Xiao C Y, Chen M, Hara A, Hashizume H, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Basic Res Cardiol. 1997 Oct;92(5):320-30. doi: 10.1007/BF00788944.
Long-chain acylcarnitines, such as palmitoyl-L-carnitine (PALCAR), are known to accumulate in the myocardium during ischemia. We examined whether exogenous PALCAR modifies the myocardial levels of high-energy phosphates (HEP) and free fatty acids (FFA) in the heart, and whether d-cis-diltiazem and l-cis-diltiazem, an optical isomer having less potent Ca2+ channel blocking action than d-cis-diltiazem, attenuate the PALCAR-induced myocardial changes. Rat hearts were perfused aerobically at a constant flow according to the Langendorff's technique, while being paced electrically. PALCAR (5 microM) decreased the tissue levels of adenosine triphosphate and creatine phosphate and increased the tissue level of adenosine monophosphate, and produced mechanical dysfunction. In addition, PALCAR (5 microM) increased markedly the tissue levels of FFA, especially those of arachidonic and palmitoleic acids, and the release of creatine kinase (CK) from the myocardium. These alterations in the myocardial levels of HEP and FFA induced by PALCAR were significantly attenuated by d-cis-diltiazem (15 microM) or l-cis-diltiazem (15 microM). Both drugs also attenuated the PALCAR-induced CK release. The present study demonstrates that PALCAR modifies the tissue levels of HEP and FFA in the heart and that both d-cis- and l-cis-diltiazem protect the myocardium against the PALCAR-induced changes through mechanisms other than Ca2+ channel blocking action.
长链酰基肉碱，如棕榈酰-L-肉碱（PALCAR），已知在缺血期间会在心肌中蓄积。我们研究了外源性PALCAR是否会改变心脏中高能磷酸盐（HEP）和游离脂肪酸（FFA）的心肌水平，以及d-顺式地尔硫䓬和l-顺式地尔硫䓬（一种钙通道阻滞作用比d-顺式地尔硫䓬弱的光学异构体）是否会减轻PALCAR诱导的心肌变化。按照Langendorff技术，在电起搏的同时，以恒定流量对大鼠心脏进行有氧灌注。PALCAR（5微摩尔）降低了三磷酸腺苷和磷酸肌酸的组织水平，增加了一磷酸腺苷的组织水平，并导致机械功能障碍。此外，PALCAR（5微摩尔）显著增加了FFA的组织水平，尤其是花生四烯酸和棕榈油酸的水平，以及心肌中肌酸激酶（CK）的释放。d-顺式地尔硫䓬（15微摩尔）或l-顺式地尔硫䓬（15微摩尔）可显著减轻PALCAR诱导的HEP和FFA心肌水平变化。两种药物还减轻了PALCAR诱导的CK释放。本研究表明，PALCAR会改变心脏中HEP和FFA的组织水平，并且d-顺式和l-顺式地尔硫䓬均通过钙通道阻滞作用以外的机制保护心肌免受PALCAR诱导的变化。
