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Degenerative processes in bioprosthetic mitral valves in juvenile pigs.

Honge JL, Funder JA, Pedersen TB, Kronborg MB, Hasenkam JM - J Cardiothorac Surg (2011)

Bottom Line: Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively.Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves.In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark.

ABSTRACT

Background: Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs.

Materials: The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation.

Results: Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

Conclusions: Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.

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Histological imaging of the donor tissue (left) and host tissue in the stent-adjacent area (right). Non-vital, less basophilic cell remnants can be clearly seen (arrows). Inflammatory cell response is seen between the donor tissue and the fibrous sheath (H&E stain; ×400).
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Figure 3: Histological imaging of the donor tissue (left) and host tissue in the stent-adjacent area (right). Non-vital, less basophilic cell remnants can be clearly seen (arrows). Inflammatory cell response is seen between the donor tissue and the fibrous sheath (H&E stain; ×400).

Mentions: H&E stain revealed the presence of nonvital donor cell remnants throughout the valve tissue. These cells were characterized by a negative vimentin stain and appeared less basophilic compared with host cells. Fibrous sheath formation was observed in all valves to various degrees; in two valves, the fibrous sheath stretched from both the atrial and ventricular sides to the base of the cusp. Between the donor tissue and the fibrous sheath, inflammatory cells could be seen in small numbers in all valves (Figure 3). Fibroblast ingrowth was limited to the fibrous sheath and as a part of an inflammatory response in the stent-adjacent area. No cusp ingrowth of fibroblasts was seen in any of valves. Host cells were almost absent in the cusp tissue except for in one valve where infiltration of macrophages and lymphocytes could be noted. Only a few minor fibrin depositions were observed on the surface of the valves, except for in one valve where larger depositions could be seen. Von Kossa stains revealed severe calcification of the stent adjacent area, annulus, and myocytes in three valves. Intrinsic calcification of the cusp was observed in two valves (Figure 4). Inflammatory cells consisting of macrophages and lymphocytes were associated with the calcifications seen in the stent-adjacent areas, but no or only very few inflammatory cells were seen in the presence of cusp calcification. Inflammatory cells were observed in the outer parts of all valves and to a larger degree if a myocardial muscle shelf was present. The cusp tissue, collagen, and elastin appeared well preserved, with clear demarcations of the different laminae except for the calcified areas of the cusps (Figure 5). Intracuspal erythrocytes could be seen in the cusps of three valves but in limited amounts. Limited tissue fragmentation and collagen loosening were only observed in the basal part of two valves (Figure 6). Von Willebrand factor-positive cells could only be seen superimposing parts of the fibrous sheath. No single von Willebrandt factor-positive cells or continuous single-cell layer could be seen in any of the cusps.


Degenerative processes in bioprosthetic mitral valves in juvenile pigs.

Honge JL, Funder JA, Pedersen TB, Kronborg MB, Hasenkam JM - J Cardiothorac Surg (2011)

Histological imaging of the donor tissue (left) and host tissue in the stent-adjacent area (right). Non-vital, less basophilic cell remnants can be clearly seen (arrows). Inflammatory cell response is seen between the donor tissue and the fibrous sheath (H&E stain; ×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3117695&req=5

Figure 3: Histological imaging of the donor tissue (left) and host tissue in the stent-adjacent area (right). Non-vital, less basophilic cell remnants can be clearly seen (arrows). Inflammatory cell response is seen between the donor tissue and the fibrous sheath (H&E stain; ×400).
Mentions: H&E stain revealed the presence of nonvital donor cell remnants throughout the valve tissue. These cells were characterized by a negative vimentin stain and appeared less basophilic compared with host cells. Fibrous sheath formation was observed in all valves to various degrees; in two valves, the fibrous sheath stretched from both the atrial and ventricular sides to the base of the cusp. Between the donor tissue and the fibrous sheath, inflammatory cells could be seen in small numbers in all valves (Figure 3). Fibroblast ingrowth was limited to the fibrous sheath and as a part of an inflammatory response in the stent-adjacent area. No cusp ingrowth of fibroblasts was seen in any of valves. Host cells were almost absent in the cusp tissue except for in one valve where infiltration of macrophages and lymphocytes could be noted. Only a few minor fibrin depositions were observed on the surface of the valves, except for in one valve where larger depositions could be seen. Von Kossa stains revealed severe calcification of the stent adjacent area, annulus, and myocytes in three valves. Intrinsic calcification of the cusp was observed in two valves (Figure 4). Inflammatory cells consisting of macrophages and lymphocytes were associated with the calcifications seen in the stent-adjacent areas, but no or only very few inflammatory cells were seen in the presence of cusp calcification. Inflammatory cells were observed in the outer parts of all valves and to a larger degree if a myocardial muscle shelf was present. The cusp tissue, collagen, and elastin appeared well preserved, with clear demarcations of the different laminae except for the calcified areas of the cusps (Figure 5). Intracuspal erythrocytes could be seen in the cusps of three valves but in limited amounts. Limited tissue fragmentation and collagen loosening were only observed in the basal part of two valves (Figure 6). Von Willebrand factor-positive cells could only be seen superimposing parts of the fibrous sheath. No single von Willebrandt factor-positive cells or continuous single-cell layer could be seen in any of the cusps.

Bottom Line: Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively.Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves.In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Cardiothoracic and Vascular Surgery, Aarhus University Hospital, Skejby, Denmark.

ABSTRACT

Background: Glutaraldehyde-treated bioprosthetic heart valves are commonly used for replacement of diseased heart valves. However, calcification and wear limit their durability, and the development of new and improved bioprosthetic valve designs is needed and must be evaluated in a reliable animal model. We studied glutaraldehyde-treated valves 6 months after implantation to evaluate bioprosthetic valve complications in the mitral position in juvenile pigs.

Materials: The study material comprised eight, 5-month old, 60-kg pigs. All pigs received a size 27, glutaraldehyde-treated, stented, Carpentier-Edwards S.A.V. mitral valve prosthesis. After six months, echocardiography was performed, and the valves explanted for gross examination, high resolution X-ray, and histological evaluation.

Results: Five pigs survived the follow-up period. Preexplant echocardiography revealed a median peak and mean velocity of 1.61 m/s (range: 1.17-2.00) and 1.20 (SD = ±0.25), respectively, and a median peak and mean pressure difference of 10.42 mmHg (range: 5.83-16.55) and 6.51 mmHg (SD = ±2.57), respectively. Gross examination showed minor thrombotic depositions at two commissures in two valves and at all three commissures in three valves. High resolution X-ray imaging revealed different degrees of calcification in all explanted valves, primarily in the commissural and belly areas. In all valves, histological evaluation demonstrated various degrees of fibrous sheath formation, limited immunological infiltration, and no overgrowth of host endothelium.

Conclusions: Bioprosthetic glutaraldehyde-treated mitral valves can be implanted into the mitral position in pigs and function after 6 months. Echocardiographic data, calcification, and histological examinations were comparable to results obtained in sheep models and human demonstrating the suitability of the porcine model.

Show MeSH
Related in: MedlinePlus