• Journal of Chest Surgery
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• 제22권6호
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• pp.1001-1012
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• 1989

In 1968, Carpentier and his associates introduced glutaraldehyde as a compound for preparing cardiac tissue valve, and this technique has provided a considerably more suitable and durable tissue valve substitute. To increase further durability of valve tissue, Reis and his colleagues designed a flexible stent to reduce the stress on the heterogeneous tissue valve mounted. However with the advent of more innovative mechanical valve currently, many bioprosthetic valves are being substituted by mechanical valves at our department of cardiothoracic surgery because of bioprosthetic valve failure. Main cause of bioprosthetic valves failure were calcification or/and tear of tissue valves. The purpose of this retrospective study is to clarify the relationship between the patients clinical profile during implantation of tissue valves and pathologic features of the failed bioprosthetic valve. From March, 1982 through June, 1988, 53 bioprosthetic heart valves that had been ex-planted from 45 patients at the department of cardiac surgery of Yonsei University Hospital were subjected to this study. The patients were 10 to 65 year-old [mean age: 30.3 yr] with 17 males and 28 females. Re-replacements of prosthetic valves were carried out twenty nine in mitral position, eight in aortic position and eight in both aortic and mitral position simultaneously. The grading and location for calcification of valves were verified by radiograms. The calcification of the explanted valves leaflets was graded from 0 to 4 plus according to Cipriano and associates method. The types of tear and perforation of leaflet were classified into four types as Ishihara has adopted initially in 1981. In younger age group under thirty three years, explanted tissue valves were significantly more affected in terms of grades of severity of valve calcification as compared with older age group [p < 0.035]. Valve calcification appeared more severe in male as compared to female [p< 0.002]. Ionescu-Shiley bovine pericardial bioprosthetic valves showed more severe calcification than Hancock porcine tissue valves [p< 0.035]. Calcium deposit was found very prevalent at the area of commissural attachment [86 % of all]. Type I of valve rupture was shown to be related with simultaneous calcification. However, the relation of explanted valve position, duration of implanted prosthetic valve, atrial fibrillation and anticoagulant therapy to the severity of bioprosthetic valve calcification were not significantly clear statistically [p > 0.05].

• Journal of Chest Surgery
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• 제26권9호
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• pp.667-676
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• 1993

Boprosthetic cardiac valves fail from biological and metabolic as well as mechanical reasons, and the limited durability is the main factor of marked withdrawal in their clinical use. Starting the use of bioprosthetic valves in 1976, up to the end of 1992, the consecutive 178 patients have undergone re-replacement of glutaraldehyde-treated xenograft valves for primary tissue failure [PTF]among the patients who had initial valve replacement at Seoul national University Hospital. The explanted valves were 69 porcine aortic [51 Hancock, 12 Angell-Shiley and 6 Carentier-Edwards] and 141 bovine pericardial [129 standard-profile and 12 low-profile ionescu-Shiley] valwes, with an overall incidence of PTF of 15.2%. The operative mortality rate of re-replacement was 5.1%. Calcific degeneration and tissue damage in relation to calcification were the most frequent modes of PTF on gross examinatin of the explanted valves resulting hemodynamically in valvular regurgitation. The number of Hancocg porcine and the standard-profile Ionescu-Shiley valves in valves in mitral position failed more often from tissue damage [tears, holes, and loss or destruction of cuspal tissue] than calcification [68.3% vs. 39.0%, p<0.01] with resultant regurgitation in 61%, the Ionescu-Shiley valves in the same position in 53%. The tendency of more calcification than tissue damage[71.3% vs. 33.3%, p<0.001]with stenosis in 53%. The tendency of more calcification and immobility of cusps in the latter group was partly explainable by the inclusion of patients of pediatric age. Observation made in this study suggest : many of bioprosthetic valves would fail from calcification and tissue damage : some fail prematurely because of mechanical stress probably owing to the valve design in construction ; andeven those valves escaped early damage would be subject to calcify in the prolonged follow-up period. In conclusion, at the present time, the clinical use of bioprostheticxenograft valves seems to be quite limited until further improvement in biocompatibility and refinement in valve design in manufacture are achieved.

• Korean Circulation Journal
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• 제54권1호
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• pp.57-58
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• 2024

• Journal of Chest Surgery
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• 제44권2호
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• pp.99-107
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• 2011

Background: Calcification is the most frequent cause of clinical failure of bioprosthetic tissues fabricated from GA-fixed porcine valves or bovine pericardium. A multi-factorial approach using different mechanisms was recently developed to reduce the calcification of bioprosthetic tissues. The purpose of the present study was to evaluate the synchronized synergism of using L-arginine and $NaBH_4$, compared with ethanol and L-lysine, in glutaraldehyde treated porcine pericardium from the standpoint of calcification and tissue elasticity. Materials and Methods: Porcine pericardium was fixed at 0.625% GA (7 days at room temperature after 2 days at $4^{\circ}C$). An interim step of ethanol (80%; 1 day at room temperature) or L-lysine (0.1 M; 2 days at $37^{\circ}C$) or L-arginine (0.1 M; 2 days at $37^{\circ}C$) was followed by completion of the GA fixation. A final step of NaBH4 (0.1 M; 2 days at room temperature) was followed. Their tensile strength, thickness, and thermal stability were measured. Treated pericardia were implanted subcutaneously into three-week-old Sprague-Dawley rats for 8 weeks. Calcium content was assessed by atomic absorption spectroscopy and histology. Results: L-arginine and $NaBH_4$ pretreatment ($1.81{\pm}0.39$ kgf/5 mm p=0.001, $0.30{\pm}0.08$ mm p<0.001) significantly increased tensile strength and thickness compared with the control ($0.53{\pm}0.34$ kgf/5 mm, $0.10{\pm}0.02$ mm). In a thermal stability test, L-arginine and $NaBH_4$ pretreatment ($84.25{\pm}1.12^{\circ}C$, p=0.023) caused a significant difference from the control ($86.25{\pm}0.00^{\circ}C$). L-lysine and $NaBH_4$ pretreatment ($183.8{\pm}42.6$ ug/mg, p=0.804), and L-arginine and $NaBH_4$ pretreatment ($163.3{\pm}27.5$ ug/mg, p=0.621) did not significantly inhibit calcification compared to the control ($175.5{\pm}45.3$ ug/mg), but ethanol and $NaBH_4$ pretreatment did ($38.5{\pm}37.3$ ug/mg, p=0.003). Conclusion: The combined pretreatment using L-arginine and $NaBH_4$ after GA fixation seemed to increase the tensile strength and thickness of porcine pericardium, fixed with GA. Additionally, it seemed to keep thermal stability. However it could not decrease the calcification of porcine pericardium fixed with GA. $NaBH_4$ pretreatment seemed to decrease the calcification of porcine pericardium fixed with GA, but only with ethanol.

• Biotechnology and Bioprocess Engineering:BBE
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• 제10권3호
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• pp.218-224
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• 2005

Surface modification of glutaraldehyde fixed bovine pericardium (GFBP) was success­fully carried out with hyaluronic acid (HA) derivatives. At first, HA was chemically modified with adipic dihydrazide (ADH) to introduce hydrazide functional group into the carboxyl group of HA backbone. Then, GFBP was surface modified by grafting HA-ADH to the free aldehyde groups on the tissue and the subsequent HA-ADH hydrogel coating. HA-ADH hydrogels could be prepared through selective crosslinking at low pH between hydrazide groups of HA-ADH and crosslinkers containing succinimmidyl moieties with minimized protein denaturation. When HA­ADH hydrogels were prepared at low pH of 4.8 in the presence of erythropoietin (EPO) as a model protein, EPO release was continued up to $85\%$ of total amount of loaded EPO for 4 days. To the contrary, only $30\%$ of EPO was released from HA-ADH hydrogels prepared at pH=7.4, which might be due to the denaturation of EPO during the crosslinking reaction. Because the carboxyl groups on the glucuronic acid residues are recognition sites for HA degradation by hyaluronidase, the HA-ADH hydrogels degraded more slowly than HA hydrogels prepared by the crosslinking reaction of divinyl sulfone with hydroxyl groups of HA. Following a two-week subcutaneous implantation in osteopontin-null mice, clinically significant levels of calcification were observed for the positive controls without any surface modification. However, the calcification of surface modified GFBP with HA-ADH and HA-ADH hydrogels was drastically reduced by more than $85\%$ of the positive controls. The anti-calcification effect of HA surface modification was also confirmed by microscopic analysis of explanted tissue after staining with Alizarin Red S for calcium, which followed the trend as observed with calcium quantification.

• Journal of Chest Surgery
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• 제24권9호
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• pp.837-842
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• 1991

Calcification is a major problem in glutaraldehyde-preserved bioprosthetic valves. We have used bovine pericardium processed in a solution containing 0.625% glutaraldehyde, 0.05M HEPES buffer and 0.26% magnesium chloride in saline. And, we also treated the glutaraldehyde-preserved bovine pericardium with a surfactant, Triton X - 100 to reduce calcification. To evaluate the degree of calcification. 4 kinds of pericardial xenografts, group I [Xenomedica, equine pericardial xenografts], group II [0.625% glutaraldehyde-preserved bovine pericardiums], group III [0.5% Triton X - 100 treated bovine pericardiums], and group IV [1.2% Triton X - 100 treated bovine pericardiums] were implanted in subcutaneous layer of growing rabbits, and they were explanted about 3 months later. The mean calcium contents[%/mg of dry tissue] of 0.5% and 1.2% Triton X - 100 treated bovine pericardiums [80.0$\pm$27.1%: 78.6$\pm$47.0% respectively] were lower than those of glutaraldehyde-preserved bovine pericardiums[126.2$\pm$29.8] [p=0.05]. Thus, under the conditions of subcutaneous implantation in rabbits, Triton X - 100 was efficient in calcification mitigation.

• Journal of Chest Surgery
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• 제29권10호
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• pp.1111-1117
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• 1996

표준형 이오네스큐우심낭판막의 일차성 조직실패상의 특징의 일부를 알아보고져 승모판위치에서 각 각 행콕판막을 적출하였던 56례와 표준형 이오네스큐판막을 적출하였던 연속적 전례인 일차성 조직실 패환자 113례를 대상으로 임상 및 병리학적으로 분석 검토하였다. 양 환자군의 수술당시의 연령은 각각 31.9$\pm$9.2세와 30.4$\pm$ 12.5세였다. 행콕판막은 조직손상으로 인 한 판막폐쇄부전이 빈발한 반면 이오네스큐판막은 석회화변성의 빈도가 높고 협착병변인 경향이 우세 하였다. 판막적출기간은 행콕판막에서보다 이오네스큐판막에서 단축되 었다. 이러한 판막실패의 특징은 판막구조설계의 개선으로 기계적 요소로 인한 판막실패를 감소할 수 있을 것으로 보이나 항광물화상의 개선 없이는 조직판막의 내구성의 개선은 곤난할 것임을 시사하였다.

• Korean Circulation Journal
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• 제54권1호
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• pp.43-56
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• 2024

Background and Objectives: The therapeutic strategy for inflammation and degenerative calcification is of utmost importance for bioprosthetic heart valve (BHV) implanted patients. The purpose of this study was to compare the anti-inflammatory and anti-calcification effects of Entelon150^® (grape seed extract), losartan, and rosuvastatin, in a rabbit model of intravascular BHV leaflet implantation in bovine pericardium. Methods: A total of 28 rabbits were implanted with BHV leaflet in the external jugular veins. The Entelon150^® group was administered 7.7 mg/kg Entelon150^® twice daily for 6 weeks after surgery. The losartan and rosuvastatin groups received 5.14 mg/kg and 1 mg/kg, respectively, once per day. The control group received 1 ml of saline once daily. And then, calcium concentration was measured in the implanted BHV, and histological and molecular analyses were performed on the surrounding tissues. Results: The calcium content of the implanted tissue in the Entelon150^® group (0.013±0.004 mg/g) was lower than that in the control group (0.066±0.039 mg/g) (p=0.008). The losartan (0.024±0.016 mg/g, p=0.032) and rosuvastatin (0.022±0.011 mg/g, p=0.032) groups had lower calcium content than the control group, and higher tendency than the Entelon150^® group. Immunohistochemistry revealed that the expressions of bone morphogenic protein 2 (BMP2), S-100, and angiotensin II type 1 receptor in the Entelon150^® group showed lower tendency than those in the control group. The protein expression levels of BMP2 were reduced in the Entelon150^® group compared with those in the control group. Conclusions: Entelon150^® exhibited a significant effect, similar to other drugs, in reducing calcification and inflammation in the intravascular bovine pericardium.

• Journal of Chest Surgery
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• 제31권11호
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• pp.1023-1030
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• 1998

연구배경 : 인체내 이식된 생체조직들은 석회화 변성으로 인해 그 내구성이 단축된다. 이러한 조직들을 이식하기전에 글루타르알데하이드(GA)로 고정후 sulphonated polyethyleneoxide(PEO-SO3)를 결합시키고 또한 조직내 의 잔유 알데히드기를 제거함으로써 석회화에 대한 내구성을 향상시킬 수 있다 재료 및 방법 : PEO-SO3 처리법과 잔유 알데히드기 제거의 석회화 방지 효과를 알아보기 위하여 GA 고정 후 PEO-SO3로 처리한 소 심낭 첨포를 잔유 알데히드기 제거를 위해 무균 생리식염수에 보존한 saline 군과 0.65% GA 용액 에 보존한 GA군, 그리고 이미 상품화되어 임상에서 사용되고 있는 product군을 8마리 개의 경동맥과 대퇴동 맥 및 복막에 이식하여 6주 후 적출하여 칼슘량 및 병리조직 소견에 대해 알아보았다. 결과 : 경동맥에서 채취한 조직첨포의 칼슘량은 saline군에서 GA군과 product군에 비해 유의하게 적었다 (saline; 2.89$\pm$0.31 vs. GA; 6.14$\pm$1.08 vs. product; 22.82$\pm$5.00 mg/g; p< .05). 대퇴동맥과 복막 이식 첨포에서의 칼슘량 또한 saline군에서 다른 두 군에 비해 가장 적었으나 통계적인 유의성은 없었다. 한편 병리조직 검사에서는 GA군에서 다른 두 군에 비해 조직의 석회화로 인한 변성 파괴가 심하였다. 결론 : 본 연구에서 소 심낭 조직 첨포와 결합한 PEO-SO3는 석회화를 감소시키고 또한 조직내 잔유 알데히드기 를 생리식염수로 세척하여 제거함으로써 항석회화 효과를 증가시킬 수 있었다. 결론적으로 PEO-SO3로 처리한 소 심낭 조직은 석회화 변성에 대한 강한 저항성을 보임으로써 심혈관 첨포나 인공 조직 판막 개발 에 도움를 줄 수 있을 것이다.

• Journal of Chest Surgery
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• 제42권6호
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• pp.685-695
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• 2009

배경: 이종조직의 석회화는 기존에 사용된 돼지 판막이나 소 심낭을 이용한 생체 인공조직의 임상 실패의 주된 원인으로 알려져 있다. 최근에 항석회화 효과를 높이고자 기전이 다른 여러 처치를 병합하는 시도들이 보고되고 있다. 본 연구에서는 작용기전이 다른 ethanol, L-lysine, $NaBH_4$을 병합 처리하였을 때 예상되는 상승 효과를 석회화와 조직의 신축력(elasticity)을 통해 알아보고자 하였다. 대상 및 방법: 0.625% Glutaraldehyde ($4^{\circ}C$에서 2일, 상온에서 7일간)고정한 돼지 심낭을 80% Ethanol (상온에서 1일), 혹은 0.1 M L-lysine ($37^{\circ}C$에서 2일), 혹은 0.1 M $NaBH_4$ (상온에서 2일)로 처리 한 후 각각의 두께(thickness)와 장력(tensile strength)을 측정하였다. 각각의 항석회화 처리한 돼지심낭을 생후 3주된 쥐의 피하조직에 이식하고 8주 뒤 칼슘을 정량하고 조직학적 소견을 관찰하였다. 결과: 0.625% glutaraldehyde 고정만 시행한 군($51.2{\pm}8.5$ ug/mg)과 비교하여 80% Ethanol 처리한 군($13.6{\pm}10.0$ ug/mg, p=0.008)과, L-lysine 처리한 군($15.3{\pm}1.0$ ug/mg, p=0.002), 그리고 80% Ethanol과 L-lysine 처리한 군($16.1{\pm}11.1$ ug/mg, p=0.012)은 통계적으로 의미 있게 칼슘의 침착량이 적었지만, $NaBH_4$만 처리한 군($65.7{\pm}61.8$ ug/mg, p=0.653)과 80% Ethanol, L-lysme, $NaBH_4$로 모두 처리한 군($92.9{\pm}58.3$ ug/mg, p=0.288)은 칼슘의 침착량이 더 많았다. 80% Ethanol과 L-lysine으로 처리한 군과 80% Ethanol, L-lysine, $NaBH_4$로 모두 처리한 군의 장력/두께 비율(tensile strength/thickness ratio)은 각각 $7.60{\pm}1.55$, $7.47{\pm}1.85$로 glutaraldehyde 고정만 시행한 군의 $4.75{\pm}1.88$보다 증가되어 있는 경향을 보였다(p=0.76, p=0.33). 결론: Ethanol과 L-lysine을 돼지심낭에 병합처치 하였을 때, Ethanol과 L-lysine을 단독처치 하였을 때와 비교하여, 비슷한 항석회화 효과와 조직의 신축력을 증가시키는 경향을 보였지만 병합처치에 의한 상승효과를 확인하지는 못하였다. $NaBH_4$는 단독처치 혹은 병합처치하였을 때 모두 석회화를 증가시키는 경향을 보였다.