From 1983 to 1992, 366 patients received 407 Mitroflow pericardial bioprostheses at our institution. Mean age was 62 +/- 14 years (range: 15-86 years). There were 229 isolated aortic valve replacements (AVR), 96 isolated mitral valve replacements (MVR), 39 double mitral and aortic valve replacements (DVR) and four tricuspid replacements. Mean follow up was 6 +/- 2.33 years ranging from 1.67 to 10.9 years. Total follow up was 1791 patient-years. Overall survival was 77.2 +/- 2.2% at five and 56.2 +/- 6.4% at 10 years. It was 74 +/- 3% and 56.2 +/- 5.3% after AVR, 78.3 +/- 4.4% and 55.7 +/- 8.8% after MVR, 81 +/- 6.4% and 36.6 +/- 16.5% after DVR at five and 10 years, respectively. Freedom from structural valve deterioration (SVD) was 95 +/- 1.2% and 36.7 +/- 8.1% at five and 10 years for all valves, 96.9 +/- 1.3% and 39.2 +/- 9.8% for AVR, 91.7 +/- 3.2% and 36.4 +/- 10% for MVR. There was no difference in freedom from SVD between AVR and MVR. The freedom from SVD in patients older than 70 years of age was 100% and 93.9 +/- 5.8% at five and 10 years, respectively. Freedom from reoperation was 94.7 +/- 1.37% and 28.36 +/- 7.5% at five and 10 years for all valves, 96.2 +/- 1.5% and 38.6 +/- 9.7% for AVR, 91.7 +/- 3.2% and 36.4 +/- 10% for MVR. The denaturation process did not lead to acute hemodynamic deterioration. Pathologic findings were cuspal tears (one or more) associated with structural tissue changes.(ABSTRACT TRUNCATED AT 250 WORDS)

From 1983 to 1992, 366 patients received 407 Mitroflow pericardial valves. Mean age was 62 +/- 14 years. Average follow-up was 72 +/- 28 months. Total follow-up was 1,791 patient-years. Overall survival in all patients was 77.2% +/- 2.2% at 5 years and 56.2% +/- 6.4% at 10 years. Freedom from structural valve deterioration was 95% +/- 1.2% and 36.7% +/- 8.1% at 5 and 10 years for all valves, 96.9% +/- 1.3% and 39.2% +/- 9.8% for aortic valve replacement, and 91.7% +/- 3.2% and 36.4% +/- 10% for mitral valve replacement (p = not significant). The freedom from structural valve deterioration in patients older than 70 years of age was 100% and 93.9% +/- 5.8% at 5 and 10 years, respectively. At 10 years, linearized rate of thromboembolism was 0.73% +/- 0.2% per patient-year and freedom from valve-related mortality for all valves was 88.8% +/- 2.8%. The best indication for the implantation of a Mitroflow valve is mitral or aortic disease in patients more than 70 years of age.

A small caliber vascular prosthesis obtained from an ovine internal thoracic artery (3.8-4.5 mm ID) fixed with a polyepoxy compound and treated with heparin has been evaluated. Cytocompatibility was evaluated in vitro using human endothelial cells (HEC). HEC were obtained from human saphenous vein and cultivated in culture medium supplemented with 25% human serum. Graft segments were rinsed using a standard protocol proposed by the manufacturer. Tissue reaction was tested on a rabbit model of subcutaneous implantation. The patency rate and healing patterns were evaluated comparatively with polytetrafluorethylene (PTFE) 4 mm ID prosthesis in a canine model of carotid interposition. Cytocompatibility assay showed that there was low adhesion on vascular grafts (20 +/- 2% of endothelial cells seeded) and no growth of HEC on the graft surface. The graft patency rate was 55% in both groups, and actuarial freedom from occlusion was not different at 3 months (37.7 +/- 15% in Denacol-fixed grafts versus 38.1 +/- 14% in PTFE). Histological studies on the biological grafts shows a frequent neointimal hyperplasia at the anastomosis (5/12), a lack of endothelial cells lining the graft surface, a good preservation of the media, and a moderate inflammatory response in the adventicia. The Denacol-fixed graft has presented excellent surgical properties and preservation of the histological structure. Nevertheless, the patency rate was not improved when compared with the PTFE control graft.

The aim of this study was to detect biologic factors in the structural deterioration of bioprosthetic heart valves. Prostheses were removed from patients after 4-8 years of implantation and submitted to biochemical and morphologic assays. Successive staining of biologic sections revealed colocalization of lipids and glycosaminoglycans underneath calcifications in the disintegrated extracellular matrix. On biochemical assays, the amidolysis of synthetic peptide substrates indicated thrombin, plasmin, and tissue plasminogen activator activities in the nonhemocompatible leaflets; 0.15 mol NaCl, 0.05 mol Tris, and 5 mmol CaCl2 extracts from the prostheses cleaved the peptide substrate for collagenase and lysed gelatin gels. Polyacrylamide gel electrophoresis in sodium dodecyl sulfate disclosed the presence of low molecular mass polypeptides in extracts of the deteriorated prostheses. The detection of plasmin and collagenolytic enzyme(s), and the known broad proteolytic activity of plasmin, may point to the role of activation of the fibrinolytic system in the proteolytic degradation of bioprosthetic valves.

A large number of coronary patients referred for coronary bypass surgery receive platelet anti-aggregant therapy which has the disadvantage of increasing per and postoperative haemorrhage. The aim of this study was to assess the effects of aprotinin in 60 patients under platelet antiaggregant therapy (aspirin 250 mg/day) for over 30 days before surgery for coronary bypass grafting. The clinical (age, weight, diagnosis, bypass time, number of grafts) and biological features (preoperative haemoglobin concentration, platelet count and fibrinogen levels) were identical in a group treated by aprotinin (Group A, n = 30) and a control group (Group B, n = 30). The aprotinin treatment protocol was an intravenous injection of 2 million KIU (kallicrein inhibitory units) before starting the cardiopulmonary bypass and 2 million KIU in the filling liquid of the bypass circuit.A significant reduction in blood loss was observed in Group A with respect to Group B (370 +/- 154 ml versus 651 +/- 323 ml at day 1, p < 0.01). The haemoglobin concentration was higher in Group A than in Group B (11.9 +/- 1,6 g/100 ml versus 10.3 +/- 1.4 g/100 ml, p < 0.001) and fewer patients required blood transfusion (Group A: 16 % versus Group B: 43 %, p = 0.04). In conclusion, high doses of aprotinin given to patients on aspirin therapy undergoing coronary bypass surgery, significantly reduce postoperative blood loss and the number of patients transfused.

Isolated aortic (n = 107), mitral (n = 63), and tricuspid (n = 1) valve replacement and 28 double-valve replacements were performed with a second generation of pericardial valves, the Mitroflow valve, in 199 patients from March 1983 to December 1986. Follow-up (total, 1,058 patient-years) was extended to 106 months and 91.5% complete. Mean age was 58 +/- 13 years. The operative mortality included 22 deaths, non-cardiac-related in 7. The actuarial probability of survival for all patients was 66% +/- 4% at 8.5 years. There were no significant differences between patients with aortic valve replacement, mitral valve replacement, or double-valve replacement. The rate of thromboembolic events, antithromboembolic therapy-related hemorrhage, periprosthetic leak, and endocarditis is extremely minimal. Structural valve dysfunction occurred at a rate of 3.2% +/- 0.5%/patient-year. Actuarial freedom from the event was 94.6% +/- 1.7% at 5 years and 63.7% +/- 6.5% at 8.5 years for all valves. There were no difference in structural valve dysfunction rate between patients having aortic, mitral, or double-valve replacement. Thirty-five patients were reoperated on (3.4 +/- 0.6%/patient-year for all). The rate of all valve-related morbidity and mortality was 5.6% +/- 0.7%/patient-year for all patients, actuarial freedom from the event being 44% +/- 7% at 8.5 years. These data suggest that the excellent hemodynamic characteristics of the valve are balanced by a risk of valve failure that is slightly increased when compared with porcine valves.

A device permitting homogeneous endothelial cell seeding of a small-caliber arterial prosthesis has been developed. The prosthesis is maintained firmly attached to a rotative scaffolding device. This device is activated by an electrical motor at constant and adjustable speed. The whole system is maintained at 37 degrees C in a cell culture incubator. The 4 mm internal diameter polytetrafluoroethylene (PTFE) prosthesis was coated with biological glue and seeded with human saphenous vein endothelial cells obtained by mechanical detachment. Cell seeding density was 2.10(4) cells/cm2 (Group A, n = 6) or 10(5) cells/cm2 (Group B, n = 6). Rotation speed was 8 revolutions per hour (rph) during 90 min. Analysis of the homogeneity of cell seeding was permitted by cell counts on five different segments of the prosthesis. Each longitudinal segment was analyzed at three different subsegments of the circumference. The average adhesion was 43 +/- 4% in Group A and 38% +/- in Group B of seeded cells. No difference could be observed between the different segments and subsegments. In the two groups, cells were spread, and in Group B, a complete endothelial cell layer was obtained on the graft surface. This study permits validation of the device to allow homogeneous cell seeding in an arterial prosthesis.

A large number of coronary patients referred for coronary bypass surgery receive platelet anti-aggregant therapy which has the disadvantage of increasing per and postoperative haemorrhage. The aim of this study was to assess the effects of aprotinin in 60 patients under platelet antiaggregant therapy (aspirin 250 mg/day) for over 30 days before surgery for coronary bypass grafting. The clinical (age, weight, diagnosis, bypass time, number of grafts) and biological features (preoperative haemoglobin concentration, platelet count and fibrinogen levels) were identical in a group treated by aprotinin (Group A, n = 30) and a control group (Group B, n = 30). The aprotinin treatment protocol was an intravenous injection of 2 million KIU (kallikrein inhibitory units) before starting the cardiopulmonary bypass and 2 million KIU in the filling liquid of the bypass circuit. A significant reduction in blood loss was observed in Group A with respect to Group B (370 +/- 154 ml versus 651 +/- 323 ml at day 1, p < 0.01). The haemoglobin concentration was higher in Group A than in Group B (11.9 +/- 1.6 g/100 ml versus 10.3 +/- 1.4 g/100 ml, p < 0.001) and fewer patients required blood transfusion (Group A: 16% versus Group B: 43%, p = 0.04). In conclusion, high doses of aprotinin given to patients on aspirin therapy undergoing coronary bypass surgery, significantly reduce postoperative blood loss and the number of patients transfused.

A consecutive series of 188 Mitroflow pericardial bioprostheses were inserted in 166 patients between 1st January 1983 and 31st December 1985. Twenty-two valves had to be removed from 16 patients after a mean follow up period of 78 months (range 58-92 months) for aortic, 73 months (65-79 months) for mitral and 78 months (48-103 months) for double valve replacements. All but one reoperations for primary tissue failure were carried out as elective surgical procedures. The most important cause of failure was collagen degeneration, seen in all explanted valves. The areas of degeneration were the major sites of origin of calcification, which was seen in 11 valves (50%). Ten valves (45%) showed features suggestive of lipid infiltration, extensive fatty acid deposition being identified in one and a typical atheromatous reaction in another. In contrast to the Ionescu-Shiley valve, the mode of failure was tear originating at the top of the commissure, associated with major structural changes in the tissue. Excessive pannus ingrowth was observed in 11 valves (50%). The universal presence of tissue degeneration in the glutaraldehyde treated pericardial leaflets of the Mitroflow bioprostheses explanted and examined in this study questions the adequacy of the methods employed in the harvesting and/or processing and/or preservation of this valve. We have, therefore, discontinued using the Mitroflow bioprosthesis. However, the slow deterioration of the Mitroflow bioprosthesis permits elective reoperation; preventive removal of functioning valves is therefore not indicated.