S-Space College of Medicine/School of Medicine (의과대학/대학원) Dept. of Medicine (의학과) Theses (Ph.D. / Sc.D._의학과)
Perventricular pulmonic valve implantation using xenograft valves mounted on self-expandable stent
자가 확장식 스텐트에 장착된 이종 판막을 이용한 경심실 폐동맥 판막 치환술 :
- 의과대학 의학과
- Issue Date
- 서울대학교 대학원
- 학위논문 (박사)-- 서울대학교 대학원 : 의학과 흉부외과학 전공, 2016. 8. 김용진.
- Background: The aims of this study were (1) to compare the hemodynamics, durability, and degenerative changes between the two different xenogenic valves (porcine pericardial versus aortic valve xenografts) implanted into the pulmonary valve position using a perventricular implantation technique in sheep, and (2) to evaluate the safety and efficacy of perventricular implantation of stented pulmonic valve as a preclinical study.
Materials and Methods: Porcine pericardial and aortic valve tissues were treated by our tissue treatment technique in order to improve durability
they were decellularized, alpha-galactosidase treated, treated with space-fillers and glutaraldehyde, and detoxified. A xenograft valve made of porcine pericardial or aortic valve tissue was manufactured as a stented valve mounted on Nitinol wire that has shape-memory and self-expanding properties. The stented porcine pericardial and aortic valves were implanted into the pulmonary valve position using a perventricular implantation technique under echocardiographic and angiographic guidance in 18 sheep (group PP, pericardial xenograft implantation, n=9
group PAV, aortic valve xenograft implantation, n=9). Hemodynamic and immunohistochemical studies were performed after the implantation, and radiologic, histologic, and calcium quantification studies were performed after a terminal procedure.
Results: All stented valves were positioned properly so a low-pressure gradient between the right ventricle and pulmonary artery was seen immediately after the implantation (median peak pressure gradient: groups PP versus PAV, 4.0 mmHg versus 5.0 mmHg). Of 18 animals, 8 (group PP, n=5
group PAV, n=3) survived more than 300 days. Median survivals of animals were 352 days [87 days, 402 days] and 173 days [98 days, 376 days] in groups PP and PAV, respectively. Echocardiographic and cardiac catheterization studies were performed prior to a scheduled terminal procedure (median follow-up duration 437 days [389 days, 504 days]) In 7 of 8 animals (group PP, n=4
group PAV, n=3). Good hemodynamic state and function of the bioprosthetic valve were demonstrated in all 7 animals. None of the animals showed significant pulmonary regurgitation or stenosis, demonstrating a low-pressure gradient between right ventricle and pulmonary artery (median peak pressure gradient
groups PP vs. PAV, 5.0 mmHg versus 6.0 mmHg). All the anti-α-Gal IgM and IgG titers measured by enzyme-linked immunosorbent assay were below 0.3 OD and median calcium contents were 0.95μg/mg [0.67μg/mg, 1.13μg/mg] and 2.13 μg/mg [1.18μg/mg, 2.6μg/mg] in groups PP and PAV, respectively. Gross examination of extracted valves showed no calcification or RVOT obstructions, and microscopic findings revealed a minimal amount of calcification in both groups. Regardless of the implantation duration, no significant infiltration of macrophage or T-cell was observed in both groups, by immunofluorescence study. Computed tomography study of the extracted valves performed in 11 animals (group PP, n=4
group PAV, n=7) showed no significant differences between the 2 groups (p = 0.927). The quantity of calcifications analyzed using hydrolysate showed higher calcium contents in group PP tissues than in group PAV tissues (group PP, n=9, 2.13μg/mg [1.18μg/mg, 2.6μg/mg]
group PAV, n=9, 0.95μg/mg [0.67μg/mg, 1.13μg/mg]
p = 0.019).
Conclusion: Perventricular pulmonic valve implantation is a feasible technique, which has a high success rate and produces a good hemodynamic profile. The tissue treatment technique of glutaraldehyde fixation with simultaneous use of multiple anti-calcification methods, including decellularization, immunological modification with α-galactosidase, space-filler treatment, organic solvent treatment, and detoxification, was shown to be an applicable method in treatment of bioprostheses. Both stented valves made of porcine pericardial and aortic valve tissues showed no significant differences in hemodynamic profile, midterm durability and degree of degenerative dystrophic calcification.