Brain and Spinal Cord Lesions with Long-Term Total Artificial Heart Pumping

Two surgical techniques have been developed in our laboratory to deal with identifiable problems in long-term artificial heart experiments. A right thoracotomy is used to deal with problems such as extensive bleeding, which occur in the immediate postoperative stage of the experiment, while a left thoracotomy is used in cases in Which the original implantation is preceded by more than one week, since extensive adhesions complicate the right thoracotomy at that stage. Pulmonary problems have been eliminated as a primary cause of difficulties after reoperation, but infection remains a serious problem.

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Complete Correction of Brain and Spinal Cord Pathology in Metachromatic Leukodystrophy Mice

Frontiers in Molecular Neuroscience ◽

10.3389/fnmol.2021.677895 ◽

2021 ◽

Vol 14 ◽

Author(s):

Emilie Audouard ◽

Valentin Oger ◽

Béatrix Meha ◽

Nathalie Cartier ◽

Caroline Sevin ◽

...

Keyword(s):

Spinal Cord ◽

Gene Therapy ◽

Metachromatic Leukodystrophy ◽

Early Death ◽

Lysosomal Storage ◽

Adeno Associated Virus ◽

Virus Serotype ◽

Brain And Spinal Cord ◽

Sulfatide Accumulation

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder characterized by accumulation of sulfatides in both glial cells and neurons. MLD results from an inherited deficiency of arylsulfatase A (ARSA) and myelin degeneration in the central and peripheral nervous systems. Currently, no effective treatment is available for the most frequent late infantile (LI) form of MLD after symptom onset. The LI form results in rapid neurological degradation and early death. ARSA enzyme must be rapidly and efficiently delivered to brain and spinal cord oligodendrocytes of patients with LI MLD in order to potentially stop the progression of the disease. We previously showed that brain gene therapy with adeno-associated virus serotype rh10 (AAVrh10) driving the expression of human ARSA cDNA alleviated most long-term disease manifestations in MLD mice but was not sufficient in MLD patient to improve disease progression. Herein, we evaluated the short-term effects of intravenous AAVPHP.eB delivery driving the expression of human ARSA cDNA under the control of the cytomegalovirus/b-actin hybrid (CAG) promoter in 6-month-old MLD mice that already show marked sulfatide accumulation and brain pathology. Within 3 months, a single intravenous injection of AAVPHP.eB-hARSA-HA resulted in correction of brain and spinal cord sulfatide storage, and improvement of astrogliosis and microgliosis in brain and spinal cord of treated animals. These results strongly support to consider the use of AAVPHP.eB-hARSA vector for intravenous gene therapy in symptomatic rapidly progressing forms of MLD.

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'Scary' pericytes: the fibrotic scar in brain and spinal cord lesions

Trends in Neurosciences ◽

10.1016/j.tins.2021.10.013 ◽

2021 ◽

Author(s):

Nora H. Rentsch ◽

Ruslan Rust

Keyword(s):

Spinal Cord ◽

Spinal Cord Lesions ◽

Fibrotic Scar ◽

Brain And Spinal Cord

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The Total Artificial Heart

AACN Advanced Critical Care ◽

10.4037/15597768-1991-3022 ◽

1991 ◽

Vol 2 (3) ◽

pp. 587-597

Author(s):

Lawrence E. Barker

Keyword(s):

Artificial Heart ◽

Total Artificial Heart ◽

Thromboembolic Events ◽

Bridge To Transplant ◽

University Of Utah ◽

Cardiac Assistance ◽

Permanent Implants ◽

Mechanical Devices ◽

The University

In the early 1800s, an awareness of potential ventricular failure stimulated interest in artificial heart replacement. In 1937 the first total artificial heart (TAH) was implanted into the chest of a dog by Russian physicians. The primary driving force for mechanical cardiac assistance developed from the necessity for circulatory assistance in order to perform corrective cardiac surgery. In 1953 the first successful closure of an atrial septal defect using extracorporeal circulation was performed. During the following decade the concept of using mechanical devices to assist the failing heart was aggressively pursued. This culminated in the first implant of a TAH in a human in 1969 as a bridge to transplant. Clinical implant of the TAH as a permanent device was performed in 1982 by researchers at the University of Utah. This patient lived for 112 days. Three successive permanent implants were performed in Louisville, Kentucky, with one patient surviving for 620 days. All of these permanent TAH patients suffered from device-related complications including bleeding, infection, and thromboembolic events. It became apparent that the present configuration of the TAH with its external drive lines and large air console was not ideal for long-term support. In 1985 the first implant of the Symbion J-7-100 TAH (Jarvik-7) as a bridge to transplant was performed. This patient was supported by the device for 9 days and was successfully transplanted and discharged home. Since 1985 more than 170 patients have been bridged using the Symbion J-7 TAH with more than 70% of these patients being successfully transplanted. The incidence of thromboembolic events has dramatically reduced with better understanding of anticoagulation requirements. Infection continues to be the greatest potential complication with these patients. In spite of this, the pneumatic TAH has proved to be an adequate bridge to transplant device

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Baylor Multi-Purpose One-Piece Total Artificial Heart (TAH) System for Short-Term to Long-Term Use

Heart Replacement ◽

10.1007/978-4-431-67023-0_21 ◽

1993 ◽

pp. 153-160 ◽

Cited By ~ 2

Author(s):

Motomi Shiono ◽

Setsuo Takatani ◽

Tatsuya Sasaki ◽

Naoki Minato ◽

Yukihiko Orime ◽

...

Keyword(s):

Artificial Heart ◽

Total Artificial Heart ◽

Short Term

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The Applicability of Experimental Experience with the Total Artificial Heart to its Clinical Use

The International Journal of Artificial Organs ◽

10.1177/039139889201500510 ◽

1992 ◽

Vol 15 (5) ◽

pp. 307-311 ◽

Cited By ~ 3

Author(s):

J. Vašků ◽

P. Urbánek ◽

M. Dostál ◽

Jan Vašků

Keyword(s):

Clinical Application ◽

Artificial Heart ◽

Venous Pressure ◽

Early Period ◽

Total Artificial Heart ◽

Blood Coagulation Disorders ◽

Clinical Use ◽

Long Term Experiments ◽

Long Term Experiment

Long-term experiments with the total artificial heart (TAH) are a source of valuable knowledge for later clinical application. Our observations result from 66 long-term experiments on calves and one goat ranging from 30 to 314 days, which have shown the main possible complications in the early period (one month) and later in the experiment. Problems until the second month of pumping concern the clinical pendant of the TAH as a bridge for transplantation, i.e. surgical problems, blood coagulation disorders, infection etc. Later problems are high venous pressure or arterial hypertension, infection with septic thromboembolization, mineralization of the driving diaphragm, etc., and are more closely comparable to the conditions of permanent clinical use of the TAH. Faultless surgery, device function and the regimen of pumping are essential factors in every long-term experiment, just as in clinical application. Infection is a threat throughout any experiment, as in clinical cases. The TNS-BRNO-VII/clin/80 TAH has been implanted in six patients.

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