Sleep spindle dynamics during NREM and REM sleep following distinct general anaesthesia in control rats and in a rat model of Parkinson’s disease cholinopathy

On the basis of our previous studies and the important role of the thalamo‐cortical network in states of unconsciousness, such as anaesthesia and sleep, and in sleep spindles generation, we investigated sleep spindles (SS) and high‐voltage sleep spindle (HVS) dynamics during non‐rapid eye movement (NREM) and rapid eye movement (REM) sleep following different types of general anaesthesia in both physiological controls and in a rat model of Parkinson's disease (PD) cholinopathy, to follow the impact of anaesthesia on post‐anaesthesia sleep at the thalamo‐cortical level through an altered sleep spindle dynamics. We recorded 6 hr of spontaneous sleep in all rats, both before and 48 hr after ketamine/diazepam or pentobarbital anaesthesia, and we used 1 hr of NREM or REM sleep from each to validate visually the automatically detected SS or HVS for their extraction and analysis. In the controls, SS occurred mainly during NREM, whereas HVS occurred only during REM sleep. Ketamine/diazepam anaesthesia promoted HVS, prolonged SS during NREM, induced HVS of increased frequency during REM, and increased SS/HVS densities during REM versus NREM sleep. Pentobarbital anaesthesia decreased the frequency of SS during NREM and the HVS density during REM sleep. Although the pedunculopontine tegmental nucleus lesion prolonged SS only during NREM sleep, in these rats, ketamine/diazepam anaesthesia suppressed HVS during both sleep states, whereas pentobarbital anaesthesia promoted HVS during REM sleep. The different impacts of two anaesthetic regimens on the thalamo‐cortical regulatory network are expressed through their distinct sleep spindle generation and dynamics that are dependent on the NREM and REM state regulatory neuronal substrate.     

Valproic acid induction of coma in rats: Synergism with NH 4 + and pentobarbital

Dose-response curves for the incidence of coma after intraperitoneal injections of various doses of valproic acid (VP) and octnoic acid (OA) showed that, mole for mole, valproic acid was less toxic than octanoic acid. However, a simultaneous subcoma dose of pentobarbital (PB) enhanced the toxicity of VP more than that of OA. The dose-response curve for NH₄C1 was affected by simultaneous subcoma doses of VP and OA but not by PB. VP enhanced the toxicity of the NH ₄ ⁺ by 52%; OA enhanced the toxicity by 12%. PB added significantly to the toxicity of VP and NH ₄ ⁺ when the three were given simultaneously. Doses of 0.7 mmol NH ₄ ⁺ and 0.5 mmol VP given separately had little or no encephalopathic effect, with blood ammonias of 250–1250g/dl. When given simultaneously they induced a deep coma and raised the blood ammonia threefold, to about 3600g/dl. Similar doses of OA and NH ₄ ⁺ , induced a similar deep coma, but blood levels of ammonia were not as high. Simultaneous injections of 250 mg glucose did not alter the results. Thus VP toxicity is enhanced substantially by its synergistic interactions with PB and the NH ₄ ⁺ .     

龙牙葱木皂苷对实验性心力衰竭大鼠心功能的影响

目的：观察龙牙葱木皂苷(Aralosides,As)对实验性心力衰竭大鼠血流动力学的影响。 方法：Wistar大鼠24只,静脉注射1.5%戊巴比妥钠溶液成功建立心力衰竭模型平稳5 min后,阴性对照组、As实验组及阳性药物对照组各8只大鼠,分别静脉注射生理盐水（0.9 mg•kg^-1）、龙牙葱木皂苷（As,10 mg•kg^-1）和去乙酰毛花甙（0.04 mg•kg^-1）,各组均以心力衰竭模型后5 min时的各项心功能指标为对照,采用四导生理记录仪同步记录正常时、心衰后5 min以及静脉给药后30 min内各组大鼠的左室收缩压（LVSP）、左室最大上升和下降速率（±dp/dt^max）、左室舒末压（LVEDP）、收缩压（SAP）、舒张压（DAP）和心率（HR）等心功能指标,计算机监视记录结果及分析,用彩色绘图仪绘制曲线。 结果：心力衰竭模型大鼠静脉注射As后,LVSP由（10.8±1.0） kPa增加到（14.5±1.8） kPa （P<0.001）,+dp/dt^max由（163±24）kPa•s^-1增加到（295±66） kPa•s^-1 （P<0.001）,-dp/dt^max由（-140±31） kPa•s^-1下降到（-218±60）kPa•s^-1（P<0.01）,LVEDP由（1.46±0.24）kPa下降到（1.28±0.17）kPa（P<0.05）;静脉注射去乙酰毛花甙后,LVSP由（10.5±1.2）kPa增加到（12.9±1.6）kPa（P<0.01）,+dp/dt^max由（144±26）kPa•s^-1增加到（222±53）kPa•s^-1（P<0.001）,-dp/dt^max由（-132±23） kPa•s^-1下降到（-190±32）kPa•s^-1 （P<0.001）,LVEDP由（1.31±0.19）kPa可下降到（1.14±0.18）kPa（P<0.05）;而心力衰竭大鼠静脉注射生理盐水后,其心功能的各项指标较注射生理盐水前均无明显改变（P>0.05）。结论：As具有与去乙酰毛花甙一致的抗心力衰竭。     

萨木与扎冲合用对猫实验性心力衰竭和心源性休克的影响

目的 观察萨木和扎冲注射液合用对心力衰竭和心源性休克的作用。方法 给麻醉猫注射戊巴比妥钠制造实验性心力衰竭和心源性休克的模型，然后给药观察。结果 萨木格扎冲注射液合用可使左心室收缩压、左室压力最大变化率、心输出量及平均动脉压明显增加，左心室舒张末期压明显降低。结论：萨木和扎冲液射液合用可增强麻醉猫衰竭心脏的心肌收缩力和心脏泵血功能，具有明显改善心功能的作用。     

Control of the neuronal rhythmic bursts in the septal pacemaker of theta-rhythm: Effects of anaesthetic and anticholinergic drugs

The drugs, described as blocking the high-frequency (pentobarbital) or low-frequency (scopolamine, atropine) theta rhythm of the hippocampal electroencephalogram, were tested upon the rhythmically bursting septal cells. Three groups of chronic, unanaesthetized rabbits were used for the experiments: with intact septum; with septohippocampal disconnection; with complete basal undercutting of the septum, depriving it of ascending brainstem influences (MFB lesion). While the frequency and other parameters of theta bursts did not differ in the first two groups (5.2-5.5 Hz), in MFB-lesioned septum their frequency was significantly lower (3.5 Hz). Intravenous injection of pentobarbital suppressed theta bursts in some cells with unstable, periodic rhythmic activity and lowered the frequency of the bursts in continuously bursting cells. The parameters of bursts in intact and hippocampectomized septum under pentobarbital did not differ from those of undercut septum in undrugged state. Acetylcholine-blocking drugs suppressed theta modulation in some intermittently bursting cells, but only slightly decreased regularity of the bursts in some cells with continuous theta bursting even in sublethal doses; physostigmine has the opposite effect. Neither scopolamine and atropine, nor physostigmine influenced frequency of theta bursts in any way. Sensory or reticular stimulation could temporarily restore both the theta rhythm of hippocampal EEG and the rhythmic bursting of some septal cells under pentobarbital or anticholinergic drugs. On the basis of the experiments a unitary concept of theta rhythm origin is proposed. Pentobarbital influences ascending excitatory input to the septum, which results in a decrease of the burst frequency in the limited group of septal cells, regarded as endogenous bursting pacemakers, and in restriction of the population of high-threshold secondary rhythmic cells, synaptically involved in the rhythmic process. Anticholinergic drugs do not influence the pacemaker cells, but block intraseptal and septohippocampal cholinergic transmission. Both cholinergic and non-cholinergic neurons projecting to the hippocampus exist among septal cells synaptically involved in the rhythmic activity.     

戊巴比妥对大鼠肺动脉压和肺血管阻力的影响

本文观察戊巴比妥对整体大鼠及离体大鼠肺灌流的作用。在整体大鼠,戊巴比妥15mg/kg,30mg/kg降低系统动脉压,同时也降低肺动脉压。二者呈同步性下降。在恒速灌流的离体大鼠肺,肺动脉压直接反映肺血管阻力。戊巴比妥使低氧引起的肺动脉压升高恢复到基线水平,并能抑制再次低氧刺激引起的肺动脉压升高。提示戊巴比妥降低肺动脉压的作用与其减少肺血管阻力有关。     

Single-Subject design for locomotor activity

Rats were given daily 1-hr sessions in photocell cages until baseline locomotion stabilized. d-Amphetamine 0.5–2.0 mg/kg p.o. significantly increased locomotion. Chlorpromazine 2.5–20 mg/kg p.o. and pentobarbital 5.0–20 mg/kg p.o. significantly decreased locomotion. N = 4 per drug. Results demonstrate the appropriateness of using chronic single subjects to assess the effects of drugs on locomotion. An attempt to generate cumulative dose-effect curves in rats run once a week was less successful because of intrasubject variability. The method could also be used for multiple drug studies in lesioned or cannulated preparations.     

Responses to barbiturates of isolated dog cerebral and mesenteric arteries contracted with KCl and prostaglandin F2a

In helical strips of dog cerebral and mesenteric arteries previously contracted with KCl or prostaglandin F2 alpha (PGF2 alpha), the addition of pentobarbital (10(-5) to 10(-3) mol.l-1) caused dose-related relaxation, whereas thiamylal and thiopental in a low concentration (10(-5) to 10(-4) mol.l-1) caused further contraction and in a high concentration (10(-3) mol.l-1) profound relaxation. Thiobarbiturate-induced contractions were greater in mesenteric than in cerebral arteries previously contracted with PGF2 alpha. In cerebral and mesenteric arteries exposed to Ca(++)-free media for 60 min and treated with KCl or PGF2 alpha, reintroduction of Ca++ produced a transient contraction, a transient relaxation and a persistent contraction. The Ca(++)-induced persistent contraction was attenuated by pretreatment with pentobarbital (10(-4) to 10(-3) mol.l-1) and thiamylal (10(-3) mol.l-1); the attenuation was greater in arteries treated with KCl than with PGF2 alpha. The Ca(++)-induced contractions of mesenteric artery treated with PGF2 alpha were potentiated by 10(-4) mol.l-1 thiamylal. It is concluded that pentobarbital possesses only a vasodilator effect, whereas thiamylal and thiopental have both constrictor and dilator effects on vascular smooth muscle. The vasodilator effect of barbiturates is associated in part with inhibition of transmembrane influx of Ca++; the inhibition is more predominant on the influx evoked by KCl-induced depolarization than by a stimulation of PGF2 alpha receptors. Thiamylal in low concentrations appears to enhance Ca++ influx through a receptor-operated Ca++ channel for PGF2 alpha.     

Synthesis and central nervous system actions of thyrotropin-releasing hormone analogs containing a 1-substituted 2-oxoimadazolidine moiety*

A series of thyrotropin-releasing hormone (TRH) analogs in which the pyroglutamic acid residue was replaced by (S)-2-oxoimidazolidine-4-carboxylic acid (Oic-OH) and the related derivatives was prepared, and the central nervous system (CNS) actions were examined. Of these, 1-benzyl-Oic-His-Pro-NH₂ (2c) showed the most potent activities, which were 1.5-8 times greater than those of TRH. Moreover, the thyrotropin (TSH)-releasing activity of 2c was about 1/16 times weaker than that of TRH.