BACKGROUND: The problem of calcification in porcine aortic (AVs) and pulmonary (PVs) valves and its relationship to glutaraldehyde (GA) is of current interest. We proposed an anticalcification treatment to develop noncalcifying porcine AVs and PVs. METHODS: Porcine AVs and PVs were cross-linked in GA. Partially degraded heparin was coupled to the GA-treated AVs and PVs through intermediate surface-bound substrate containing amino groups. Control AVs and PVs were cross-linked in 0.625% GA but had no heparin coupling. All specimens were implanted subdermally in 3-week-old rats for 5 months for calcification studies. RESULTS: Control AVs (Ca, 233.69 +/- 42.61 mg/g) and PVs (Ca, 181.48 +/- 4.06 mg/g) were severely calcified. Coupling of partially degraded heparin revealed complete prevention of calcification in GA-treated AVs (Ca, 0.73 +/- 0.27) and PVs (Ca, 1.125 +/- 0.22 mg/g) implanted subcutaneously in weanling rats for 5 months. CONCLUSIONS: The proposed anticalcification treatment is effective in preventing calcification of GA-treated AVs and PVs implanted subcutaneously in weanling rats for 5 months.

Animals↗

PubMed1997

New-generation valved conduit: an experimental study.

OBJECTIVE: An ideal valved conduit to repair complex congenital heart defects is yet to be developed. In this study we have evaluated the merits of our newly developed calcification-free biologic valve incorporated in a compatible conduit of biologic origin in an animal model. METHODS: Porcine aortic valves and main pulmonary arteries were cross-linked in glutaraldehyde, followed by coupling to partially degraded heparin through an intermediate surface-bound substrate containing amino groups. Because commercially available valves are treated only with glutaraldehyde, control aortic valves and main pulmonary arteries were cross-linked in 0.625% glutaraldehyde. Valved conduits were fabricated from main pulmonary arteries, which were sewn to the aortic and ventricular ends of aortic valves. Valved conduits were examined for calcification and other pathologic changes after being implanted in the descending thoracic aorta in juvenile sheep for 5 months. RESULTS: Severe calcification was noticed in all layers of cusps (calcium, 231.86 +/- 17.90 mg/gm) and aortic wall (calcium, 123.24 +/- 24.72 mg/gm) of aortic valves and main pulmonary arteries (calcium, 135.43 +/- 26.63 mg/gm) of valved conduits treated with 0.625% glutaraldehyde. Cusps (calcium, 1.28 +/- 0.22 mg/gm) of the aortic valve of heparin-bonded conduits did not calcify at all. Only sparse calcific deposits were noticed in the medial layer of the aortic wall (calcium, 25.90 +/- 22.79 mg/gm) of aortic valves and main pulmonary arteries (calcium, 9.64 +/- 10.79 mg/gm) of the valved conduits coupled to heparin. CONCLUSION: Heparin coupling is effective in preventing calcification of glutaraldehyde cross-linked valved conduits implanted in the systemic circulation of juvenile sheep.

Animals↗

PubMed1997

Concentration of glutaraldehyde in fixation of bioprosthetic valves.

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Animals↗

PubMed1997

Heparin in calcification prevention of porcine pericardial bioprostheses.

Calcific degeneration is the main cause of failure of glutaraldehyde-treated xenograft heart valve substitutes implanted in humans. Coupling of heparin through an intermediate surface-bound substrate containing amino groups showed complete prevention of calcification of glutaraldehyde-treated porcine pericardium implanted subdermally in weanling rats for 5 months (heparin bonded pericardium: calcium, 0.625 +/- 0.24 mg g(-1); glutaraldehyde-only-treated pericardium: calcium, 228.32 +/- 37.39 mg g(-1); P < 0.0001). Conceivably, inactivation of unpaired aldehyde moieties present in bioprostheses after exposure to glutaraldehyde by amino compounds followed by blocking the potential binding sites of the graft with a surface modifying agent like heparin would be the key steps in the prevention of calcification and degeneration of glutaraldehyde-treated biological tissue grafts.

Animals↗

PubMed1997

Valved conduit in the descending thoracic aorta in juvenile sheep: a useful, cost-effective model for accelerated calcification study in systemic circulation.

To evaluate the efficacy of any new anticalcificant in bioprostheses, a cost-effective and easy circulatory model is proposed. Calcification of 0.625% glutaraldehyde-treated porcine aortic valved conduits implanted in the descending thoracic aorta in 11 juvenile sheep for 5 months was compared with that of leaflets of glutaraldehyde-treated porcine aortic valve implanted subcutaneously in 3-week-old male Wistar rats for the same period. Cusps of valved conduits (Ca, 205.41 +/- 16.24 mg g(-1)) in sheep and aortic valve leaflets in rats (Ca, 235.21 +/- 45.25 mg g(-1)) (P = 0.0299) were severely calcified. Morphological characteristics of calcification of all explants were virtually identical. This model provides a model for testing calcification that lies between the subcutaneous weanling rat model and orthotopic whole valve replacement on the left side of the heart. It is less costly and easier to perform than the latter, but does provide exposure to the bloodstream under pressure, which the rat model does not.

Animals↗

PubMed1997

Is the dog a useful model for accelerated calcification study of cardiovascular bioprostheses?

Chitosan posttreatment has been shown to be effective in prevention of calcification of the glutaraldehyde treated bovine pericardium when implanted subdermally in rats for 12 weeks. The efficacy of chitosan posttreatment in complete calcium mitigation of the glutaraldehyde treated porcine aortic valves implanted in the right side of the heart in dogs was well-documented in our previous study. In this study, an attempt has been made to evaluate the merit of the chitosan posttreatment in prevention of calcification of the glutaraldehyde (GA) treated porcine aortic valved conduits in the systemic circulation in dogs for a period of 5 months. Eleven mongrel dogs underwent left thoracotomy. Porcine aortic valved conduits treated with 0.625% GA (n = 5) and GA-chitosan (n = 6) were implanted in the descending thoracic aortas of the dogs for 5 months. Gross histological observations showed no calcification in either the 0.625% GA treated or in the GA-chitosan treated valved conduits at 5 months. This was confirmed by results of quantitative analyses for calcium in each explant. There was no significant difference in calcium content between the GA only (Ca, 0.43 +/- 0.26 mg/g) and GA-chitosan treated (Ca, 0.51 +/- 0.19 mg/g; p = 0.5959) valved conduits. This study suggests that the dog is not a suitable model for evaluating the efficacy of a calcium mitigating agent in bioprostheses implanted in systemic circulation.

Animals↗

PubMed1997

Apico-aortic shunt: a support technique during surgery on the descending thoracic aorta.

To find out whether apico-aortic shunt may become an alternative support technique during surgery on the descending thoracic aorta, performance between apico-aortic shunt and aorto-aortic shunt was compared. In 5 sheep weighing 20-25 kg, apico-aortic shunt and aorto-aortic shunt were instituted with covalently bonded heparin coated polyvinyl tube (internal diameter 5 mm). After clamping the descending thoracic aorta, apico-aortic shunt and aorto-aortic shunt were opened for 30 minutes each. Proximal pressure was elevated to 200 mmHg and distal pressure was fallen to 55 mmHg after clamping the descending thoracic aorta. Opening of apico-aortic shunt and aorto-aortic shunt decreased proximal pressure to 178 +/- 14.8 and 173 +/- 12.0 mmHg, respectively (p = 0.57), and raised distal pressure to 82.4 +/- 7.8 and 90.0 +/- 3.5 mmHg, respectively (p = 0.83). The baseline blood flow of the descending thoracic aorta was 1.4-1.5 l/min. Apico-aortic shunt and aorto-aortic shunt were 0.76 +/- 0.16 and 0.80 +/- 0.22 l/min, respectively (p = 0.67). Blood gas tension, pH and BE measurement showed no significant change and difference between apico-aortic shunt and aorto-aortic shunt, and before and after clamping the descending thoracic aorta. Using apico-aortic shunt, interposition of bioprosthetic valved conduit in the descending thoracic aorta in 10 sheep was successfully performed without paraplegia and any other complications. We concluded that apico-aortic shunt may become an alternative support technique during surgery on the descending thoracic aorta in some specific situations.

Animals↗

PubMed1996

Surgical treatment of isolated secundum atrial septal defect in patients more than 50 years old.

BACKGROUND: Arrhythmia-related thromboembolic accidents continue to occur in patients even after closure of secundum atrial septal defect. Older age is usually not a contraindication to the repair of an atrial septal defect. To assess the importance of the type of management in elderly patients with atrial septal defect our clinical experience is reviewed. METHODS: Between 1974 and 1994, 49 patients 50 years of age or older (average, 57.4 years) underwent surgical closure of secundum atrial septal defect. All patients have been followed up for 2 to 21 years (mean, 9.7 years). RESULTS: There were no operative deaths. Functional classes in most of the patients were improved after operation. There were two cerebrovascular thromboembolic accidents with one permanent neurologic dysfunction, hemiparesis, and one septal dehiscence in the early postoperative period. One patient (2%) died of renal failure 6 years after operation, late arrhythmias developed in 3 patients (6%), 3 patients had a late stroke (6%), and 1 patient was not available for follow-up. CONCLUSIONS: Long-term operative results are satisfactory and beneficial to the quality of life in elderly patients. Because there is no safe and effective nonsurgical alternative to surgical closure, atrial septal defect repair in elderly patients without severe pulmonary vascular disease should not be delayed once the diagnosis had been made.

Age Factors↗

PubMed1996

Use of the glutaraldehyde-chitosan-treated porcine pericardium as a pericardial substitute.

The efficacy of chitosan post-treatment of glutaraldehyde-treated porcine pericardial substitute for the prevention of postoperative epicardial reaction and adhesion formation in mongrel dogs has been assessed. Glutaraldehyde (0.625%)-treated porcine pericardium showed moderate to dense adhesions to the heart and other underlying organs with moderate to severe epicardial reaction. None to minimal epicardial reaction without adhesion was observed in glutaraldehyde-treated porcine pericardium post-treated with chitosan at 5 months. Presumably, chitosan post-treatment prevents the slow release of residual glutaraldehyde and reduces the toxicity of the glutaraldehyde-treated implants, minimizing the chance of adhesion formation and epicardial reaction.

Animals↗

PubMed1996

Efficacy of the chitosan posttreatment in calcification prevention of the glutaraldehyde-treated porcine aortic noncoronary cusp implanted in the right ventricular outflow tract in dogs.

Calcific tissue failure results in poor performance of the bioprosthetic heart valve. Chitosan post-treatment has been shown to be effective in calcification prevention of the glutaraldehyde-treated bovine pericardium when implanted subdermally in rats for 12 weeks. The present study investigated the effectiveness of the chitosan posttreatment in prevention of calcification of the glutaraldehyde-treated porcine aortic noncoronary cusp 5 months after implantation in the right ventricular outflow tract (RVOT) in mongrel dogs. Either 0.625% glutaraldehyde-treated (Group 1, n = 6) or glutaraldehyde-chitosan-treated (Group 2, n = 6) porcine aortic noncoronary cusp with the aortic wall was sewn to the RVOT. Gross histological observations showed moderate calcification of the glutaraldehyde-treated cusps, but no calcification was noticed in the glutaraldehyde-chitosan-treated grafts at 5 months. This was confirmed by results of quantitative analyses for calcium in half of each explanted cusp with aortic wall. The calcium content of the 0.625% glutaraldehyde-treated cusps (Ca, 40.6 +/- 24.9 mg/g dry wt) was significantly (p < 0.01) higher than that of glutaraldehyde-chitosan-treated cusps (Ca, 1.3 +/- 0.29 mg/g dry wt). These findings suggest that chitosan post-treatment is effective in complete calcium mitigation of the glutaraldehyde-treated porcine aortic noncoronary cusps implanted in the RVOT in dogs.

Animals↗

PubMed1995

Prevention of calcification of heart valve bioprostheses: an experimental study in rat.

To eliminate highly antigenic substances, bovine pericardium was washed in 5% sodium chloride (NaCl) for 24 hours, followed by incubation in trypsin for 40 minutes. To achieve adequate fixation, NaCl-trypsin-treated pericardium was preserved in glutaraldehyde (GA) solution with gradually increasing concentrations from 0.1% to 0.25%. To inactivate the free aldehyde groups and residual GA on the surface of the implant, NaCl-trypsin-GA-treated pericardial samples were posttreated separately with 1% lysine, 8% monosodium glutamate, and 4% chitosan. Fresh (untreated) and 0.1%, 0.2%, and 0.625% GA-treated and NaCl-trypsin-GA-treated pericardial specimens were prepared for comparative study. All samples were implanted subdermally in rats for 2, 4, 8, and 12 weeks for calcification studies. Morphologic and chemical analyses showed mild calcification in fresh pericardia (Ca, 10.5 +/- 1.25 micrograms/mg, von Kossa +) and in glutamate-posttreated pericardia (Ca, 11.5 +/- 3.45 micrograms/mg, von Kossa +). Calcium was practically undetectable in chitosan-posttreated implants (Ca, 1.1 +/- 0.27 micrograms/mg, von Kossa 0), whereas severe calcification was noticed in the rest of the samples (mean Ca greater than 200.0 micrograms/mg, von Kossa ) at 12 weeks. This study suggests that posttreatment with an amino compound such as chitosan would prevent the calcification of GA-treated bioprostheses at an early implantation stage, but elimination of antigenic factors and adequate GA fixation would prevent tissue degeneration, thus enabling the prosthesis to function over a long period.

Animals↗

PubMed1994

Use of glutaraldehyde-gentamicin-treated bovine pericardium as a wound dressing.

Glutaraldehyde (GA)-pretreated gentamicin post-fixed bovine pericardium has been evaluated as a wound dressing in this study. Two excisions approximately 7 x 4 cm, each of full thickness skin, from the upper and lower parts down to, but not including, the panniculus carnosus were made from the back of the guinea pig. The skin excised from the upper part was placed on the wound bed of the lower part as an autograft, whereas the upper wound was closed using 5% sodium chloride-trypsin-0.1% GA-0.048% gentamicin-treated bovine pericardium and sutured for comparative study. The wounds were inspected every 3-6 d for infection and exudation. Histopathological studies were performed at weekly intervals in the post-operative period. At the fifth week, a very thin linear scar on the epidermal aspect without remarkable contracture was observed and histopathology showed the completion of epithelization across the wounds in all cases. This study demonstrates that GA-pretreated, gentamicin-post-fixed bovine pericardium may be used as an alternative biological dressing in the case of large wounds.

Animals↗

PubMed1994

Anticalcification treatment of pericardial prostheses.

The aim of the present study was to develop a chemical treatment to eliminate highly antigenic substances, to standardize the glutaraldehyde fixation procedure, to determine the dominant factors contributing to the calcification process and to understand the role of macromolecules like chitosan in the prevention of calcification of bioprosthetic heart valves. Bovine pericardium treated with 5% sodium chloride-trypsin-glutaraldehyde (GA)-chitosan did not calcify at 12 wk in the rat (calcium, 1.1 +/- 0.27 mg/g; von Kossa, 0). Slow release of residual GA from the bioprosthesis and free aldehyde groups on that are still considered the dominant factors for enhancing calcification of GA-treated bioprostheses.

Animals↗

PubMed1994

Posttreatment with amino compounds effective in prevention of calcification of glutaraldehyde treated pericardium.

An attempt has been made to compare the role of different amino compounds in prevention of calcification of glutaraldehyde (GA)-treated pericardium implanted subcutaneously in the rat for 12 weeks. GA pretreated pericardial samples were postfixed separately with glycine, albumin, gentamicin, glycine + gentamicin, and albumin + gentamicin. Severe calcification was noticed in animals undergoing albumin or gentamicin postfixation. Mild calcification was observed in glycine and albumin + gentamicin postfixed materials whereas calcium was undetectable either chemically or morphologically in GA-pretreated pericardium postfixed with glycine + gentamicin (0.32 +/- 0.13.mg/g calcium, dry wt; von Kossa 0) at the 12th week of implantation in the rat.

Albumins↗