Tl. Broderick et al., L-PROPIONYLCARNITINE EFFECTS ON CARDIAC CARNITINE CONTENT AND FUNCTION IN SECONDARY CARNITINE DEFICIENCY, Canadian journal of physiology and pharmacology, 73(4), 1995, pp. 509-514
Long-term treatment with sodium pivalate, a compound conjugated to car
nitine and excreted in the urine, results in carnitine deficiency and
Cardiac dysfunction. Since L-propionylcarnitine (LPC) is generally of
benefit to cardiac function, it was of interest to determine whether i
t is effective in preventing the reductions in both heart carnitine co
ntent and function from occurring in carnitine deficiency. Secondary c
arnitine deficiency was induced in male Sprague-Dawley rats by supplem
enting the drinking water with 20 mM sodium pivalate for 26 weeks. Con
trol animals received an equimolar concentration of sodium bicarbonate
. At 13 weeks into treatment, a subgroup of control and sodium pivalat
e animals were given 80 mg/kg of LPC in their drinking water. Followin
g treatment, isolated working hearts were perfused with buffer contain
ing 11 mM glucose and 0.4 mM palmitate. Hearts from sodium pivalate tr
eated animals demonstrated a severe reduction in tissue carnitine. Whe
n mechanical function was measured in these hearts, heart rate, rate-p
ressure product, and aortic flow were significantly depressed. Treatme
nt with LPC, however, prevented the depletion in cardiac carnitine con
tent and improved these cardiac parameters. Our results demonstrate th
at LPC treatment is beneficial in preventing the depression in cardiac
function from occurring in this model of secondary carnitine deficien
cy.