Skip to main content
Top
Published in: General Thoracic and Cardiovascular Surgery 5/2019

01-05-2019 | Original Article

Lanthanum carbonate, a phosphate binder, inhibits calcification of implanted aortic allografts in a rat model

Authors: Osamu Kinoshita, Haruo Yamauchi, Noboru Motomura, Minoru Ono

Published in: General Thoracic and Cardiovascular Surgery | Issue 5/2019

Login to get access

Abstract

Objectives

Calcification is one of the major postoperative problems after aortic allograft implantation. We hypothesized that phosphate binders, lanthanum carbonate and calcium carbonate inhibit calcification of implanted aortic allografts and verified this hypothesis using a rat model.

Methods

Aortas were harvested from 4-week-old Brown Norway rats and implanted into the subdermal space of 4-week-old Lewis rats. Twenty-seven recipient Lewis rats were divided into Group N, Group L, and Group C (9 rats per group), which were fed a normal diet, a normal diet containing 3% lanthanum carbonate, and a normal diet containing 3% calcium carbonate, respectively. Implanted aortic allografts were explanted 2 weeks later. Calcification of aortic allografts was evaluated using von Kossa staining and calcium content assay. Calcification score was defined in von Kossa staining as 0 (none), 1 (mild), 2 (moderate), and 3 (severe). Serum calcium and phosphorus levels at euthanasia were measured.

Results

Calcification scores were 2.6, 1.2, and 0.8, and calcium content was 48.9, 15.8, and 8.9 mg/dry·g, in Groups N, L, and C, respectively. Calcification was significantly reduced in Groups L and C. Serum calcium level was 11.5, 12.2, and 13.5 mg/dl, and serum phosphorus level was 15.4, 12.5, and 11.7 mg/dl, in Groups N, L, and C, respectively. Serum calcium level in Group C was significantly higher than in the other two groups.

Conclusions

Lanthanum carbonate and calcium carbonate significantly reduced calcification of implanted aortic allografts in young rats. Although calcium carbonate induced hypercalcemia, lanthanum carbonate has significant potential to inhibit calcification of implanted aortic allografts.
Literature
1.
go back to reference Yap CH, Yii M. Allograft aortic valve replacement in the adult: a review. Heart Lung Circ. 2004;13:41–51.CrossRefPubMed Yap CH, Yii M. Allograft aortic valve replacement in the adult: a review. Heart Lung Circ. 2004;13:41–51.CrossRefPubMed
2.
go back to reference Saito A, Motomura N, Kakimi K, Narui K, Noguchi N, Sasatsu M, et al. Vascular allografts are resistant to methicillin-resistant Staphylococcus aureus through indoleamine 2,3-dioxygenase in a murine model. J Thorac Cardiovasc Surg. 2008;136:159–67.CrossRefPubMed Saito A, Motomura N, Kakimi K, Narui K, Noguchi N, Sasatsu M, et al. Vascular allografts are resistant to methicillin-resistant Staphylococcus aureus through indoleamine 2,3-dioxygenase in a murine model. J Thorac Cardiovasc Surg. 2008;136:159–67.CrossRefPubMed
3.
go back to reference Dossche K, Brutel Riviere de la A, Morshuis W, Schepens M, Ernst J. Aortic root replacement with human tissue valves in aortic valve endocarditis. Eur J Cardiothorac Surg. 1997;12:47–55.CrossRefPubMed Dossche K, Brutel Riviere de la A, Morshuis W, Schepens M, Ernst J. Aortic root replacement with human tissue valves in aortic valve endocarditis. Eur J Cardiothorac Surg. 1997;12:47–55.CrossRefPubMed
4.
go back to reference Motomura N, Takamoto S, Murakawa T, Yoneda N, Shibusawa S, Maeda K, et al. Short-term result of aortic valve replacement with cryopreserved homograft valve in the University of Tokyo Tissue Bank. Artif Org. 2002;26:449–52.CrossRef Motomura N, Takamoto S, Murakawa T, Yoneda N, Shibusawa S, Maeda K, et al. Short-term result of aortic valve replacement with cryopreserved homograft valve in the University of Tokyo Tissue Bank. Artif Org. 2002;26:449–52.CrossRef
5.
go back to reference Kitamura T, Morota T, Motomura N, Ono M, Shibata K, Ueno K, et al. Management of infected grafts and aneurysms of the aorta. Ann Vasc Surg. 2005;19:335–42.CrossRefPubMed Kitamura T, Morota T, Motomura N, Ono M, Shibata K, Ueno K, et al. Management of infected grafts and aneurysms of the aorta. Ann Vasc Surg. 2005;19:335–42.CrossRefPubMed
6.
go back to reference Fontan F, Choussat A, Deville C, Doutremepuich C, Coupillaud J, Vosa C. Aortic valve homografts in the surgical treatment of complex cardiac malformations. J Thorac Cardiovasc Surg. 1984;87:649–57.PubMed Fontan F, Choussat A, Deville C, Doutremepuich C, Coupillaud J, Vosa C. Aortic valve homografts in the surgical treatment of complex cardiac malformations. J Thorac Cardiovasc Surg. 1984;87:649–57.PubMed
7.
go back to reference O’Brien MF, Harrocks S, Stafford EG, Gardner MA, Pohlner PG, Tesar PJ, et al. The homograft aortic valve: a 29-year, 99.3% follow up of 1022 valve replacements. J Heart Valve Dis. 2001;10:334–44. discussion 335.PubMed O’Brien MF, Harrocks S, Stafford EG, Gardner MA, Pohlner PG, Tesar PJ, et al. The homograft aortic valve: a 29-year, 99.3% follow up of 1022 valve replacements. J Heart Valve Dis. 2001;10:334–44. discussion 335.PubMed
8.
go back to reference Tweddell JS, Pelech AN, Frommelt PC, Mussatto KA, Wyman JD, Fedderly RT, et al. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation. 2000;102:III130–135.CrossRefPubMed Tweddell JS, Pelech AN, Frommelt PC, Mussatto KA, Wyman JD, Fedderly RT, et al. Factors affecting longevity of homograft valves used in right ventricular outflow tract reconstruction for congenital heart disease. Circulation. 2000;102:III130–135.CrossRefPubMed
9.
go back to reference Clarke DR, Campbell DN, Hayward AR, Bishop DA. Degeneration of aortic valve allografts in young recipients. J Thorac Cardiovasc Surg. 1993;105:934–41. discussion 941–932.PubMed Clarke DR, Campbell DN, Hayward AR, Bishop DA. Degeneration of aortic valve allografts in young recipients. J Thorac Cardiovasc Surg. 1993;105:934–41. discussion 941–932.PubMed
10.
go back to reference Yankah AC, Alexi-Meskhishvili V, Weng Y, Schorn K, Lange PE, Hetzer R. Accelerated degeneration of allografts in the first two years of life. Ann Thorac Surg. 1995;60:71–6. discussion 576–577.CrossRef Yankah AC, Alexi-Meskhishvili V, Weng Y, Schorn K, Lange PE, Hetzer R. Accelerated degeneration of allografts in the first two years of life. Ann Thorac Surg. 1995;60:71–6. discussion 576–577.CrossRef
11.
go back to reference Mitchell RN, Jonas RA, Schoen FJ. Pathology of explanted cryopreserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg. 1998;115:118–27.CrossRefPubMed Mitchell RN, Jonas RA, Schoen FJ. Pathology of explanted cryopreserved allograft heart valves: comparison with aortic valves from orthotopic heart transplants. J Thorac Cardiovasc Surg. 1998;115:118–27.CrossRefPubMed
12.
go back to reference Yamauchi H, Motomura N, Chung UI, Sata M, Takai D, Saito A, et al. Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model. J Thorac Cardiovasc Surg. 2013;145:522–30.CrossRefPubMed Yamauchi H, Motomura N, Chung UI, Sata M, Takai D, Saito A, et al. Growth-associated hyperphosphatemia in young recipients accelerates aortic allograft calcification in a rat model. J Thorac Cardiovasc Surg. 2013;145:522–30.CrossRefPubMed
14.
go back to reference Woda CB, Halaihel N, Wilson PV, Haramati A, Levi M, Mulroney SE. Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat. Am J Physiol Renal Physiol. 2004;287:F117–23.CrossRefPubMed Woda CB, Halaihel N, Wilson PV, Haramati A, Levi M, Mulroney SE. Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat. Am J Physiol Renal Physiol. 2004;287:F117–23.CrossRefPubMed
15.
go back to reference Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis. 1998;31:607–17.CrossRefPubMed Block GA, Hulbert-Shearon TE, Levin NW, Port FK. Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study. Am J Kidney Dis. 1998;31:607–17.CrossRefPubMed
16.
go back to reference Webb CL, Nguyen NM, Schoen FJ, Levy RJ. Calcification of allograft aortic wall in a rat subdermal model. Pathophysiology and inhibition by Al3 + and aminodiphosphonate preincubations. Am J Pathol. 1992;141:487–96.PubMedPubMedCentral Webb CL, Nguyen NM, Schoen FJ, Levy RJ. Calcification of allograft aortic wall in a rat subdermal model. Pathophysiology and inhibition by Al3 + and aminodiphosphonate preincubations. Am J Pathol. 1992;141:487–96.PubMedPubMedCentral
17.
go back to reference Shigematsu T. Lanthanum carbonate effectively controls serum phosphate without affecting serum calcium levels in patients undergoing hemodialysis. Ther Apher Dial. 2008;12:55–61.CrossRefPubMed Shigematsu T. Lanthanum carbonate effectively controls serum phosphate without affecting serum calcium levels in patients undergoing hemodialysis. Ther Apher Dial. 2008;12:55–61.CrossRefPubMed
18.
go back to reference Ben-Dov IZ, Pappo O, Sklair-Levy M, Galitzer H, Ilan Y, Naveh-Many T, et al. Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats. Nephrol Dial Transplant. 2007;22:362–8.CrossRefPubMed Ben-Dov IZ, Pappo O, Sklair-Levy M, Galitzer H, Ilan Y, Naveh-Many T, et al. Lanthanum carbonate decreases PTH gene expression with no hepatotoxicity in uraemic rats. Nephrol Dial Transplant. 2007;22:362–8.CrossRefPubMed
19.
20.
go back to reference Foley RN, Collins AJ, Ishani A, Kalra PA. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156:556–63.CrossRefPubMed Foley RN, Collins AJ, Ishani A, Kalra PA. Calcium-phosphate levels and cardiovascular disease in community-dwelling adults: the Atherosclerosis Risk in Communities (ARIC) Study. Am Heart J. 2008;156:556–63.CrossRefPubMed
21.
go back to reference Slatopolsky E, Weerts C, Stokes T, Windus D, Delmez J. Alternative phosphate binders in dialysis patients: calcium carbonate. Semin Nephrol. 1986;6:35–41.PubMed Slatopolsky E, Weerts C, Stokes T, Windus D, Delmez J. Alternative phosphate binders in dialysis patients: calcium carbonate. Semin Nephrol. 1986;6:35–41.PubMed
22.
go back to reference Damment SJ, Pennick M. Clinical pharmacokinetics of the phosphate binder lanthanum carbonate. Clin Pharmacokinet. 2008;47:553–63.CrossRefPubMed Damment SJ, Pennick M. Clinical pharmacokinetics of the phosphate binder lanthanum carbonate. Clin Pharmacokinet. 2008;47:553–63.CrossRefPubMed
23.
go back to reference Pennick M, Dennis K, Damment SJ. Absolute bioavailability and disposition of lanthanum in healthy human subjects administered lanthanum carbonate. J Clin Pharmacol. 2006;46:738–46.CrossRefPubMed Pennick M, Dennis K, Damment SJ. Absolute bioavailability and disposition of lanthanum in healthy human subjects administered lanthanum carbonate. J Clin Pharmacol. 2006;46:738–46.CrossRefPubMed
24.
go back to reference Damment SJ, Pennick M. Systemic lanthanum is excreted in the bile of rats. Toxicol Lett. 2007;171:69–77.CrossRefPubMed Damment SJ, Pennick M. Systemic lanthanum is excreted in the bile of rats. Toxicol Lett. 2007;171:69–77.CrossRefPubMed
25.
go back to reference Hutchison AJ, Barnett ME, Krause R, Siami GA. Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease Stage 5 receiving hemodialysis. Clin Nephrol. 2009;71:286–95.PubMed Hutchison AJ, Barnett ME, Krause R, Siami GA. Lanthanum carbonate treatment, for up to 6 years, is not associated with adverse effects on the liver in patients with chronic kidney disease Stage 5 receiving hemodialysis. Clin Nephrol. 2009;71:286–95.PubMed
26.
go back to reference Wills MR, Savory J. Aluminium poisoning: dialysis encephalopathy, osteomalacia, and anaemia. Lancet. 1983;2:29–34.CrossRefPubMed Wills MR, Savory J. Aluminium poisoning: dialysis encephalopathy, osteomalacia, and anaemia. Lancet. 1983;2:29–34.CrossRefPubMed
27.
go back to reference Altmann P, Barnett ME, Finn WF. Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int. 2007;71:252–9.CrossRefPubMed Altmann P, Barnett ME, Finn WF. Cognitive function in Stage 5 chronic kidney disease patients on hemodialysis: no adverse effects of lanthanum carbonate compared with standard phosphate-binder therapy. Kidney Int. 2007;71:252–9.CrossRefPubMed
28.
go back to reference D’Haese PC, Spasovski GB, Sikole A, Hutchison A, Freemont TJ, Sulkova S, et al., A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. 2003: S73–S78. D’Haese PC, Spasovski GB, Sikole A, Hutchison A, Freemont TJ, Sulkova S, et al., A multicenter study on the effects of lanthanum carbonate (Fosrenol) and calcium carbonate on renal bone disease in dialysis patients. Kidney Int. 2003: S73–S78.
29.
go back to reference Behets GJ, Dams G, Vercauteren SR, Damment SJ, Bouillon R, De Broe ME, et al. Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol. 2004;15:2219–28.CrossRefPubMed Behets GJ, Dams G, Vercauteren SR, Damment SJ, Bouillon R, De Broe ME, et al. Does the phosphate binder lanthanum carbonate affect bone in rats with chronic renal failure? J Am Soc Nephrol. 2004;15:2219–28.CrossRefPubMed
30.
go back to reference Feng L, Xiao H, He X, Li Z, Li F, Liu N, et al. Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett. 2006;165:112–20.CrossRefPubMed Feng L, Xiao H, He X, Li Z, Li F, Liu N, et al. Neurotoxicological consequence of long-term exposure to lanthanum. Toxicol Lett. 2006;165:112–20.CrossRefPubMed
Metadata
Title
Lanthanum carbonate, a phosphate binder, inhibits calcification of implanted aortic allografts in a rat model
Authors
Osamu Kinoshita
Haruo Yamauchi
Noboru Motomura
Minoru Ono
Publication date
01-05-2019
Publisher
Springer Singapore
Published in
General Thoracic and Cardiovascular Surgery / Issue 5/2019
Print ISSN: 1863-6705
Electronic ISSN: 1863-6713
DOI
https://doi.org/10.1007/s11748-018-1026-7

Other articles of this Issue 5/2019

General Thoracic and Cardiovascular Surgery 5/2019 Go to the issue