Experimental hypervitaminosis D was produced in cows by the daily feeding of 30 million U.S.P. units of vitamin D for varying periods of time. Cardiovascular mineralization was not present after 7 days, but was observed after 10 days and became extensive and widespread after 21 and 30 days. Pregnant cows developed more severe lesions than non-pregnant ones.
In the heart, the lesions were more severe on the left side, and consisted of subendocardial mineralization and hemorrhage. In the elastic arteries, the degree of mineralization was maximal proximally, and diminished in severity distally. In the muscular arteries, the mineral deposits when confined to the media were accompanied by a proliferative intimal reaction. The veins were less severely affected than the arteries.
Histochemically the mineral deposits contained abundant calcium and phosphorus. X-ray diffraction studies indicated the principal inorganic product of the vitamin D-induced mineralization was a carbonate hydroxyapatite, comparable in crystallochemical characteristics to that of bone.
BlackburnP.S.BlaxterK.L.CastleE.J.:
Vitamin D3 toxicity in calves.
Proc. Nutr. Soc.16:
16
(1957).
3.
CapenC.C.ColeC.R.HibbsJ.W.WagnerA.R.:
Bioassay and quantitative morphologic analysis of the parathyroid glands, and serum and urine changes of cows fed high levels of vitamin D.
Amer. J. vet. Res.Accepted for publication
(1966).
4.
CapenC.C.KoestnerA.ColeC.R.:
The ultrastructure and histochemistry of normal parathyroid glands of pregnant and nonpregnant cows.
Lab. Invest.14:
1673–1690,
(1965).
5.
CapenC.C.KoestnerA.ColeC.R.:
The ultrastructure, histopathology and histochemistry of the parathyroid glands of pregnant and nonpregnant cows fed a high level of vitamin D.
Lab. Invest.14:
1809–1825,
(1965).
6.
ClarkI.SmithM.R.:
Effects of hypervitaminosis A and D on skeletal metabolism.
J. biol. Chem.239:
1266–1271,
(1964).
7.
ColeC.R.ChamberlainD.M.HibbsJ.W.PoundenW.D.SmithC.R.:
Vitamin D (viosterol) poisoning in a cow, from a study on the prevention of parturient paresis.
J. amer. vet. med. Ass.130:
298–299,
(1957).
8.
CollazoJ.A.RubinoP.VarelaP.:
Knochenbildung und Wachstumssörung bei der Hypervitaminosis D.
Virchows Arch.274:
281–293,
(1930).
9.
ConradH.R.HansardS.L.:
Effects of massive doses of vitamin D on physiological behavior of calcium in cattle.
J. appl. Physiol.10:
98–102,
(1957).
10.
ConradH.R.HansardS.L.HibbsJ.W.:
Studies on milk fever in dairy cows. V. The effect of massive oral doses of vitamin D on absorption, excretion, retention and blood levels of calcium and phosphorus.
J. Dairy Sci.39:
1697–1705,
(1956).
11.
EisensteinR.GroffW.A.:
Experimental hypervitaminosis D, hypercalcemia, hypermucoproteinemia and metastatic calcification.
Proc. Soc. exp. Biol. Med.94:
441–444,
(1957).
EisensteinR.AyerJ.P.PapajiannisS.HassG.M.EllisH.:
Mineral binding by human arterial elastic tissue.
Lab. Invest.13:
1198–1204,
(1964).
14.
FollisR.H.Jr.:
Studies on hypervitaminosis D.
Amer. J. Path.31:
568–569,
(1955).
15.
GiacomelliF.SpiroD.WienerJ.:
A study of metastatic renal calcification at the cellular level.
J. Cell Biol.22:
189–206,
(1964).
16.
GlimcherM.J.BonarL.C.DanielE.J.:
The molecular structure of the protein matrix of bovine dental enamel.
J. mol. Biol.3:
541–546,
(1961).
17.
GoormaghtighN.HandovskyH.:
Effect of vitamin D2 (calciferol) on the dog.
Arch. Path.26:
1144–1182,
(1938).
18.
GreigA.:
Massive doses of vitamin D.
Vet. Rec.75:
981
(1963).
19.
GrossL.AntopolW.SacksB.:
A standardized procedure suggested for microscopic studies on the heart with observations on rheumatic hearts.
Arch. Path.10:
840–852,
(1930).
20.
HamA.W.LewisM.D.:
Hypervitaminosis D rickets, the action of vitamin D.
Brit. J. exp. Path.15:
228–234,
(1934).
21.
HassG.M.TrueheartR.E.HemmensA.:
Experimental atherosclerosis due to hypervitaminosis D.
Amer. J. Path.37:
521–549,
(1960).
22.
HassG.M.TrueheartR.E.TaylorC.B.StumpeM.:
An experimental histologic study of hypervitaminosis D.
Amer. J. Path.34:
395–431,
(1958).
23.
HibbsJ.W.ConradH.R.:
Studies of milk fever in dairy cows. VI. Effect of three prepartal dosage levels of vitamin D on milk fever incidence.
J. Dairy Sci.43:
1124–1129,
(1960).
24.
HibbsJ.W.PoundenW.D.:
Studies on milk fever in dairy cows. IV. Prevention by short-time, prepartum feeding of massive doses of vitaminD. J. Dairy Sci.38:
65–72
(1955).
25.
KentS.P.VawterG.F.DowbenR.M.BensonR.E.KentS.P.VawterG.F.DowbenR.M.BensonR.E.:
Hypervitaminosis D in monkeys. A clinical and pathologic study.
Amer. J. Path.34:
37–60
(1958).
26.
KreitmairH.MollT.:
Hypervitaminose durch grosse Dosen Vitamin D.
Münch. med. Wschr.75:
637–639,
(1928).
27.
LansingA.I.AlexM.RosenthalT.B.:
Calcium and elastin in human arterio-sclerosis.
J. Geront.5:
112–119,
(1950).
28.
ManstonR.PayneJ.M.:
Mineral imbalance in pregnant “milk-feverprone” cows and the value and possible toxic effects of treatment with vitamin D3 and dihydrotachysterol.
Brit. vet. J.120:
167–177,
(1964).
29.
MartinR.G.SchiffmanE.BlandenA.NylenM.:
Chemical and morphologic studies on the in vitro calcification of aorta.
J. cell. Biol.16:
243–252,
(1963).
30.
McConnellD.:
The crystal structure of bone.
Clin. Orthop.23:
253–268,
(1962).
31.
McConnellD.:
Crystal chemistry of hydroxyapatite. Its relation to bone mineral.
Arch. oral Biol.10:
421–431,
(1965).
32.
MulliganR.M.:
Metastatic calcification produced in dogs by hypervitaminosis D and haliphagia.
Amer. J. Path.23:
912
(1947).
33.
NeumanW. F.NeumanM. W.:
The Chemical Dynamics of Bone Mineral.
(University of Chicago Press,
Chicago1958).
34.
PayneJ.M.:
The danger of using massive doses of vitamin D3 in the prevention of milk fever.
Vet. Rec.75:
848–849,
(1963).
35.
PayneJ. M.:
Recent advances in our knowledge of milk fever.
Vet. Rec.76:
1275–1282,
(1965).
36.
ScarpelliD.:
Experimental nephrocalcinosis. A biochemical and morphologic study.
Lab. Invest.14:
123–141,
(1965).
37.
ScarpelliD.G.TremblayG.PearseA.G.E.:
A comparative cytochemical and cytologic study of vitamin D induced nephrocalcinosis.
Amer. J. Path.36:
331–353,
(1960).
38.
SchiffmannE.MartinG. R.CorcoranB.A.:
The role of the matrix in aortic calcification.
Arch. Biochem. Biophys.107:
284–291,
(1964).
39.
SchmidtmannM.:
Die durch Vigantol im Tierexperiment erzeugbaren Knochenveränderungen.
Virchows Arch.280:
1–17,
(1931).
40.
SeeklesL.WilsonJ.H.G.Philips-DupharN.V.:
Is the use of massive doses of vitamin D (Duphafral D3-1000) dangerous.
Vet. Rec.76:
486–487,
(1964).
41.
SeeklesL.ReitsmaP.DeManTh. J.WilsonJ.H.G.:
Resultatan van de Tijdige Intraveneuze Toediening van Hoge Doseringen Kristallijn Vitamin D3 in Gesolubiliseerde vorm aan Rundvee ter Voorkoming van Melkziekte.
Tijdschr. Diergeneesk.83:
125–136,
(1958).
42.
ShohlA.T.GoldblattH.BrownH.B.:
The pathologic effects upon rats of excess irradiated ergosterol.
J. clin. Invest.8:
505–531,
(1930).
43.
SmithC.R.:
Unpublished data.
44.
StoreyE.:
Osteosclerosis after intermittent administration of large doses of vitamin D in the rat. A note on the pathogenesis of osteopetrosis.
J. Bone Joint Surg.42:
606–625,
(1960).
45.
StrebelR.F.PayanH.HouseE.L.PanskyH.BarathM.:
Sex differences in a progeria-like syndrome.
Proc. Soc. exp. Biol. Med.117:
583–586,
(1964).
46.
SwanJ.B.:
The toxic effects of massive doses of calciferol on dairy cattle.
New Zeald. vet. J.1:
25–27,
(1952).
47.
TuttJ.B.:
Report on a clinical trial of Duphafral D3-1000 for the prevention of hypocalcemia in dairy cows.
Vet. Rec.75:
469–470,
(1963).
48.
UristM.R.:
Recent advances in the physiology of calcification.
J. Hone Joint Surg.46 A:
889–900
(1964).
49.
YuS.Y.BlumenthalH.T.:
The calcification of elastic fibers. I. Biochemical studies.
J. Geront.18:
119–126,
(1963).
50.
YuS.Y.BlumenthalH.T.:
The calcification of elastic fiber. III. Various crystalline structures of apatite in human aortae.
Lab. Invest.12:
1154–1162,
(1963).
