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Biomedical subjects

Michael Scharfschwerdt

Publications and source records attributed to Michael Scharfschwerdt.

7 recordsLinked to original sources

Mitochondrial DNA deletions and the aging heart.

Mitochondrial DNA (mtDNA) mutations appear to be associated with a wide spectrum of human disorders and proposed to be a potential contributor of aging. However, in an age-dependent increase of the common 4977 bp deletion of human mtDNA still many unanswered questions remain. Comparing mtDNA copy levels in different tissues revealed that cardiac muscle had the highest, while the cortex cerebelli showed the lowest copy number of mtDNA in every donor. Intriguingly, mtDNA copy number showed no changes during aging. In heart tissue, the amount of 4977 bp mtDNA deletion increased in an age-dependent manner showing significant differences at the age of 40 years and older (p<0.005). In vitro studies analyzing human normal cells transfected with telomerase (BJ-T) revealed that oxidative stress (OS)--a well accepted promoter of aging--induced 4977 bp deletion and point mutations as demonstrated by real-time PCR and DHPLC analysis. Interestingly, OS induced apoptosis only in transformed human fibroblasts by activation of the intrinsic (mitochondrial-mediated) signalling pathway as indicated by morphological damage of mitochondria, DNA laddering and increase of the Bax/Bcl-2 ratio. In conclusion, in heart tissue, the amount of the 4977 bp deletion increased in an age-dependent manner and it was more detectable after the 4th decade of life, although there was some scatter in the data. Since, apoptosis was induced by the mitochondria-mediated pathway only in transformed cells, the role for apoptosis in normal tissue of the aging heart remains unclear.

Adolescent↗

In-vitro study on the relationship between progressive sinotubular junction dilatation and aortic regurgitation for several stentless aortic valve substitutes.

OBJECTIVE: Stentless aortic valves are widely used due to their excellent hemodynamic properties. However, if the subcoronary implantation technique is used later dilatation of the sinotubular junction (STJ) can cause regurgitation. The aim of the study was to determine the dilatation tolerance of two commercially available stentless xenografts and fresh aortic and pulmonary roots against such dilatation. METHODS: Four groups each comprising five specimens of fresh porcine aortic roots, pulmonary roots, Medtronic freestyle or Toronto SPV Xenografts were tested in a mock circulation using a special device for gradually increasing the diameter of the sinotubular junction. The smallest diameter D(r) where regurgitation occurs was measured and correlated with the starting diameter D(a) and expressed as per cent values. Opening and closing patterns were obtained by a high speed camera and flow characteristics were determined. RESULTS: The highest dilatation tolerance of STJ was found in the fresh porcine aortic roots (165%+/-10) followed by fresh pulmonary roots (146%+/-12), the Freestyle (143%+/-4) and the SPV (132%+/-5) bioprostheses. All differences were significant with P< or =0.05 except that between the fresh pulmonary roots and the two commercial available bioprostheses. CONCLUSIONS: Our results indicate that aortic homografts provide higher resistance against regurgitation induced by dilatation of the STJ than an autograft or the stentless xenografts, Freestyle xenograft followed by the Toronto SPV. The use of the full-root technique should be considered if aortic dilatation seems to be likely.

Aortic Valve↗

In vitro hydrodynamics, cusp-bending deformation, and root distensibility for different types of aortic valve-sparing operations: remodeling, sinus prosthesis, and reimplantation.

OBJECTIVE: Preserving aortic valve cusps during operations for aortic root pathology theoretically offers several advantages over alternative prosthetic valve-bearing conduits. Functional properties of different valve-sparing techniques under defined conditions are not well studied. METHODS: Fresh porcine aortic roots were investigated in a pulsatile flow simulator, either native root or after different types of valve-sparing procedures (remodeling, sinus prosthesis, and reimplantation). Functional parameters, such as transvalvular pressure gradient, closing volume, cusp-bending deformation, and distensibility at different levels of the root were analyzed. RESULTS: The mean pressure gradient was highest in reimplantation techniques (8.4 +/- 1.8 mm Hg) compared with sinus prostheses (7.2 +/- 0.9 mm Hg, P = .01) and remodeling techniques (6.8 +/- 1.0 mm Hg, P = .002), mirror imaging the closing volume (reimplantation, 1.5 +/- 0.4 mL; sinus prostheses, 2.3 +/- 0.7 mL [P < .001]; remodeling, 3.4 +/- 1.1 mL [P < .001]). Bending deformation indices increased significantly from remodeling (0.45 +/- 0.05) and sinus prostheses (0.58 +/- 0.06) to reimplantation techniques (0.73 +/- 0.09). Dynamic changes in area of all techniques were decreased at the sinotubular junction and the commissural and sinus levels when compared with those seen in native roots but increased at the annular level for techniques with unfixed annulus (remodeling and modified sinus prosthesis). CONCLUSIONS: In vitro the various aortic valve-sparing operations differed characteristically in their ability to spare valve function, none of them completely meeting native valve behavior. The remodeling techniques exhibited valve dynamics closest to those of the native aortic root. The more the aortic valve is fixed with noncompliant prosthetic material, the more the native root dynamics are impaired.

Animals↗

A novel, form-stable, anatomically curved vascular prosthesis for replacement of the thoracic aorta.

PURPOSE: Current replacement of the thoracic aorta performed with straight vascular prostheses may cause kinking, potentially affecting hemodynamics and promoting vortices and thrombus formation. A novel vascular prosthesis, resistant to pressure-related shape deformation, was designed to imitate the curved anatomy of the thoracic aorta. DESCRIPTION: A woven velour prosthesis was trimmed with cross-sutures along a marked line, resulting in a curved-shaped anatomic form, and was compared with conventional straight and thermally fixed curved grafts. The vascular prostheses were fixed at both ends at various base distances (8, 10, 12, 14, and 16 cm) and pressurized. To imitate the neck vessels an abutment was fixed at the upper convexity of the grafts. Radius of curvature or depth of kinking was measured at different pressures (100, 125, and 150 mm Hg). Pressure gradients and flow profiles were further analyzed in an aortic arch glass model. EVALUATION: When pressurized the straight and the thermally fixed protheses showed double kinking before and behind the abutment at all pressures and distances. Kinking depth increased with increasing pressure and less base distance. Transkinking pressure gradients increased with the degree of kinking. In a glass model flow profiles showed postkinking turbulences and vortex formation. The newly designed vascular prosthesis showed no kinking and remained form stable at all test conditions. CONCLUSIONS: This novel curved vascular prosthesis for replacement of the thoracic aorta demonstrates form stability compared with conventional straight and thermally fixed vascular prostheses in an aortic arch model, with smaller pressure gradients and flow disturbances.

Aorta, Thoracic↗

Mechanical and structural properties of a novel hybrid heart valve scaffold for tissue engineering.

Hybrid heart valve scaffolds were fabricated from decellularized porcine aortic heart valve matrices and enhanced with bioresorbable polymers using different protocols: (i) dip coating of lyophilized decellularized matrices, and (ii) impregnation of wet decellularized matrices. The following polymers were evaluated: poly(4-hydroxybutyrate) and poly(3-hydroxybutyrate-co4-hydroxybutyrate). Tensile tests were conducted to assess the biomechanical behavior of valve leaflet strips. Suture retention strength was evaluated for the adjacent conduit. A pulse duplicator system was used for functional testing of the valves under physiological systemic load conditions. The properties of the hybrid structures were compared with native, decellularized, and glutaraldehyde-fixed specimens. Mechanisms of the polymer impregnation process were studied with IR spectroscopy, fluorescent microscopic imaging, and SEM. Altogether this study demonstrates the feasibility and improved biomechanical function of a novel hybrid heart valve scaffold for an application in tissue engineering.

Animals↗

Improved hydrodynamics of a new aortic cannula with a novel tip design.

BACKGROUND: Reduction of atheroembolic complications during cardiopulmonary bypass remains a major challenge in cardiac surgery. New cannula tip designs may help to attenuate this problem by improved hydrodynamics. METHODS: Pressure gradients and back pressures of a new aortic cannula tip design were measured and compared with the Medos X-Flow, Sarns Soft-Flow and Argyle THI cannulae at various flow rates in a mock circulation followed by flow visualization. RESULTS: Pressure gradients were the lowest for the new cannula. Back pressures of the new cannula were up to 84% lower than for the Argyle cannula. The back pressure profile and flow visualization of the new cannula showed broad centric flow dispersion with a transcannula increase of flow area from 38 mm2 to 139 mm2. CONCLUSIONS: The new design of an aortic cannula tip provides improved hydrodynamics, with low pressure gradients, low back pressures and a uniform central dispersion of flow, reducing the sandblasting effect.

Aorta↗

The influence of a nonlinear resistance element upon in vitro aortic pressure tracings and aortic valve motions.

In vitro testing of biological heart valves requires pressure and flow waveforms closely simulating natural conditions, which are mainly influenced by the characteristics of the vascular system. Simulation of the arterial function in artificial circulations was mostly performed by the useful Windkessel model but sometimes failed by generating inadequate systolic pressures. The integration of a novel nonlinear resistance element may improve the Windkessel function. Native porcine aortic valves were studied in a mock circulation with a novel nonlinear resistance element combined with the Windkessel compared with an aperture plate resistance. Pressure and flow measurements were performed at varying heart rates and stroke volumes and analyzed in the time and frequency domain. Aortic valve motions were evaluated using high speed video recording. With the classical afterload configuration including an aperture plate resistance, the pressure tracings showed a nonphysiologic decrease of pressure during systole after early peak pressure. By integration of the novel nonlinear resistance, peak systolic pressure occured later, peak pressure was higher, and the pressure waveform was more physiologically shaped. Leaflet motions of the aortic valves were less oscillatory and compared well with in vivo characteristics. In conclusion, a novel nonlinear resistance element in a mock circulation has the potential to provide more physiologic aortic pressure waveforms as influencing aortic valve dynamics and thus may be a helpful tool for investigation of biological heart valves.

Animals↗