber, Thomas Baernthaler, Florian Prueller, Polina Mantaj, Gerhard Cvirn, Wolfgang Toller, Christoph Klivinyi, Elisabeth Mahla, Akos Heinemann
Summary: Moderately hypothermic cardiopulmonary bypass during cardiac surgery induces platelet dysfunction, which can be restored by supplemental fibrinogen.
BRITISH JOURNAL OF ANAESTHESIA
(2023)
Article
Engineering, Biomedical
Nicole S. Wilder, Dean B. Andropoulos, Theron Paugh, Kathleen K. Kibler, Susan C. Nicolson, Athena F. Zuppa, Ganesh S. Moorthy
Summary: This study evaluated the disposition of DEX in ex vivo CPB circuits and found that circuit coating, temperature, and modified ultrafiltration (MUF) have an effect on DEX. The majority of DEX sequestration occurred within the first 15 minutes in the circuits. The dose and dosing scheme influenced the percent of DEX remaining in plasma pre- and post-MUF. MUF significantly increased the plasma concentration of DEX. A combination of initial loading dose and continuous infusion resulted in steady concentrations of DEX over 4 hours.
Article
Biotechnology & Applied Microbiology
Jonas Becker, Megan Lynn Stanifer, Sarah Rebecca Leist, Bettina Stolp, Olena Maiakovska, Ande West, Ellen Wiedtke, Kathleen Boerner, Ali Ghanem, Ina Ambiel, Longping Victor Tse, Oliver Till Fackler, Ralph Steven Baric, Steeve Boulant, Dirk Grimm
Summary: Multiple experiments have shown that AAV vectors co-expressing three short hairpin RNAs targeting the SARS-CoV-2 genes can effectively suppress virus infection and prevent viral escape mutations, holding great potential as a preventive or therapeutic antiviral measure for controlling the COVID-19 pandemic.
Article
Medicine, Research & Experimental
Cynthia D. Anderson, Jennifer Ataam Arthur, Yuan Zhang, Nike Bharucha, Ioannis Karakikes, Ralph V. Shohet
Summary: CRISPR-Cas9-based genome editing technologies have the potential for clinical translation, but delivering nucleic acids into target cells in vivo is challenging. This study presents a new method using focused ultrasound targeted microbubble destruction to deliver CRISPR-Cas9 base editing vectors to the mouse liver. The results demonstrate successful base editing in mouse liver cells, but with lower specificity and more off-target base exchange in vivo.
MOLECULAR THERAPY NUCLEIC ACIDS
(2023)
Review
Medicine, General & Internal
Claire Goumard, Celia Turco, Mehdi Sakka, Lynda Aoudjehane, Philippe Lesnik, Eric Savier, Filomena Conti, Olivier Scatton
Summary: The ongoing organ shortage has led transplant teams to develop ex-situ machine perfusion as an alternative source for liver grafts. Normothermic machine perfusion has shown promise in defatting livers, with successful results on human organs.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Cardiac & Cardiovascular Systems
Mats T. Vervoorn, Jantijn J. G. J. Amelink, Elisa M. Ballan, Pieter A. Doevendans, Joost P. G. Sluijter, Mudit Mishra, Gerard J. J. Boink, Dawn E. Bowles, Niels P. van der Kaaij
Summary: Machine perfusion for ex situ organ preservation improves organ transplantation outcomes and potentially allows for selective immunomodulation, ischemia-reperfusion injury tolerance, and correction of genetic defects. Gene modifying therapies during ex situ heart perfusion offer promising treatment options for heart diseases caused by pathogenic mutations.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Article
Multidisciplinary Sciences
Parag N. Jain, Matthew Robertson, Javier J. Lasa, Lara Shekerdemian, Danielle Guffey, Yuhao Zhang, Krithika Lingappan, Paul Checchia, Cristian Coarfa
Summary: The study explored differential gene expression profiles in neonates with HLHS who develop LCOS after CPB, revealing significant changes in inflammatory and metabolic pathways. This opens up new possibilities for identifying potential therapeutic targets in this high-risk population.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Khin M. Noe, Andrea Don, Andrew D. Cochrane, Michael Z. L. Zhu, Jennifer P. Ngo, Julian A. Smith, Amanda G. Thrift, Johnny Vogiatjis, Andrew Martin, Rinaldo Bellomo, James McMillan, Roger G. Evans
Summary: A study investigated the effect of hemodynamic management during cardiac surgery on the risk of postoperative acute kidney injury (AKI), and found no difference in blood pressure and pump flow between patients who did and did not develop AKI. In a small-scale trial, it was found that increasing the target pump flow and mean arterial pressure (MAP) improved the mean pump flow and systemic oxygen delivery, but did not alter the MAP during cardiopulmonary bypass (CPB). Further large-scale trials are needed to evaluate the impact of these variables on the risk of AKI.
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
(2023)
Article
Materials Science, Multidisciplinary
Yaqian Fan, Peilang Yang, Hongyang Ma, Yan Liu, Xiaokang Ding, Yang Hu, Gang Cheng, Fu-Jian Xu
Summary: A ternary nucleic acid delivery system (HPD) was developed to address the challenges in wound gene therapy, including cytokine deficiency, substantial exudation, and difficult transfection. The study demonstrated that HPD had low toxicity and high transfection efficiency in cell lines/primary cells, and showed excellent performance in in vivo and ex vivo therapy of severe skin wounds. This research provides a highly efficient and reproducible delivery system for wound gene therapy, with potential applications in other clinical scenarios.
Review
Biochemistry & Molecular Biology
Xiaomo Wu, Xiaorong He, Fahui Liu, Xiaochang Jiang, Ping Wang, Jinyan Zhang, Ju Jiang
Summary: Retroviral gene therapy shows promise in treating multiple human diseases. It offers long-term therapeutic benefits through genetic correction and alteration. Advances in retroviral vector engineering, genomic editing, synthetic biology, and immunology will expand the applications of gene therapy and improve treatment efficacy and safety. Genetically engineered hematopoietic stem cells (HSCs) have achieved marketing approval for various pathological conditions, while gene editing is explored as an alternative therapeutic approach.
COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL
(2022)
Article
Cardiac & Cardiovascular Systems
Andrew B. Harvey, Renelyn A. Woltes, Raymond N. Deepe, Hannah G. Tarolli, Jenna R. Drummond, Allison Trouten, Auva Zandi, Jeremy L. Barth, Rupak Mukherjee, Martin J. Romeo, Silvia G. Vaena, Ge Tao, Robin Muise-Helmericks, Paula S. Ramos, Russell A. Norris, Andy Wessels
Summary: This study highlights the importance of SOX9 in the regulation of epicardial cell invasion and emphasizes the role of EPDCs in regulating atrioventricular valve development and homeostasis. It also reports a novel expression profile of Cd109, a gene with previously unknown relevance in heart development.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Review
Cardiac & Cardiovascular Systems
MariaSanta C. Mangione, Jinhua Wen, Dian J. Cao
Summary: mTOR, a mechanistic target of rapamycin, is an evolutionarily conserved pathway that plays a fundamental role in nutrient sensing, growth, metabolism, lifespan, and aging. Recent studies have highlighted the regulatory role of mTOR in innate immune responses and its involvement in the pathogenesis of cardiovascular diseases, especially in acute inflammation and atherosclerotic cardiovascular disease. This review also discusses mTOR's role in trained immunity, immune senescence, and clonal hematopoiesis, as well as its architecture and regulatory complexes.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Junlin Li, Yajun Gong, Yiren Wang, Huihui Huang, Huan Du, Lianying Cheng, Cui Ma, Yongxiang Cai, Hukui Han, Jianhong Tao, Gang Li, Panke Cheng
Summary: Myocardial ischemia-reperfusion injury is closely related to the final infarct size in acute myocardial infarction. Regulatory T cells play an important role in the inflammatory response after AMI, but different subtypes of Tregs have different effects on the injury.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)
Article
Cardiac & Cardiovascular Systems
Yuxin Chu, Yutao Hua, Lihao He, Jin He, Yunxi Chen, Jing Yang, Ismail Mahmoud, Fanfang Zeng, Xiaochang Zeng, Gloria A. Benavides, Victor M. Darley-Usmar, Martin E. Young, Scott W. Ballinger, Sumanth D. Prabhu, Cheng Zhang, Min Xie
Summary: This study demonstrates that administering beta-hydroxybutyrate (beta-OHB) at the time of reperfusion can reduce infarct size and preserve cardiac function by activating autophagy and preserving mitochondrial homeostasis, potentially through mTOR inhibition.
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2024)