Shug A, Paulson D, Subramanian R, Regitz V
University of Wisconsin Medical School, Madison.
Cardiovasc Drugs Ther. 1991 Feb;5 Suppl 1:77-83. doi: 10.1007/BF00128246.
When cardiac function in isolated rat hearts was impaired by subjecting them to ischemia, subsequent perfusion with propionyl-L-carnitine and related compounds increased their rate of recovery. Thus at 11 mM, both propionyl-L-carnitine and, to a lesser extent, its taurine amide, and also acetyl-L-carnitine, significantly restored cardiac function in 15 minutes after 90 minutes of either low-flow or intermittent no-flow ischemia. Carnitine itself was ineffective. Propionyl-L-carnitine also increased tissue ATP and creatine phosphate compared with controls, but did not affect the levels of long-chain acyl carnitine and coenzyme. These esters also depleted fatty acid peroxidation, as shown with malonaldehyde, and were more effective than carnitine in preventing the production of superoxide. In myocytes, propionyl-L-carnitine alone stimulated palmitate oxidation, but in rat heart homogenates, both L-carnitine and propionyl-L-carnitine did so, while acetyl-L-carnitine was actually inhibitory. Possible mechanisms for the protective action of propionyl-L-carnitine against ischemia include an increased rate of cellular transport, stimulation of fatty acid oxidation, and a reduction of free radical formation.
当通过使离体大鼠心脏缺血来损害其心脏功能时,随后用丙酰-L-肉碱及相关化合物进行灌注,可提高其恢复速率。因此,在11 mM浓度下,丙酰-L-肉碱及其牛磺酸酰胺(程度稍低)以及乙酰-L-肉碱,在低流量或间歇性无流量缺血90分钟后的15分钟内,均能显著恢复心脏功能。肉碱本身则无效。与对照组相比,丙酰-L-肉碱还能增加组织ATP和磷酸肌酸,但不影响长链酰基肉碱和辅酶的水平。这些酯类还能减少脂肪酸过氧化,如丙二醛所示,并且在防止超氧化物产生方面比肉碱更有效。在心肌细胞中,单独的丙酰-L-肉碱能刺激棕榈酸氧化,但在大鼠心脏匀浆中,L-肉碱和丙酰-L-肉碱均能刺激棕榈酸氧化,而乙酰-L-肉碱实际上具有抑制作用。丙酰-L-肉碱对缺血的保护作用的可能机制包括细胞转运速率增加、脂肪酸氧化的刺激以及自由基形成的减少。