Much attention has been focused recently on the relationship between h
omocysteinaemia and the development of premature atherosclerosis. Hype
rhomocysteinaemia constitutes as strong a risk factor for the developm
ent of the disease as either hypercholesterolaemia or smoking. Althoug
h the mechanism involved is unclear homocysteine exhibits prooxidative
activity in vitro. This finding suggests that it may be involved in t
he oxidative modification of low density lipoprotein (LDL). In the cur
rent study hyperhomocysteinaemia was induced in eight domestic pigs by
intermittent exposure to nitrous oxide for 4 weeks. At necropsy, card
iac tissue was removed and malondialdehyde (MDA) and the unsaturated f
atty acid content were measured and compared with values obtained from
air-breathing control animals. Nitrous oxide treated animals had sign
ificantly higher tissue concentrations of MDA than the controls. There
was also a reduction in the contribution of linoleic and linolenic ac
ids to the total fatty acid content of heart. The hyperhomocysteinaemi
c animals also had a significantly higher iron concentration in the he
art than controls. Hyperhomocysteinaemia was associated with elevation
s in tissue iron stores and increased in vivo lipid peroxidation. (C)
1997 Elsevier Science Ireland Ltd.