[Comparative evaluation of the effects of carnitine stereoisomers and racemate on the cardio- and hemodynamics of rats on a carnitine-deficient diet].
L-carnitine (L-beta-hydroxy-gamma-N,N,N-trimethylaminobutyric acid) is conditionally necessary for mitochondrial transport and metabolism of long-chain fatty acids, and thus for myocardial energetic metabolism. D-carnitine is not biologically active and might interfere with proper utilization of the L isomer, and so there are claims that the racemic mixture (DL-carnitine) should be avoided. The pharmacological effects of carnitine are stereospecific: L-carnitine was effective in various animal and clinical studies, while D- and DL-carnitine was found to be ineffective or even toxic to some cells and tissues, such as muscle cells and the myocardium. DL-carnitine caused symptoms of myasthenia and cardiac arrhythmias, which disappeared after L-carnitine administration. Therefore, the purposes of this work were (1) to study the effect of L-carnitine vs. that of D- and DL-stereoisomers on carnitine restoration rate in blood plasma of carnitine-deficient rats and (2) to evaluate the effect of stereoisomers and racemate of carnitine on the cardio- and hemodynamics of rats on carnitine-deficient diet. To induce carnitine deficiency, 60 rats were placed on a carnitine-deficient diet containing 1 g of N-trimethyl-hydrazine-3-propionate (mildronate) per a kilogram of the diet. The controls, 15 rats, received a basal control diet of the same duration. After 80 days, L-, D-, and DL-carnitine were administered in a dose of 200 mg/kg per os for 30 days, together with the carnitine-deficiency diet. To investigate the effect of L-, D-, and DL-carnitine on the abnormalities of the myocardial function of the carnitine-deficiency rats, various hemodynamic variables including left ventricular pressure, indices of contractility and relaxation, heart rate, systolic and diastolic blood pressure in response to volume loading test, adrenoreactivity test, and maximal isometric loading test, were measured. In this study, the carnitine-deficient diet with mildronate caused a substantial loss of carnitine in blood plasma by 56.49% (19.70 +/- 4.97 vs. 45.27 +/- 6.97 micromol/ 1, p < 0.001), which was accompanied by myocardial malfunctioning. After 30 days of L-carnitine administration, the plasma level of carnitine was significantly higher by an average of 118.55% (p < 0.001) compared with carnitine-deficient controls, while after administration of D- and DL-stereoisomers the carnitine content did not change or increased insignificantly. L-carnitine administration to carnitine-deficient rats led to normalization in myocardial function including indices of contractility and relaxation, systolic and diastolic blood pressure in response to volume loading test, adrenoreactivity test, and maximal isometric loading test. Chronic administration of D- and DL-carnitine did not change an altered cardio- and hemodynamics of carnitine-deficient rats compared with L-carnitine.
Spasov
A A
AA
Iezhitsa
I N
IN
Tiurenkov
I N
IN
Perfilova
V N
VN
Gurova
N A
NA
Kravchenko
M S
MS
D000818:Animals; D002331:Carnitine / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D007537:Isometric Contraction; D008297:Male; D051381:Rats; D013237:Stereoisomerism; D016277:Ventricular Function, Left / Q000187:drug effects
D002331:Carnitine