Jyotirmay Chanda

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.

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.

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.

Use of the glutaraldehyde-chitosantreated 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.

In vitro and in vivo calcification of vascular bioprostheses

Efficacy of different chemical treatments on calcification of vascular graft in vitro and in vivo was studied. Culture medium-filled rat aortas were separately treated in 0.2% glutaraldehyde and epoxy compound, and photooxidized in 0.01% methylene blue for a shorter period (group 1). Another group of rat aortas were separately treated in the same chemicals for a longer period (group 2). All fresh and treated aortas of both groups were cultured for 21 days in an organ culture medium and implanted (except for group 1) in weanling rats for five months. Histology and immunohistochemistry revealed that differently treated aortas of group 1 grow and calcify, and the smooth muscle cells between elastin fibers are the primary site of calcium deposition. In contrast, differently treated aortas of group 2 neither grew, nor did calcify in the medium except the epoxy compound cross-linked aorta of group 2 which did not grow but did calcify. Untreated aorta did not calcify. All fresh and differently treated aortic homografts calcified severely in rats. Our whole arterial segment-calcification system would be useful for analyzing the molecular and cellular mechanisms of both bioprosthetic and atherosclerotic calcification of vascular graft. New anticalcification technique is the only hope for better outcome of future vascular bioprostheses.

Heparin coupling in inhibition of calcification of vascular bioprostheses.

Inhibitory effect of heparin coupling on calcification of bioprosthetic vascular grafts of different origin was studied. Heparin-bonded (Hep) and 0.625% glutaraldehyde-cross-linked (GA) segments of porcine thoracic aorta (AO), pulmonary artery (PA), jugular vein (JV) and rabbit aorta (RA) were implanted subcutaneously in weanling rats for 5 months. Heparin bonding is ineffective in prevention of calcification of JV (Hep: Ca, 159 +/- 32.26 mg g-1; GA: Ca, 193.55 +/- 17.81; p = 0.075) and RA (Hep: Ca, 150.17 +/- 14.78; GA: Ca, 192.12 +/- 26.61; p = 0.015). Calcium content of heparin-coupled PA and AO was significantly less when compared with their GA-treated counterparts. Calcification inhibition was achieved to a greater extent in heparin-bonded PA (Hep: Ca = 22.62 +/- 5.72, GA: Ca = 115.99 +/- 21.91, p < 0.0001) than in the AO coupled to heparin (Hep: Ca = 63.77 +/- 22.75, GA: Ca = 150.40 +/- 35.21, p < 0.0001). Elastin fibers were the predominant site of calcification in all explanted vascular grafts. Heparin-bonded porcine pulmonary artery is seemed to be the best among all vascular bioprostheses in this study.

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.

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.

Prevention of Calcification in Glutaraldehyde-Treated Porcine Aortic and Pulmonary Valves

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.

Inhibitory effect of photooxidation on intimal and medial thickening of saphenous vein

BACKGROUND The inhibitory effect of short-term photooxidation on medial and neointimal proliferation of human saphenous vein was investigated. METHODS Culture medium-filled surgically prepared saphenous vein segments were photooxidized in 0.01% methylene blue solution for 5 minutes. Photooxidized and nonphotooxidized saphenous veins were checked for viability of endothelial cells by culturing vein segments for 21 days followed by histologic and immunohistochemical studies. RESULTS Endothelial cells of saphenous vein segments remained unaffected after photooxidation. Both the intima and media of nonphotooxidized veins became highly cellular and thickened because of the proliferation and migration of smooth muscle cells. Like precultured fresh saphenous vein, intimal (0.031+/-0.017 mm; p=0.0067) and medial thicknesses (0.702+/-0.123 mm; p < 0.0001) and proliferating cell nuclear antigen-positive cell count (14+/-8/mm2; p=0.0005) of cultured photooxidized veins were significantly less than those of cultured nonphotooxidized veins (intimal thickness, 0.059+/-0.041 mm; medial thickness, 0.997+/-0.228 mm; proliferating cell nuclear antigen positive cell count, 34+/-16/mm2. CONCLUSIONS Methylene blue-induced short-term photooxidation is effective in inhibition of intimal and medial thickening of saphenous vein.