ABSTRACT
31P-NMR in vivo spectroscopy is a non-invasive and non-hazardous technique which investigates chemical composition and metabolism of living objects, for example by determining phosphocreatine (PCr) and ATP concentrations. In the present study we investigated the influence of L-carnitine, acetyl-L-carnitine and propionyl-L-carnitine on the energetic state of the Langendorff rat heart subjected to an ischemic period of 20 min followed by a reperfusion period of 60 min. To avoid an overlapping of the effects of fatty acids and glucose, the hearts were perfused with a Tyrode solution containing no fatty acids. Ischemia causes a rapid decrease in the PCr signal, followed by a decrease in the ATP signal after a prolonged period of ischemia. At the same time, a drastic increase in the Pi signal was observed. A partial recovery of the ATP and PCr signals was observed in the reperfusion period. With L-carnitine a markedly improved recovery of the high energy phosphates (e.g. increased PCr/P ratios) was found. With acetyl-L-carnitine this effect was enhanced in the first postischemic phase. It was followed, however, by a more rapid decrease in the PCr/Pi ratio in the late reperfusion period. The effect of propionyl-L-carnitine was not significantly improved in the first minutes of the reperfusion period, but during the whole reperfusion phase a stabilization of the PCr/Pi ratio was observed. Intracellular pH can be calculated from determination of the Pi-chemical shift. This shows that L-carnitine and its derivatives have a protective effect against intracellular pH decrease during ischemia. L-carnitine improves the energetic state of the heart, which leads to increased ischemia tolerance. Hearts under L-carnitine were able to tolerate up to four ischemia-reperfusion periods in succession, whereas the controls were not able to do so. These NMR results confirm the hypothesis that L-carnitine and its esters have a protective effect in the reperfusion period of the ischemic rat heart. This could be of importance for the treatment of ischemic cardiac diseases.
Subject(s)
Adenosine Triphosphate/metabolism , Carnitine/analogs & derivatives , Carnitine/pharmacology , Heart/drug effects , Myocardium/metabolism , Phosphocreatine/metabolism , Acetylcarnitine/pharmacology , Animals , Energy Metabolism , Female , In Vitro Techniques , Magnetic Resonance Spectroscopy , Myocardial Ischemia/metabolism , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/metabolism , Perfusion , Phosphates/metabolism , Rats , Rats, WistarABSTRACT
31P-NMR spectroscopy is a method for continuous, noninvasive determination of high-energy phosphates in the intact organ. On the isolated Langendorff perfused rat heart the effect of L-carnitine on concentration of cytosolic ATP and phosphocreatine was studied under influence of a single or repeated periods of 20 min ischemia. On reperfusion the carnitine-treated hearts showed higher CP/Pi values and an increase of the energy index (CP + ATP)/(C) + ATP + Pi) then did control hearts. An improved ischemia tolerance was demonstrated.
