Sole M J, Benedict C R, Versteeg D H, de Kloet E R
J Mol Cell Cardiol. 1985 Nov;17(11):1055-63. doi: 10.1016/s0022-2828(85)80121-8.
The effect of therapeutic doses of digitalis in modifying neural activity has been the subject of considerable controversy. In earlier studies we reported an increase both in serotonergic activity in the posterior hypothalamus and pons-medulla and in cardiac sympathetic tone in the failing cardiomyopathic hamster. In this study we examine the effects of doses of digitoxin, known to be therapeutic for hamster heart failure, on monoamine neurotransmitter metabolism in the brain and heart during the cardiomyopathy. Both digitoxin and ASI-222, a polar amino-glycoside which does not cross the blood-brain barrier, given either acutely (6 mg/kg ip) or chronically (2 mg/kg/day ip for 10 days), normalized the failure-induced increase in serotonin turnover in the pons-medulla but had no effect on the changes in the posterior hypothalamus. Digitoxin therapy also reduced cardiac and adrenal sympathetic activity partially restoring cardiac catecholamine stores. In order to more clearly define the pathways involved we measured serotonin (microgram/g protein) in 18 brain nuclei after 10 days of digitoxin or vehicle treatment. Heart failure was associated with an increase in serotonin in five nuclei: the mammillary; bodies, ventromedial, periventricular and paraventricular nuclei of the hypothalamus, and the centralis superior nucleus of the raphe. Digitoxin therapy completely normalized the changes in the centralis superior and ventromedialis nuclei; neither congestive heart failure nor digitoxin affected serotonin levels in other nuclei. We conclude that there is an increase in activity in specific brain serotonergic nuclei in congestive heart failure. Digitalis reduces cardiac sympathetic tone and restores the changes in two of these nuclei: the ventromedial and the centralis superior.+2
治疗剂量的洋地黄对神经活动的影响一直是相当有争议的话题。在早期研究中，我们报告了在衰竭性心肌病仓鼠中，下丘脑后部和脑桥-延髓的血清素能活性以及心脏交感神经张力均有所增加。在本研究中，我们研究了已知对仓鼠心力衰竭有治疗作用的洋地黄毒苷剂量，对心肌病期间大脑和心脏中单胺类神经递质代谢的影响。无论是急性给予（腹腔注射6mg/kg）还是慢性给予（腹腔注射2mg/kg/天，持续10天），洋地黄毒苷和不能穿过血脑屏障的极性氨基糖苷类药物ASI-222，均使脑桥-延髓中因心力衰竭引起的血清素周转率增加恢复正常，但对下丘脑后部的变化没有影响。洋地黄毒苷治疗还降低了心脏和肾上腺的交感神经活动，部分恢复了心脏儿茶酚胺储备。为了更清楚地确定所涉及的途径，我们在给予洋地黄毒苷或赋形剂治疗10天后，测量了18个脑核中的血清素（微克/克蛋白质）。心力衰竭与五个核中的血清素增加有关：乳头体、下丘脑腹内侧核、室旁核和室周核，以及中缝上核。洋地黄毒苷治疗使中缝上核和腹内侧核的变化完全恢复正常；充血性心力衰竭和洋地黄毒苷均未影响其他核中的血清素水平。我们得出结论，充血性心力衰竭时特定脑血清素能核的活性增加。洋地黄降低心脏交感神经张力，并恢复其中两个核的变化：腹内侧核和中缝上核。
