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Objectives: Human subjects and Old World primates have high levels of antibody to galactose-α-1,3 galactose β-1,4-N-acetylglucosamine (α-Gal). Commercially available bioprosthetic heart valves of porcine and bovine origin retain the Gal antigen despite current processing techniques. Gal-deficient pigs eliminate this xenoantigen. This study tests whether binding of human anti-Gal antibody effects calcification of wild-type and Gal-deficient glutaraldehyde-fixed porcine pericardium by using a standard subcutaneous implant model. Methods: Expression of α-Gal was characterized by lectin Griffonia simplicifolia–IB4 staining. Glutaraldehyde-fixed pericardial disks from Gal-positive and Gal-deficient pigs were implanted into 12-day-old Wistar rats and 1.5-kg rabbits with and without prelabeling with affinity-purified human anti-Gal antibody. Calcification of the implants was determined after 3 weeks by using inductively coupled plasma spectroscopy. Results: The α-Gal antigen was detected in wild-type but not Gal-deficient porcine pericardium. Wild-type disks prelabeled with human anti-Gal antibody exhibited significantly greater calcification compared with that seen in antibody-free wild-type samples (mean ± standard error of the mean: 111 ± 8.4 and 74 ± 9.6 mg/g, respectively; P = .01). In the presence of anti-Gal antibody, a significantly greater level of calcification was detected in wild-type compared with GTKO porcine pericardium (111 ± 8.4 and 55 ± 11.8 mg/g, respectively; P = .005). Calcification of Gal-deficient pericardium was not affected by the presence of anti-Gal antibody (51 ± 9.1 and 55 ± 11.8 mg/g). Conclusions: In this model anti-Gal antibody accelerates calcification of wild-type but not Gal-deficient glutaraldehyde-fixed pericardium. This study suggests that preformed anti-Gal antibody present in all patients might contribute to calcification of currently used bioprosthetic heart valves. Gal-deficient pigs might become the preferred source for new, potentially calcium-resistant bioprosthetic heart valves. [Copyright &y& Elsevier]

Background: Although glutaraldehyde fixation is known to reduce immunogenicity and degeneration of heart valve bioprostheses, some degree of immunogenicity persists, which may trigger calcification. The aims of this study were to: (1) define the role of alpha-1,3-galactosyltransferase (α-Gal) antigen in valve calcification by comparing α-Gal–positive and α-Gal–deficient (GT-KO) pig pericardium; and (2) elucidate the role of human anti-Gal antibodies in the process of calcification and to determine the potential influence of different tissue-fixation techniques. Methods: Glutaraldehyde-treated pericardium from α-Gal–positive and GT-KO pigs, with or without pre-labeling with human anti-Gal antibodies, were implanted in rats during 1 month. Results: In glutaraldehyde-fixed pericardium, calcification levels were significantly lower in GT-KO pig pericardium (132.8 ± 5.8 μg/mg) as compared with α-Gal–positive pig pericardium (155.7 ± 7.1 μg/mg) (p < 0.015). In glutaraldehyde-fixed pig pericardium followed by a mix of formaldehyde, ethanol and Tween 80 (FET), the calcification levels were lower in GT-KO pig pericardium (0.35 ± 0.1 μg/mg) as compared with α-Gal–positive pig pericardium (4.6 ± 4.2 μg/mg). In glutaraldehyde-fixed pig pericardium + FET pre-incubated with human anti-Gal antibodies, calcification levels were significantly greater in α-Gal–positive pig pericardium (43.8 ± 8.5 μg/mg) as compared with GT-KO pig pericardium (5.7 ± 2.9 μg/mg) (p < 0.0001). Conclusions: This study demonstrates the role of α-Gal antigen and human α-Gal antibodies in the calcification process of valvular bioprostheses. It is suggested that GT-KO pig pericardium could be beneficial as a new source of material for heart valve bioprostheses. [Copyright &y& Elsevier]

Objective: Ischemic heart disease (IHD) is a leading cause of mortality with insufficient results of current therapies, most probably due to maintained endothelial dysfunction conditions. Alternatively, we propose a new treatment that promotes endothelial shear stress (ESS) enhancement using an intrapulmonary pulsatile catheter. Methods: Twelve piglets, divided in equal groups of 6: pulsatile (P) and non-pulsatile (NP), underwent permanent left anterior descending coronary artery ligation through sternotomy. After 1h of ischemia and heparin injection (150IU/kg): in P group, a pulsatile catheter was introduced into the pulmonary trunk and pulsated intermittently over 1h, and irrespective of heart rate (110bpm). In NP group, nitrates were given (7±2mg/kg/min) for 1h. Results: In P group all 6 animals survived ischemia for 120min, but in NP group only 2 animals survived. The 4 animals that died during the experiment in NP group survived for 93±14min. Hemodynamics and cardiac output (CO) were significantly improved in P group compared with NP group: CO was 0.92±0.15 vs. 0.52±0.08 in NP group (L/min; p<0.05), respectively. Vascular resistances (dynes.s.cm−5/kg) were significantly (p<0.05) lower in P group versus NP group: pulmonary resistance was 119±13 vs. 400±42 and systemic resistance was 319±43 vs. 1857±326, respectively. Myocardial apoptosis was significantly (p<0.01) lower in P group (0.66±0.07) vs. (4.18±0.27) in NP group. Myocardial endothelial NO synthase mRNA expression was significantly (p<0.01) greater in P group (0.90±0.09) vs. (0.25±0.04) in NP group. Conclusions: Intrapulmonary pulsatile catheter could improve hemodynamics and myocardial contractility in acute myocardial ischemia. This represents a cost-effective method, suitable for emergency setting as a first priority, regardless of classical coronary reperfusion. [ABSTRACT FROM AUTHOR]