McFalls E O, Paulson D J, Gilbert E F, Shug A L
Life Sci. 1986 Feb 10;38(6):497-505. doi: 10.1016/0024-3205(86)90028-7.
The effects of chronic adriamycin toxicity on myocardial carnitine content and contractile function were studied in rats, along with potential protective effects of L-carnitine administration. Cardiomyopathy was induced over a 6- to 7-week period by weekly intravenous injections of adriamycin, 2 mg/kg. In vivo myocardial tissue levels of carnitine were not significantly changed by adriamycin, but plasma levels were elevated. Cardiac output was depressed in isolated perfused hearts from adriamycin-treated rats perfused with 11 mM glucose. In a second experiment, 4-week-old male rats were divided into four groups: saline-treated control, L-carnitine-treated control, saline-treated adriamycin, and L-carnitine-treated adriamycin. L-Carnitine was given intraperitoneally each day at a dose of 500 mg/kg. Myocardial histology and ultrastructure were analyzed. Cardiac performance was determined in hearts perfused with 1.2 mM palmitate and 5.5 mM glucose. Hearts from saline-treated adriamycin rats showed histopathological changes and a significantly diminished cardiac output at various preloads when compared to saline-treated controls. Daily intraperitoneal L-carnitine reduced histopathological alterations and improved cardiac performance.
研究了慢性阿霉素毒性对大鼠心肌肉碱含量和收缩功能的影响,以及给予L-肉碱的潜在保护作用。通过每周静脉注射2mg/kg阿霉素,在6至7周的时间内诱导大鼠发生心肌病。阿霉素未使体内心肌组织的肉碱水平发生显著变化,但血浆水平升高。用11mM葡萄糖灌注阿霉素处理大鼠的离体灌注心脏时,心输出量降低。在第二个实验中,将4周龄雄性大鼠分为四组:生理盐水处理对照组、L-肉碱处理对照组、生理盐水处理阿霉素组和L-肉碱处理阿霉素组。每天以500mg/kg的剂量腹腔注射L-肉碱。分析心肌组织学和超微结构。在用1.2mM棕榈酸酯和5.5mM葡萄糖灌注的心脏中测定心脏功能。与生理盐水处理对照组相比,生理盐水处理阿霉素大鼠的心脏在不同前负荷下显示出组织病理学变化,心输出量显著降低。每天腹腔注射L-肉碱可减少组织病理学改变并改善心脏功能。