Cardiac structure and function in vitamin B-12-deprived rats.
The effect of prolonged vitamin B-12 deprivation in rats on the histological structure of heart and on cardiac linoleic acid oxidation has been investigated. Offspring from pregnant females fed vitamin B-12-deficient diets were fed the deprivation diet for up to 16 months, and the development of B-12 deficiency was monitored by determination of urinary methylmalonic acid levels. These levels averaged 4.2 mg/day by 9 months of B-12-deprivation diet, and 142 mg/day after 16 months. The hearts of these animals were characterized by extensive fibrosis, and electron microscopy revealed cardiac mitochondria that were grossly enlarged and distorted. The metabolic defect of B-12 deprivation in heart muscle was determined in isolated hearts during recirculating perfusion of labeled propionic acid. Both the uptake and oxidation of propionic acid were markedly reduced in hearts from B-12-deprived rats (16 months) compared with controls, and the site of the metabolic block, i.e., accumulation of labeled methylmalonate, was established. Vitamin B-12 deprivation did not affect the extraction of recirculating labeled linoleic acid by perfused hearts, in contrast to the effect on propionic extraction. Furthermore, the oxidation of the extracted fatty acid was markedly increased over controls. Analysis of the circulating media after 45-minute perfusions showed no accumulation of labeled methylmalonate but did contain significantly less succinate than perfusion media from control hearts. The results are discussed with respect to cardiac structure and to the oxidative pathway(s) for polyunsaturated fatty acids.
D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D008431:Maternal-Fetal Exchange; D008764:Methylmalonic Acid / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D010084:Oxidation-Reduction; D010477:Perfusion; D011247:Pregnancy; D011248:Pregnancy Complications; D051381:Rats; D014806:Vitamin B 12 Deficiency / Q000378:metabolism / Q000473:pathology
D005227:Fatty Acids; D008764:Methylmalonic Acid