Papers by Giovanna Ramirez Barbieri
Circulation, 2017
Introduction: Autologous mitochondrial transplantation by direct injection has shown to be cardio... more Introduction: Autologous mitochondrial transplantation by direct injection has shown to be cardioprotective in ischemic injury. Herein, we investigate a novel mode of mitochondrial transplantation ...
JACC: Basic to Translational Science, 2019
The Journal of Heart and Lung Transplantation, 2018
confirm external STS in any of the patients and thus were presumed to have internal STS and were ... more confirm external STS in any of the patients and thus were presumed to have internal STS and were all placed on ungrounded cable. After a mean follow up of 4 years, there were no deaths, 1 patient had a transplant and 1 patient had a pump exchange, both of which were not due to STS. Conclusion: A conservative approach of external driveline replacement and using ungrounded cable appears to be safe in the management of STS while avoiding the need for pump exchange.
Circulation, 2017
Introduction: Autologous mitochondrial transplantation by direct injection has shown to be cardio... more Introduction: Autologous mitochondrial transplantation by direct injection has shown to be cardioprotective in ischemic injury. Herein, we investigate a novel mode of mitochondrial transplantation ...
JACC: Basic to Translational Science, 2019
The Journal of Heart and Lung Transplantation, 2018
confirm external STS in any of the patients and thus were presumed to have internal STS and were ... more confirm external STS in any of the patients and thus were presumed to have internal STS and were all placed on ungrounded cable. After a mean follow up of 4 years, there were no deaths, 1 patient had a transplant and 1 patient had a pump exchange, both of which were not due to STS. Conclusion: A conservative approach of external driveline replacement and using ungrounded cable appears to be safe in the management of STS while avoiding the need for pump exchange.
American Journal of Physiology-Lung Cellular and Molecular Physiology, 2019
The most common cause of acute lung injury is ischemia-reperfusion injury (IRI), during which mit... more The most common cause of acute lung injury is ischemia-reperfusion injury (IRI), during which mitochondrial damage occurs. We have previously demonstrated that mitochondrial transplantation is an efficacious therapy to replace or augment mitochondria damaged by IRI, allowing for enhanced muscle viability and function in cardiac tissue. Here, we investigate the efficacy of mitochondrial transplantation in a murine lung IRI model using male C57BL/6J mice. Transient ischemia was induced by applying a microvascular clamp on the left hilum for 2 h. Upon reperfusion mice received either vehicle or vehicle-containing mitochondria either by vascular delivery (Mito V) through the pulmonary artery or by aerosol delivery (Mito Neb) via the trachea (nebulization). Sham control mice underwent thoracotomy without hilar clamping and were ventilated for 2 h before returning to the cage. After 24 h recovery, lung mechanics were assessed and lungs were collected for analysis. Our results demonstrated...
The Journal of Thoracic and Cardiovascular Surgery, 2019
Objective: To investigate preischemic intracoronary autologous mitochondrial transplantation (MT)... more Objective: To investigate preischemic intracoronary autologous mitochondrial transplantation (MT) as a therapeutic strategy for prophylactic myocardial protection in a porcine model of regional ischemia-reperfusion injury (IRI). Methods: The left coronary artery was cannulated in Yorkshire pigs (n ¼ 26). Mitochondria (1 3 10 9) or buffer (vehicle [Veh]) were delivered as a single bolus (MT S) or serially (10 injections over 60 minutes; MT SS). At 15 minutes after injection, the heart was subjected to temporary regional ischemia (RI) by snaring the left anterior descending artery. After 30 minutes of RI, the snare was released, and the heart was reperfused for 120 minutes. Results: Coronary blood flow (CBF) and myocardial function were increased temporarily during the pre-RI period. Following 30 minutes of RI, MT S and MT SS hearts had significantly increased CBF that persisted throughout reperfusion (Veh vs MT S and MT SS ; P ¼ .04). MT S and MT SS showed a significantly enhanced ejection fraction (Veh vs MT S ,
The Annals of Thoracic Surgery, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Journal of Vascular Surgery, 2019
Objective: Acute limb ischemia (ALI), the most challenging form of ischemia-reperfusion injury (I... more Objective: Acute limb ischemia (ALI), the most challenging form of ischemia-reperfusion injury (IRI) in skeletal muscle tissue, leads to decreased skeletal muscle viability and limb function. Mitochondrial injury has been shown to play a key role in skeletal muscle IRI. In previous studies, we have demonstrated that mitochondrial transplantation (MT) is an efficacious therapeutic strategy to replace or to augment mitochondria damaged by IRI, allowing enhanced muscle viability and function in cardiac tissue. In this study, we investigated the efficacy of MT in a murine ALI model. Methods: C57BL/6J mice (male, 10-12 weeks) were used in a model of ALI. Ischemia was induced by applying a tourniquet on the left hindlimb. After 2 hours of ischemia, the tourniquet was released, and reperfusion of the hindlimb was reestablished; either vehicle alone (n ¼ 15) or vehicle containing mitochondria (n ¼ 33) was injected directly into all the muscles of the hindlimb. Mitochondria were delivered at concentrations of 1 Â 10 6 to 1 Â 10 9 per gram wet weight to each muscle, and the animals were allowed to recover. Sham mice received no ischemia or injections but were anesthetized for 2 hours and allowed to recover. After 24 hours of recovery, limb function was assessed by DigiGait (Mouse Specifics Inc, Boston, Mass), and animals were euthanized; the gastrocnemius, soleus, and vastus medialis muscles were collected for analysis. Results: After 24 hours of hindlimb reperfusion, infarct size (percentage of total mass) and apoptosis were significantly decreased (P < .001, each) in the gastrocnemius, soleus, and vastus medialis muscles in MT mice compared with vehicle mice for all mitochondrial concentrations (1 Â 10 6 to 1 Â 10 9 per gram wet weight). DigiGait analysis at 24 hours of reperfusion showed that percentage shared stance time was significantly increased (P < .001) and stance factor was significantly decreased (P ¼ .001) in vehicle compared with MT and sham mice. No significant differences in percentage shared stance time (P ¼ .160) or stance factor (P ¼ .545) were observed between MT and sham mice. Conclusions: MT ameliorates skeletal muscle injury and enhances hindlimb function in the murine model of ALI. (J Vasc Surg 2019;-:1-13.) Clinical Relevance: Acute limb ischemia (ALI) is the most challenging form of ischemia-reperfusion injury (IRI), leading to loss of muscle viability and function. Mitochondria have been shown to play a key role in IRI. Previously, we have demonstrated that mitochondrial transplantation (MT) is an efficacious therapy to replace or to augment mitochondria damaged by IRI in cardiac tissue. In this study, we demonstrate that MT significantly decreases infarct size and apoptosis and significantly enhances hindlimb function in a murine model of ALI. MT provides a novel therapy for ALI, allowing preservation of muscle viability and muscle function.
Mitochondrion, 2018
Previously, we have demonstrated that the transplantation of autologous mitochondria is cardiopro... more Previously, we have demonstrated that the transplantation of autologous mitochondria is cardioprotective. No immune or autoimmune response was detectable following the single injection of autologous mitochondria. To expand the therapeutic potential and safety of mitochondrial transplantation, we now investigate the immune response to single and serial injections of syngeneic and allogeneic mitochondria delivered by intraperitoneal injection. Our results demonstrate that there is no direct or indirect, acute or chronic alloreactivity, allorecognition or damage-associated molecular pattern molecules (DAMPs) reaction to single or serial injections of either syngeneic or allogeneic mitochondria.
The Journal of Heart and Lung Transplantation, 2018
BACKGROUND-Cold ischemia time (CIT) causes ischemia-reperfusion injury to the mitochondria and de... more BACKGROUND-Cold ischemia time (CIT) causes ischemia-reperfusion injury to the mitochondria and detrimentally effects myocardial function and tissue viability. Mitochondrial transplantation replaces damaged mitochondria and enhances myocardial function and tissue viability. Herein, we investigate the efficacy of mitochondrial transplantation in enhancing graft function and viability after prolonged CIT. METHODS-Heterotopic heart transplantation was performed in C57BL/6J mice. Upon heart harvesting from C57BL/6J donors, 0.5 mL of either mitochondria (1 × 10 8 in respiration buffer; Mitochondria) or respiration buffer (Vehicle) was delivered antegrade to the coronary arteries via injection to the coronary ostium. The hearts were excised and preserved for 29 ± 0.3 hours in cold saline (4°C). The hearts were heterotopically transplanted. A second injection of either mitochondria (1 × 10 8) or respiration buffer (Vehicle) was delivered antegrade to the coronary arteries 5 minutes after transplantation. Grafts were analyzed for 24 hours. Beating score, graft function and tissue injury were measured. RESULTS-Beating score, calculated ejection fraction and shortening fraction were significantly enhanced (P < 0.05), while necrosis and neutrophil infiltration were significantly decreased (P < Conflict of Interest statement Dr. McCully, Dr. Cowan and Dr. del Nido have patents pending for the isolation and usage of mitochondria. There are no other conflicts of interest by any of the authors. The authors attest they had full freedom to explore the data, analyze the results independent from any sponsor and that they had sole authority to make the final decision to submit the material for publication.
Circulation, 2017
Introduction: Autologous mitochondrial transplantation has been shown to be efficacious in cardia... more Introduction: Autologous mitochondrial transplantation has been shown to be efficacious in cardiac ischemia/reperfusion injury. We now provide evidence that single or multiple injections of autogen...
Esta publicación es posible gracias al apoyo del Colegio Médico del Perú a través de Fondo Editor... more Esta publicación es posible gracias al apoyo del Colegio Médico del Perú a través de Fondo Editorial Comunicacional.
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Papers by Giovanna Ramirez Barbieri