Summary
Rabbits were reared in utero and post partum under hypocupremic conditions (the diet containing only 0.60 p.p.m. copper). A control series was investigated as well. For the post partum series of rabbits the experiments lasted 2 months. At the end of the 7 th week petechial hemorrhages were observed in the ears. Angiography was carried out and cervical and head vessels were studied. Some vessel dilatations and unevennesses were observed. One animal died of heart rupture and another collapsed as a consequence of intramural bleeding in the ventricular wall. Within about two months all the animals were killed and autopsied. Intestinal bleedings were observed. A cystlike structure was found in a kidney of one hypocupremic rabbit. This finding may have been coincidental. The hearts and cervical and basal cerebral vessels were investigated by light and electron microscopy. Fibroblast accumulation, dissecting hemorrhages and defects or breaks in muscular and elastic tissue were observed. At the sites of fibrosis, accumulation of a neutral red-positive material was found. At the ultrastructural level lipids could be identified.
Deprivation of dietary copper thus resulted in changes of the heart and muscularis and elastica layers of cervical and basal cerebral vessels of rabbits.
Zusammenfassung
Kaninchen wurden in utero und post partum unter Entzug von Kupfer aus der Nahrung aufgezogen (die Nahrung enthielt nur 0,60 p.p.m. Kupfer). Eine Gruppe von Kontrolltieren wurde ebenfalls untersucht. Bei der post partum-Gruppe der Kaninchen dauerten die Versuche 2 Monate. Am Ende der 7. Woche wurden petechiale Blutungen in den Ohren beobachtet. Angiographisch wurden Gefäße des Kopfes und Nackens untersucht. Einige Dilatationen und Ungleichheiten wurden beobachtet. Bei zwei Tieren wurden Herzrisse festgestellt. Innerhalb von 2 Monaten wurden alle Tiere getötet und seziert. Es wurden Darmblutungen festgestellt. In der linken Niere einer der kupferarmen Kaninchen wurde eine cystenartige Bildung gefunden. Dieser Befund mag ein zufälliger gewesen sein. Das Herz, Cervicalgefäße und basale Hirngefäße wurden licht- und elektronenmikroskopisch untersucht. Anhäufungen von Fibroblasten, dissektive Blutungen und Defekte oder Brüche in Muskel- und elastischen Geweben wurden beobachtet. An den fibrösen Stellen wurde eine Anhäufung von neutral-rotem Material gefunden. Die Folgen des Entzugs von Kupfer aus der Nahrung waren somit Veränderungen des Herzens, muskulärer und elastischer Schichten der Cervicalgefäße und basalen Hirngefäße.
Similar content being viewed by others
References
Alpers, B. J.: Aneurysms of the circle of Willis. Morphological and clinical considerations. In:W. S. Fields, andA. L. Sahs (Eds.) Intracranial aneurysms and subarachnoid hemorrhage. Springfield, Ill.: Ch. C. Thomas 1965.
Baker, A. B., andJ. A. Resch: An approach to the etiologic mechanisms in cerebral atherosclerosis, 168–173. In:Millikan, C. H., R. G. Siekert, andJ. P. Whisnant (Eds). Cerebral vascular diseases. New York-London: Grune & Stratton 1965.
Glynn, L. E.: Medial defects in the circle of Willis and their relation to aneurysm formation. J. Path. Bact.51, 213–222 (1940).
Griffiths, D. E., andD. C. Wharton: Studies of the electron transport system. XXXV. Purification and properties of cytochrome oxidase. J. biol. Chem.236, 1850–1856 (1961a).
—— Studies of the electron transport system. XXXVI. Properties of copper in cytochrome oxidase. J. biol. Chem.236, 1857–1862 (1961b).
Hassler, O.: Morphological studies on the large cerebral arteries with reference to the aetiology of subarachnoid haemorrhage. Acta psychiat. scand. suppl. 154 (1961).
Jeppsson, P. G., andT. Olin: Cerebral angiography in the rabbit. An investigation of vascular anatomy and variation in circulatory pattern with conditions of injection. Lunds Universitets Årsskrift56, 14 (1960).
Maier, N., andH. Haimovici: Oxidative activity of aortic tissue of man, the rabbit and the dog with special reference to succinic dehydrogenase and cytochrome oxidase. Amer. J. Physiol.195, 476–480 (1958).
Mollier, D.: Quadruple stain (for connective tissue). In: Blakiston's New Medical Dictionary. The Blakiston Co., Philadelphia 1949, and in: Manual of histologic and special staining technics. Armed Forces Inst. Pathol., Washington D.C., 1957.
Mutlu, N., R. G. Berry, andB. J. Alpers: Massive cerebral hemorrhage. Arch. Neurol. (Chic.)8, 644–441 (1963).
Nyström, S. H. M.: Cytological aspects of the pathogenesis of intracranial aneurysms. In:W. S. Fields andA. L. Sahs. Intracranial aneurysms and subarachnoid hemorrhage. Springfield, Ill.: Ch. C. Thomas 1965.
O'Dell, B. L., B. C. Hardwick, G. Reynolds, andJ. E. Savage: Connective tissue defect in the chick resulting from copper deficiency. Proc. Soc. exp. Biol. (N. Y.)108, 402–405 (1961).
Reigh, E. E., andL. J. Lemmen: Cerebral aneurysms with intracranial pathology. J. Neurosurg.17, 469–476 (1960).
Savage, J. E., D. A. Ross, G. Reynolds, andB. L. O'Dell: Copper deficiency and beta-amino-proprionitrile toxicity in turkeys (abstract). Fed. Proc.21, 311 (1962).
Shields, G. S., W. F. Coulson, D. A. Kimball, W. H. Carnes, G. E. Cartwright, andM. M. Wintrobe: Studies on copper metabolism. XXXII. Cardiovascular lesions in copper-deficient swine. Amer. J. Path.41, 603–617 (1962).
Weissman, N., G. S. Shields, andW. H. Carnes: Cardiovascular studies on copper-deficient swine. IV. Content and solubility of the aortic elastin, collagen and hexosamine. J. biol. Chem.238, 3115–3118 (1963).
White, J. C., G. P. Sayre, andJ. P. Whisnant: Experimental destruction of the media for the production of intracranial arterial aneurysms. J. Neurosurg.18, 741–745 (1961).
Wilson, G., H. E. Riggs, andC. Rupp: The pathologic anatomy of ruptured cerebral aneurysms. J. Neurosurg.11, 128–134 (1954).
Author information
Authors and Affiliations
Additional information
These studies have been supported by the National Institutes of Health, United States Public Health Service Grant NB 5406 and by a grant from the Finska Läkaresällskapets fonder.
Rights and permissions
About this article
Cite this article
Nyström, S.H.M. Studies of the effect of experimental hypocupremia on the rabbit circulatory system, with special reference to the vessels of the neck and the base of the brain. Acta Neuropathol 10, 209–217 (1968). https://doi.org/10.1007/BF00687724
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00687724