This Article Order Full text via Infotrieve Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Webb, C. L. Articles by Levy, R. J. Search for Related Content PubMed PubMed Citation Articles by Webb, C. L. Articles by Levy, R. J.

American Journal of Pathology, Vol 138, 971-981, Copyright © 1991 by American Society for Investigative Pathology

REGULAR ARTICLES

Inhibition of mineralization of glutaraldehyde-pretreated bovine pericardium by AlCl3. Mechanisms and comparisons with FeCl3, LaCl3, and Ga(NO3)3 in rat subdermal model studies

CL Webb, FJ Schoen, WE Flowers, AC Alfrey, C Horton and RJ Levy
Section of Pediatric Cardiology, Department of Pediatrics, University of Michigan Medical Center, Ann Arbor 48109-0576.

In the present study, the authors investigated the mechanism by which Al3+ preincubations inhibited the pathologic calcification of glutaraldehyde-pretreated bovine pericardium (GPBP) implanted subdermally in rats. The concentration dependency of the Al3+ anticalcification effect was compared with that of other trivalent metal ions (Fe3+, Ga3+, La3+) known to interact with calcium phosphates. In vitro incubations of GPBP were carried out in AlCl3 (10(- 3) mol/l [molar] to 10(-1) mol/l) to ascertain both the optimal conditions for uptake of Al3+ and the time course of Al3+ dissociation. Al3+ uptake by GPBP was concentration dependent and occurred rapidly, with tissue levels after 1 hour not differing significantly from those after 72 hours of incubation. Analyses of GPBP samples preincubated in AlCl3 (0.1 mol/l, 24 hours) showed that more than 75% of the Al3+ remained tightly bound after 60 days' in vitro release at 37 degrees C, pH 7.4. Preincubations of GPBP in AlCl3 significantly inhibited calcification after subdermal implantation in rats for 60 days (Ca++ = 5.1 +/- 0.9 microgram/mg, 11.5 +/- 4.6 micrograms/mg, 70.3 +/- 23.0 micrograms/mg, mean +/- standard error [SE], for 10(-1) mol/l, 10(-2) mol/l, 10(-3) mol/l AlCl3, respectively), compared with controls (Ca++ = 110.0 +/- 9.3 micrograms/mg). All animals were free of Al3(+)- mediated adverse effects on bone, as determined by light microscopic evaluation of femoral epiphyseal growth plates. Transmission electron microscopy coupled with electron energy loss spectroscopy (EELS) of GPBP incubated in 10(-1) mol l AlCl3 for 24 hours demonstrated discrete Al3+ localization in the sarcolemma and cytoplasmic and nuclear membranes of devitalized pericardial connective tissue cells at intracellular sites coincident with phosphorus loci. Similar intracellular localization remained prominent in explants removed after 60 days; no calcific deposits were noted in these specimens. Preincubations in Fe3+ but not Ga3+ and La3+ solutions yielded significant inhibition of GPBP calcification, which did not differ significantly from that provided by Al3- and had a comparable concentration dependency. Light microscopic examination (Prussian blue staining) and EELS of FeCl3-preincubated explants demonstrated Fe3+ localization within devitalized GPBP connective tissue cells. The authors conclude that Al3+ and Fe3+ significantly inhibit the pathologic mineralization of glutaraldehyde-pretreated bovine pericardium by mechanisms that are likely related to the high affinity of these cations for membrane associated and other intracellular phosphorus loci.

This article has been cited by other articles:

				N. D. Desai and G. T. Christakis Bioprosthetic Aortic Valve Replacement: Stented Pericardial and Porcine Valves Card. Surg. Adult, January 1, 2008; 3(2008): 857 - 894. [Full Text]

				E. Rieder, G. Seebacher, M.-T. Kasimir, E. Eichmair, B. Winter, B. Dekan, E. Wolner, P. Simon, and G. Weigel Tissue Engineering of Heart Valves: Decellularized Porcine and Human Valve Scaffolds Differ Importantly in Residual Potential to Attract Monocytic Cells Circulation, May 31, 2005; 111(21): 2792 - 2797. [Abstract] [Full Text] [PDF]

				J. N. Clark, M. F. Ogle, P. Ashworth, R. W. Bianco, and R. J. Levy Prevention of Calcification of Bioprosthetic Heart Valve Cusp and Aortic Wall With Ethanol and Aluminum Chloride Ann. Thorac. Surg., March 1, 2005; 79(3): 897 - 904. [Abstract] [Full Text] [PDF]

				F. J. Schoen and R. J. Levy Calcification of Tissue Heart Valve Substitutes: Progress Toward Understanding and Prevention Ann. Thorac. Surg., March 1, 2005; 79(3): 1072 - 1080. [Abstract] [Full Text] [PDF]

				N. D. Desai and G. T. Christakis Stented Mechanical/Bioprosthetic Aortic Valve Replacement Card. Surg. Adult, January 1, 2003; 2(2003): 825 - 856. [Full Text]

				M. Bailey, H. Xiao, M. Ogle, and N. Vyavahare Aluminum Chloride Pretreatment of Elastin Inhibits Elastolysis by Matrix Metalloproteinases and Leads to Inhibition of Elastin-Oriented Calcification Am. J. Pathol., December 1, 2001; 159(6): 1981 - 1986. [Abstract] [Full Text] [PDF]

				S. C. Vasudev, T. Chandy, M. Mohanty, U. P. R., and C. P. Sharma Inhibition of Bioprosthesis Calcification Due to Synergistic Effect of Fe/Mg Ions to Polyethylene Glycol Grafted Bovine Pericardium J Biomater Appl, October 1, 2001; 16(2): 93 - 107. [Abstract] [PDF]

				N. Vyavahare, M. Ogle, F. J. Schoen, and R. J. Levy Elastin Calcification and its Prevention with Aluminum Chloride Pretreatment Am. J. Pathol., September 1, 1999; 155(3): 973 - 982. [Abstract] [Full Text] [PDF]

				F. J. Schoen, D. Hirsch, R. W. Bianco, and R. J. Levy Onset and progression of calcification in porcine aortic bioprosthetic valves implanted as orthotopic mitral valve replacements in juvenile sheep J. Thorac. Cardiovasc. Surg., November 1, 1994; 108(5): 880 - 887. [Abstract] [Full Text]

				F.J. Schoen and R.J. Levy Heart valve bioprostheses: antimineralization Eur. J. Cardiothorac. Surg., January 1, 1992; 6(suppl_1): S91 - S94. [Abstract] [PDF]