Cardiac Metabolism in Thiamin Deficiency in Rats

Abstract

Prior studies have suggested that the cardiac dysfunction of thiamin deficiency may be due partly to decreased pyruvate decarboxylation with subsequent impairment of Krebs cycle activity in the heart and decreased synthesis of ATP for cardiac work. Increased catecholamine and acetylcholine concentrations have also been described in thiamin-deficient heart and it has been suggested that they may be cardiotoxic. This study assessed directly the effect of progressive thiamin deficiency and its reversal on cardiac ATP stores and correlated these findings with pyruvate metabolism in the heart. Cardiac catecholamines and acetylcholine were also measured, controlling for the effect of inanition and employing a specific acetylcholine assay. Rats with diet-induced thiamin deficiency developed encephalopathy and significant cardiac hypertrophy at 5 weeks. The encephalopathy reversed fully within 24 hours with 25 μg of thiamin. Cardiac ATP in thiamin-deficient rats was normal at 2 and 3 weeks but fell by 16.8 and 34.1% (P < 0.01) below pair-fed control values at 4 and 5 weeks. This fall in cardiac ATP correlated well with a progressive and substantial decrease in pyruvate decarboxylase activity and with the accumulation of pyruvate in the heart, but not with cardiac transketolase activity. Cardiac anaerobic glycolytic rate and ATP utilization were normal in these thiamin-deficient rats. At 24 and 72 hours after thiamin administration, cardiac pyruvate decarboxylase activity rose progressively and sharply, heart pyruvate fell toward normal and ATP reverted to normal. Heart transketolase, however, rose only slightly and cardiac hypertrophy persisted. Auricular catecholamine concentration in thiamin-deficient symptomatic rats was increased by 25.7% (P < 0.03) but whole heart catecholamines and acetylcholine in these animals were similar to pair-fed control values. Inanition alone significantly raised cardiac catecholamines. These composite data indicate that: 1) Thiamin deficiency induces cardiac hypertrophy and a reversible depletion of heart ATP which correlates well with “entry” of pyruvate into the Krebs cycle, suggesting that the decreased ATP concentration observed is the result of its impaired synthesis in the thiamin-deficient heart. 2) Thiamin deficiency induces a small increase in the cardiac auricular catecholamine concentration, whereas whole heart catecholamines and acetylcholine are not altered by thiamin depletion.