scholarly journals De Novo Valve Tissue Morphology Following Bioscaffold Mitral Valve Replacement in a Juvenile Non-Human Primate Model

2021 ◽  
Vol 8 (7) ◽  
pp. 100
Author(s):  
Brittany A. Gonzalez ◽  
Marcos Perez Gonzalez ◽  
Frank Scholl ◽  
Steven Bibevski ◽  
Elena Ladich ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Valve Replacement ◽  
De Novo ◽  
Primate Model ◽  
Time Points ◽  
Baboon Model ◽  
Additional Processing ◽  
Porcine Small Intestinal Submucosa ◽  
Intestinal Submucosa

The utility of implanting a bioscaffold mitral valve consisting of porcine small intestinal submucosa (PSIS) in a juvenile baboon model (12 to 14 months old at the time of implant; n = 3) to assess their in vivo tissue remodeling responses was investigated. Our findings demonstrated that the PSIS mitral valve exhibited the robust presence of de novo extracellular matrix (ECM) at all explantation time points (at 3-, 11-, and 20-months). Apart from a significantly lower level of proteoglycans in the implanted valve’s annulus region (p < 0.05) at 3 months compared to the 11- and 20-month explants, there were no other significant differences (p > 0.05) found between any of the other principal valve ECM components (collagen and elastin) at the leaflet, annulus, or chordae tendinea locations, across these time points. In particular, neochordae tissue had formed, which seamlessly integrated with the native papillary muscles. However, additional processing will be required to trigger accelerated, uniform and complete valve ECM formation in the recipient. Regardless of the specific processing done to the bioscaffold valve, in this proof-of-concept study, we estimate that a 3-month window following bioscaffold valve replacement is the timeline in which complete regeneration of the valve and integration with the host needs to occur.

Abstract 14888: Extracellular Matrix Quantification of Fully Regenerated Neochorade After Bio-scaffold Mitral Valve Implantation in a Juvenile Non-human Primate Model

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Brittany A Gonzalez ◽  
Marcos Gonzalez Perez ◽  
Asad Mirza ◽  
Frank Scholl ◽  
Steven Bibevski ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Mitral Valve ◽  
Oscillatory Flow ◽  
Treatment Options ◽  
Left Ventricular ◽  
Primate Model ◽  
Cardiac Tissues ◽  
Mitral Valves ◽  
Intestinal Submucosa ◽  
Post Implantation

Introduction: To investigate enhanced treatment options for critical mitral valve disease in children, we implanted a bio-scaffold mitral valve comprising of porcine small intestinal submucosa (PSIS) in a juvenile baboon model. Hypothesis: New tissue formation would be accelerated at physical connections between the replacement bio-scaffold valve and native cardiac tissues, due to direct extracellular matrix (ECM) communications. Methods: Juvenile baboons (n=2) were implanted with a hand-made bicuspid PSIS (Cormatrix, Roswell, GA) mitral valve. The PSIS valves were excised at 11- and 20-months post-implantation. Images of histological stains (Movat’s Pentachrome; Alizée Pathology, Inc., Thurmont, MD) were subsequently spatially mapped for ECM quantification (MATLAB; Mathworks, Natick, MA). Results: PSIS bio-scaffold mitral valves (11- and 20-months post-implantation) facilitated complete regeneration of neochordae. The neochordae seamlessly integrated into the papillary muscles and left ventricular insertion sites ( Figure 1A, E ). We also found that with an increase in implantation duration of ~ 9 months, the collagen, proteoglycan and elastin content (per mm 2 ; Figure 1B-D, F-H ) had a fold-change of 6.96, 18.42 and 4.94, respectively. Conclusions: Our findings suggest that the PSIS bio-scaffold mitral valve apparatus can regenerate neochordae without the need for any biochemical or biomechanical treatment. Nonetheless, other valve spatial areas of importance (e.g. leaflets) will require additional strategies. As a next step, we will produce oscillatory flow-conditioned, stem cell-derived ECM, to accelerate tissue regeneration. The mechanical parameters that we computed to permit physiological oscillatory flow conditions are an oscillatory shear index (OSI) of 0.23 and time averaged bio-scaffold shear stress (TAB-SSS) of 4.6 dynes/cm 2 . Acknowledgements: AHA Award ID: 16GRNT31090009; The Miami Research Heart Institute; FIU-UGS DYF.

scholarly journals Septic cardiomyopathy: evidence for a reduced force-generating capacity of human atrial myocardium in acute infective endocarditis

2017 ◽  
Vol 2 (2) ◽  
pp. 81-87 ◽  
Author(s):  
Katja Buschmann ◽  
Ryan Chaban ◽  
Anna Lena Emrich ◽  
Marwan Youssef ◽  
Angela Kornberger ◽  
...  
Keyword(s):  
Infective Endocarditis ◽  
Mitral Valve ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Isometric Force ◽  
Active Force ◽  
Atrial Myocardium ◽  
Force Amplitude ◽  
Generating Capacity

AbstractBackground:This study analyzes the myocardial force-generating capacity in infective endocarditis (IE) using an experimental model of isolated human atrial myocardium. In vivo, it is difficult to decide whether or not alterations in myocardial contractile behavior are due to secondary effects associated with infection such as an altered heart rate, alterations of preload and afterload resulting from valvular defects, and altered humoral processes. Our in vitro model using isolated human myocardium, in contrast, guarantees exactly defined experimental conditions with respect to preload, afterload, and contraction frequency, thus not only preventing confounding by in vivo determinants of contractility but also excluding effects of other factors associated with sepsis, hemodynamics, humoral influences, temperature, and medical treatment.Methods:We analyzed right atrial trabeculae (diameter 0.3–0.5 mm, initial length 5 mm) from 32 patients undergoing aortic and/or mitral valve replacement for acute valve incompetence caused by IE and 65 controls receiving aortic and/or mitral valve replacement for nonendocarditic valve incompetence. Isometric force amplitudes and passive resting force values measured at optimal length in the two groups were compared using Student’s t-test.Results:There were no significant differences between the groups in terms of the passive resting force. The isometric force amplitude in the endocarditis group, however, was significantly lower than in the nonendocarditis group (p=0.001). In the endocarditis group, the calculated active force, defined as the isometric force amplitude minus the resting force, was significantly lower (p<0.0001) and the resting force/active force ratio was significantly higher (p<0.0001). Using linear regression to describe the function between resting force and active force, we identified a significant difference in slope (p<0.0001), with lower values found in the endocarditis group.Conclusion:Our data suggest that the force-generating capacity of atrial myocardium is significantly reduced in patients with IE. In these patients, an elevated resting force is required to achieve a given force amplitude. It remains unclear, however, whether this is due to calcium desensitization of the contractile apparatus, presence of myocardial edema, fibrotic remodeling, disruption of contractile units, or other mechanisms.

scholarly journals Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 639-642 ◽  
Author(s):  
A Gruber ◽  
JH Griffin ◽  
LA Harker ◽  
SR Hanson
Keyword(s):  
Protein C ◽  
Thrombus Formation ◽  
Activated Protein C ◽  
Graft Patency ◽  
Scintillation Camera ◽  
Primate Model ◽  
Baboon Model ◽  
Platelet Deposition ◽  
Antithrombotic Effects

The in vivo antithrombotic properties of human plasma activated protein C (APC), a natural anticoagulant enzyme, were investigated in a baboon model of thrombus formation on prosthetic vascular grafts. Infusion of 0.25 to 1.1 mg/kg/h purified, human, APC inhibited blood clotting, as measured by the activated partial thromboplastin time (APTT), and reduced vascular graft platelet deposition by 40% to 70%, as determined by the real-time scintillation camera imaging of 111In-labeled platelet deposition. APC infusion also preserved graft patency. Hemostatic plug formation remained normal, as measured by the template bleeding times. These results suggest that APC administration may produce immediate antithrombotic effects under arterial flow conditions.

scholarly journals EVEREST II randomized clinical trial: Predictors of mitral valve replacement in de novo surgery or after the MitraClip procedure

2012 ◽  
Vol 143 (4) ◽  
pp. S60-S63 ◽  
Author(s):  
Donald Glower ◽  
Gorav Ailawadi ◽  
Michael Argenziano ◽  
Michael Mack ◽  
Alfredo Trento ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mitral Valve ◽  
Randomized Clinical Trial ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
De Novo

Porcine Small Intestinal Submucosa Mitral Valve Material Responses Support Acute Somatic Growth

2020 ◽  
Vol 26 (9-10) ◽  
pp. 475-489 ◽  
Author(s):  
Brittany A. Gonzalez ◽  
Elnaz Pour Issa ◽  
Omkar V. Mankame ◽  
Jenniffer Bustillos ◽  
Antonio Cuellar ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Somatic Growth ◽  
Small Intestinal Submucosa ◽  
Porcine Small Intestinal Submucosa ◽  
Small Intestinal ◽  
Intestinal Submucosa

Ex-vivo and In-vivo Validation of Novel Quantitative Videodensitometric Assessment of Mitral Regurgitation Following Surgical Mitral Valve Replacement

2021 ◽  
Vol 5 (sup1) ◽  
pp. 58-58
Author(s):  
Patrick Serruys ◽  
Hideyuki Kawashima ◽  
Masafumi Ono ◽  
Jean-Paul Aben ◽  
Michele Pighi ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Regurgitation ◽  
Valve Replacement ◽  
Mitral Valve Replacement ◽  
Ex Vivo ◽  
In Vivo Validation

An in vivo study of the host tissue response to subcutaneous implantation of PLGA- and/or porcine small intestinal submucosa-based scaffolds

Biomaterials ◽  
2007 ◽  
Vol 28 (34) ◽  
pp. 5137-5143 ◽  
Author(s):  
Moon Suk Kim ◽  
Hyun Hee Ahn ◽  
Yu Na Shin ◽  
Mi Hee Cho ◽  
Gilson Khang ◽  
...  
Keyword(s):  
Small Intestinal Submucosa ◽  
Host Tissue ◽  
Tissue Response ◽  
In Vivo Study ◽  
Subcutaneous Implantation ◽  
Porcine Small Intestinal Submucosa ◽  
Small Intestinal ◽  
Intestinal Submucosa

scholarly journals Inhibition of platelet-dependent thrombus formation by human activated protein C in a primate model

Blood ◽  
1989 ◽  
Vol 73 (3) ◽  
pp. 639-642 ◽  
Author(s):  
A Gruber ◽  
JH Griffin ◽  
LA Harker ◽  
SR Hanson
Keyword(s):  
Protein C ◽  
Thrombus Formation ◽  
Activated Protein C ◽  
Graft Patency ◽  
Scintillation Camera ◽  
Primate Model ◽  
Baboon Model ◽  
Platelet Deposition ◽  
Antithrombotic Effects

Abstract The in vivo antithrombotic properties of human plasma activated protein C (APC), a natural anticoagulant enzyme, were investigated in a baboon model of thrombus formation on prosthetic vascular grafts. Infusion of 0.25 to 1.1 mg/kg/h purified, human, APC inhibited blood clotting, as measured by the activated partial thromboplastin time (APTT), and reduced vascular graft platelet deposition by 40% to 70%, as determined by the real-time scintillation camera imaging of 111In-labeled platelet deposition. APC infusion also preserved graft patency. Hemostatic plug formation remained normal, as measured by the template bleeding times. These results suggest that APC administration may produce immediate antithrombotic effects under arterial flow conditions.

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