Calcification of allograft aortic wall in a rat subdermal model. Pathophysiology and inhibition by Al3+ and aminodiphosphonate preincubations.
Aortic allograft conduits and valves frequently undergo calcific degeneration. To study this problem, a rat subdermal model of nonvalved aortic wall allograft calcification was characterized, and experimental studies were carried out to test the hypothesis that aortic allograft preincubation in either amino-propanehydroxydiphosphonate (APDP) or AlCl3 would inhibit calcification in a rat subdermal model. Fresh thoracic aortas were harvested under sterile conditions from male Sprague-Dawley rats (350-400 g). APDP aortas were preincubated immediately in either 4 x 10(-3) mol/l, 4 x 10(-4) mol/l, or 4 x 10(-5) mol/l [14C] APDP (37 degrees C, pH 7.4) and controls were incubated in 0.05 mol/l HEPES buffer (pH 7.4, 37 degrees C, 30 min). Al3+ aortas were preincubated in either 10(-1) mol/l, 10(-2) mol/l, or 10(-3) mol/l AlCl3. Pretreated aortas were next implanted subdermally in weanling rats (3-week-old, male, Sprague-Dawley, 50-60 g) and retrieved after 21 days. Control explants retrieved at intervals up to 21 days demonstrated progressive calcification with bulk aortic allograft Ca2+ levels increasing from a preimplant value of 0.8 +/- 0.1 micrograms/mg to 129.8 +/- 12.9 micrograms/mg by 21 days. Light microscopy revealed that much of the calcium deposition was associated with elastin. Calcification was significantly inhibited in the 4 x 10(-3) mol/l and 4 x 10(-4) mol/l APDP preincubated groups was observed (Ca2+ = 0.70 +/- 0.15 micrograms/mg, 36.6 +/- 19.8 micrograms/mg, respectively versus 117.2 +/- 24.3 micrograms/mg, control). Inhibition of calcification in the groups preincubated in the two most concentrated AlCl3 solutions (Ca2+ = 13.9 +/- 4.9 micrograms/mg [10(-2) mol/l AlCl3], 36.6 +/- 7.1 micrograms/mg [10(-3) mol/l AlCl3], 171.0 +/- 13.2 micrograms/mg [control]) was also demonstrated. No adverse effects of either pretreatment, APDP, or AlCl3 were noted on bone or overall somatic growth.
Webb
C L
CL
Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor 48109-0576.
Nguyen
N M
NM
Schoen
F J
FJ
Levy
R J
RJ
D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001011:Aorta / Q000637:transplantation*; D001018:Aortic Diseases / Q000473:pathology* / Q000517:prevention & control; D002114:Calcinosis / Q000473:pathology* / Q000517:prevention & control; D002712:Chlorides / Q000494:pharmacology*; D004164:Diphosphonates / Q000494:pharmacology*; D008297:Male; D000077268:Pamidronate; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin; D014184:Transplantation, Homologous
D017607:Aluminum Compounds; D002712:Chlorides; D004164:Diphosphonates; D000077410:Aluminum Chloride; D000535:Aluminum; D000077268:Pamidronate