Nishimura H, Yoshikawa T, Kobayashi N, Anzai T, Nagami K, Handa S, Ogawa S
Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
Heart Vessels. 1997;12(2):84-91. doi: 10.1007/BF02820871.
Studies suggest that corticosteroids may restore the responsiveness to catecholamines in hypotensive patients. Since the significance of this promising intervention in congestive heart failure remains to be explored, we determined the effects of methylprednisolone, a potent activator of beta-adrenergic receptor signaling, on hemodynamics and beta-adrenergic receptor regulation in an animal model of heart failure. Acute left ventricular overloading was produced by aortic regurgitation (AR) in 22 Japanese white rabbits. Eleven animals received an intravenous administration of methylprednisolone (AR + PSL), while 11 received saline (AR + C) for 1 week. A sham operation was performed on 10 other rabbits (S). There was no difference between the AR + C and AR + PSL groups in the decrease in aortic diastolic pressure immediately after the production of AR. The aortic diastolic pressure and regurgitant fractions were also similar in the two groups. The left ventricular end-diastolic and end-systolic dimensions were both larger, and the left ventricular end-diastolic pressure was higher in AR + C or AR + PSL than in S rabbits. Between the AR + C and AR + PSL, there were no differences in any of these variables. Cardiac output was lower in AR + C, but not in AR + PSL, than in S. Cardiac output in AR + PSL was significantly higher than in AR + C. The myocardial concentration of norepinephrine and the number of beta-adrenergic receptors were both lower in the AR + C and AR + PSL than in the S groups. The number of receptors in AR + PSL was higher than in AR + C. Maximal isoproterenol-stimulated adenylyl cyclase activity was similar in the AR + C and AR + PSL groups. Results suggest methylprednisolone yielded some benefits, including an increase in cardiac output and in total beta-adrenergic receptor number, in this animal model of heart failure.
研究表明，皮质类固醇可能会恢复低血压患者对儿茶酚胺的反应性。由于这种有前景的干预措施在充血性心力衰竭中的意义仍有待探索，我们在心力衰竭动物模型中确定了β-肾上腺素能受体信号的强效激活剂甲泼尼龙对血流动力学和β-肾上腺素能受体调节的影响。通过主动脉反流（AR）在22只日本白兔中造成急性左心室超负荷。11只动物接受甲泼尼龙静脉注射（AR + PSL），而11只接受生理盐水注射（AR + C），持续1周。对另外10只兔子进行假手术（S）。在产生AR后立即，AR + C组和AR + PSL组在主动脉舒张压降低方面没有差异。两组的主动脉舒张压和反流分数也相似。AR + C组或AR + PSL组的左心室舒张末期和收缩末期尺寸均更大，且左心室舒张末期压力高于假手术组兔子。在AR + C组和AR + PSL组之间，这些变量中的任何一个均无差异。AR + C组的心输出量低于假手术组，而AR + PSL组的心输出量不低于假手术组。AR + PSL组的心输出量显著高于AR + C组。AR + C组和AR + PSL组中去甲肾上腺素的心肌浓度和β-肾上腺素能受体数量均低于假手术组。AR + PSL组中的受体数量高于AR + C组。AR + C组和AR + PSL组中最大异丙肾上腺素刺激的腺苷酸环化酶活性相似。结果表明，在这个心力衰竭动物模型中，甲泼尼龙产生了一些益处，包括心输出量增加和总β-肾上腺素能受体数量增加。
