Jones D L, Lo S
Department of Physiology and Medicine, University of Western Ontario, London, Canada.
Pharmacol Biochem Behav. 1990 Aug;36(4):979-83. doi: 10.1016/0091-3057(90)90109-u.
Cardiac glycosides are known to have a narrow therapeutic index, due in part to their effects on the brain. Injections of cardiac glycosides into the ventricles of the brain elicit activation of the autonomic nervous system, and may even elicit cardiac arrhythmias. However, the specific brain regions responsible for such action are unknown. The hypothalamus receives chemo- and baro-receptive innervation from the cardiovascular system. In turn, there are both direct and indirect effector pathways from the hypothalamus accessing the sympathetic preganglionic and parasympathetic ganglia regions. This suggests that the hypothalamus may be a prime candidate for the central toxic effects of cardiac glycosides. The purpose of this experiment was to map the rostral diencephalon to determine sites at which injections of a low dose of the cardiac glycoside, ouabain, resulted in altered cardiovascular responses in the anaesthetized rat. Microinjections of 20 ng of ouabain in 200 nl were made into sites throughout the rostral diencephalon of urethane (1.2 g/kg) anaesthetized rats while monitoring heart rate and blood pressure. Injections into the nucleus medianus, paraventricular, anterior and posterior hypothalamic nuclei produced increases in pressure of from 5 to 25 mmHg. These data suggest that part of the toxicity resulting from the cardiac glycoside administration may be due to the direct action of the glycosides on these hypothalamic structures. The paraventricular region has the greatest sensitivity and may be a primary target due to its direct connections with the preganglionic sympathetic regions in the spinal cord.
已知强心苷的治疗指数较窄，部分原因是其对大脑的影响。向脑室注射强心苷会引发自主神经系统的激活，甚至可能引发心律失常。然而，负责此类作用的具体脑区尚不清楚。下丘脑接受来自心血管系统的化学和压力感受器神经支配。反过来，下丘脑有直接和间接的效应通路通向交感神经节前和副交感神经节区域。这表明下丘脑可能是强心苷中枢毒性作用的主要候选部位。本实验的目的是绘制 Rostral 间脑图谱，以确定在麻醉大鼠中注射低剂量强心苷哇巴因会导致心血管反应改变的部位。在监测心率和血压的同时，将 200 nl 中含 20 ng 哇巴因的溶液微量注射到用乌拉坦（1.2 g/kg）麻醉的大鼠整个 Rostral 间脑的各个部位。向正中核、室旁核、下丘脑前核和后核注射会使血压升高 5 至 25 mmHg。这些数据表明，强心苷给药产生的部分毒性可能是由于苷类对这些下丘脑结构的直接作用。室旁区域具有最高的敏感性，由于其与脊髓中交感神经节前区域的直接连接，可能是主要靶点。
