Sethi Rajat, Wang Xi, Ferrari Roberto, Dhalla Naranjan S
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre and Department of Physiology, University of Manitoba, Winnipeg, Canada.
Coron Artery Dis. 2004 Feb;15(1):65-71. doi: 10.1097/00019501-200402000-00010.
Earlier studies have revealed beneficial effects of metabolic therapy in animals with congestive heart failure (CHF) due to myocardial infarction. Because heart failure is also associated with attenuated response to catecholamines, we examined the effects of propionyl L-carnitine (PLC) (a carnitine derivative) therapy on the beta-adrenoceptor (beta-AR) signal transduction in the failing heart.
Heart failure in rats was induced by occluding the coronary artery and 3 weeks later the animals were treated with or without 100 mg/kg (intraperitoneally, daily) PLC for 5 weeks. The animals were assessed for their left ventricular function and inotropic responses to isoproterenol. Crude membranes were isolated from the remote, nonischemic (viable) left ventricle and examined for changes in beta-AR and adenylyl cyclase (AC) activity.
Animals with heart failure exhibited depressions in ventricular function, positive inotropic response to isoproterenol, beta-AR receptor density and basal AC activity; these changes were also attenuated by PLC treatment. The stimulation of AC activities with isoproterenol, 5'-guanyl imidodiphosphate, forskolin and sodium fluoride was decreased in the failing hearts and these changes were also prevented by PLC treatment.
The results indicate that metabolic therapy with PLC not only attenuates the defects in heart function but also prevents changes in the beta-AR signal transduction in CHF due to myocardial infarction.
早期研究已揭示代谢疗法对因心肌梗死所致充血性心力衰竭（CHF）动物有益。由于心力衰竭还与对儿茶酚胺反应减弱有关，我们研究了丙酰-L-肉碱（PLC）（一种肉碱衍生物）疗法对衰竭心脏中β-肾上腺素能受体（β-AR）信号转导的影响。
通过结扎冠状动脉诱导大鼠心力衰竭，3周后，动物接受或不接受100mg/kg（腹腔注射，每日）PLC治疗5周。评估动物的左心室功能及对异丙肾上腺素的变力反应。从远离缺血区的非缺血（存活）左心室分离粗制细胞膜，检测β-AR和腺苷酸环化酶（AC）活性的变化。
心力衰竭动物表现出心室功能降低、对异丙肾上腺素的正性变力反应、β-AR受体密度及基础AC活性降低；这些变化也因PLC治疗而减轻。在衰竭心脏中，异丙肾上腺素、5'-鸟苷亚胺二磷酸、福斯高林和氟化钠对AC活性的刺激作用降低，且这些变化也因PLC治疗而得到预防。
结果表明，PLC代谢疗法不仅减轻心脏功能缺陷，还可预防心肌梗死所致CHF中β-AR信号转导的变化。
