Thirty hypertensive patients scheduled for cholecystectomy or hernia repair under general anaesthesia with thiopentone-fentanyl-nitrous oxide-pancuronium were divided into two groups of 15. One group received metoprolol tablets 200 mg in a slow release form, once daily for at least 2 weeks including the morning of surgery. In addition, metoprolol 15 mg was injected i.v. shortly before the induction of anaesthesia. The other group received placebo tablets and saline. Two patients in the treatment group and one patient in the placebo group were subsequently excluded, because of complications during treatment. Metoprolol significantly reduced arterial pressure both during undisturbed anaesthesia, during intubation and after extubation. A similar tendency was observed also during surgery, although it was not quite significant (P = 0.055). However, metoprolol had no effect on variations in systemic vascular resistance. Mean pulmonary arterial pressures during anaesthesia and surgery were significantly greater in the control, than in the metoprolol, group. Central venous pressure (CVP) and pulmonary arterial occlusion pressure (PAOP) increased significantly in both groups in response to the surgical stimulus. There was no significant difference between the groups in PAOP and CVP. One patient in the metoprolol group had marked bradycardia (minimum heart rate 26 beat min-1) after neostigmine and atropine; otherwise metoprolol pretreatment was tolerated well.

Forty-four children, ASA physical status I or II, aged 1.5-14 years and admitted for strabismus surgery, were studied. The study compared the postoperative condition after two different anesthesia methods. All children were premedicated with midazolam rectally, received glycopyrrolate i.v. and were then randomised to one of two anesthetic methods: 1) induction with thiopental, maintenance with halothane or 2) induction with propofol supplemented with fentanyl, maintenance with propofol infusion. In both groups, tracheal intubation was performed after vecuronium i.v. and the children were ventilated manually. Peroperatively, patients receiving propofol/fentanyl had more episodes of bradycardia (P less than 0.001). Times to spontaneous breathing and extubation were shorter in the propofol/fentanyl group (P less than 0.05) and there was also a lesser degree of sedation during the first 2 h postoperatively (P less than 0.01). Fewer children in the propofol/fentanyl group vomited postoperatively (P less than 0.05). The apprehension score was higher in the propofol/fentanyl group compared to the thiopental/halothane group (P less than 0.05). We conclude that children undergoing strabismus surgery anesthetized with propofol/fentanyl had more episodes of peroperative bradycardia, a lower incidence of postoperative vomiting and a shorter recovery time, and were more apprehensive during the initial postoperative period than children anesthetized with thiopental/halothane.

The role of brain stem serotonin (5-hydroxytryptamine, 5-HT) in autoresuscitation in neonatal life is unclear. We hypothesized that a specific loss of 5-HT would compromise gasping and autoresuscitation mainly in the second postnatal week and that acute restoration of 5-HT would reverse the defects. We exposed postnatal day (P)4-5, P8-9, and P11-12 tryptophan-hydroxylase-2 knockout (TPH2(-/-)) and wild-type littermates (WT) to 10 episodes of anoxia (97% N2, 3% CO2), measuring survival, gasp latency, gasp frequency (fB), and the time required to restore eupnea and heart rate. We also tested P8-9 TPH2(-/-) mice after restoring 5-HT with a single injection of 5-hydroxytryptophan (5-HTP) 1-2 h before testing or with multiple injections beginning 24 h before testing. At P4-5 and P8-9, but not at P11-12, gasp latency and the recovery of eupnea were delayed ~2- to 3-fold in TPH2(-/-) pups compared with WT (P < 0.001). At all ages, TPH2(-/-) pups displayed reduced gasp fB (~20-30%; P < 0.001) and delayed heart rate recovery (~60%; P = 0.002) compared with WT littermates. TPH2(-/-) survival was reduced compared with WT (P < 0.001), especially at P8-9 and P11-12 (P = 0.004). Whereas 1-2 h of 5-HTP treatment improved the gasp latency and fB of P8-9 TPH2(-/-) pups, improved cardiorespiratory recovery and survival required 24 h of treatment. Our data suggest that 5-HT operates over a long time span (24 h) to improve survival during episodic severe hypoxia. Early in development (P4-9), 5-HT is critical for both respiratory and cardiovascular components of autoresuscitation; later (P11-12), it is critical mainly for cardiovascular components. Nevertheless, the effect of 5-HT deficiency on survival is most striking from P8 to P12.

Basal ganglia dysfunction is implicated in movement disorders including Parkinson Disease, dystonia, and choreiform disorders. Contradicting standard “rate models” of basal ganglia-thalamic interactions, internal pallidotomy improves both hypo- and hyper-kinetic movement disorders. This “paradox of stereotaxic surgery” was recognized shortly after rate models were developed, and is underscored by the outcomes of deep brain stimulation (DBS) for movement disorders. Despite strong evidence that DBS activates local axons, the clinical effects of lesions and DBS are nearly identical. These observations argue against standard models in which GABAergic basal ganglia output gates thalamic activity, and raise the question of how lesions and stimulation can have similar effects. These paradoxes may be resolved by considering thalamocortical loops as primary drivers of motor output. Rather than suppressing or releasing cortex via motor thalamus, the basal ganglia may modulate the timing of thalamic perturbations to cortical activity. Motor cortex exhibits rotational dynamics during movement, allowing the same thalamocortical perturbation to affect motor output differently depending on its timing with respect to the rotational cycle. We review classic and recent studies of basal ganglia, thalamic, and cortical physiology to propose a revised model of basal ganglia-thalamocortical function with implications for basic physiology and neuromodulation.

Sudden infant death syndrome (SIDS) is associated with serotonin (5-HT) neuron abnormalities. There is evidence of autonomic dysfunction during sleep in infants eventually succumbing to SIDS, as well as cardiovascular collapse before death. Neonatal rodents deficient in central 5-HT display hypotension and bradycardia. We hypothesized that central 5-HT reduces cardiac vagal tone and increases sympathetic vascular tone and, given the firing pattern of 5-HT neurons, that these effects are greater in quiet sleep (QS) than in active sleep (AS). We tested these hypotheses using 2-wk-old male and female rat pups lacking tryptophan hydroxylase-2 ( TPH2) and wild-type (WT) littermates. Arterial blood pressure (ABP) and heart rate (HR) were measured over 3 h during periods of QS and AS. We also gave atropine or atenolol (each 1 mg/kg iv), or phentolamine (5, 50, and 500 μg/kg iv) to separate groups to assess the effects 5-HT deficiency on autonomic tone to the heart or sympathetic vascular tone, respectively. Compared with WT, male and female TPH2 pups had reduced ABP in QS but not in AS. Atropine induced a greater HR increase in female TPH2 than in female WT pups, an effect absent in male TPH2 pups. Both genotypes experienced the same atenolol-induced drop in HR. In males only, phentolamine induced a smaller decrease in the ABP of TPH2 pups compared with WT. These data suggest that central 5-HT maintains ABP in QS, and HR in both states. In males, central 5-HT facilitates sympathetic vascular tone, and in females it reduces cardiac vagal drive.