C. Kidd

Neuronal nitric oxide facilitates vagal chronotropic and dromotropic actions on the heart.

Previous studies, using non-specific nitric oxide synthase (NOS) inhibitors, have shown that nitric oxide (NO) has a significant facilitatory effect on the actions of the vagus nerve on several aspects of cardiac function. The present study aims to identify a potential neuronal site for the action of NO by using the n-NOS inhibitor, 1-(2-trifluoromethylphenyl) imidazole (TRIM) in the ferret and other mammals. The effects of TRIM on vagally evoked alterations in heart rate and atrio-ventricular (a-v) conduction in the anaesthetised ferret, rabbit and guinea pig are described. In ferrets with both vagi sectioned and repeated infusions of propranolol, the vagally evoked, frequency-dependent bradycardia was significantly attenuated by infusion of TRIM (10-30 mg kg(-1)). This effect was reversed by subsequent infusion of L-arginine (20-6 mg kg(-1)). TRIM also attenuated to a similar extent the vagally evoked bradycardia in similarly prepared guinea pigs, but NOS inhibition and the use of the NO donor, molsidimine, failed to alter the heart rate effects of vagal stimulation in the rabbit. In studies on a-v conduction (dromotropy) in the ferret, electrical stimulation of the left cervical vagus increased the a-v conduction time in a frequency-dependent manner. Administration of TRIM (30 mg kg(-1)) significantly attenuated this response. Again, L-arginine (60 mg kg(-1)) reversed it. Since an alteration in heart rate may have a concomitant action on a-v conduction time, the effects of vagal stimulation on a-v conduction were also carried out in ferrets with the heart paced at a constant rate electrically. There was no significant difference between the effects of vagal stimulation obtained from hearts which were paced and those which were unpaced. This implies that vagal stimulation had a direct effect on a-v delay and the changes were not secondary to alterations in cardiac rate. Based on other evidence that TRIM is a powerful reversible n-NOS inhibitor in vivo, our studies support strongly the hypothesis that NO liberated from neuronal sources has an important facilitatory action on the vagal control of the heart. In relation to vagal heart rate control, it has now been shown that, in line with other studies in the dog and the rat, NO exerts a powerful facilitatory action in the ferret and the guinea pig but not in the rabbit. It is to be expected that these effects of NO will also be demonstrable on other vagal cardiac actions.

Modulation of vagal actions on heart rate produced by inhibition of nitric oxide synthase in the anaesthetized ferret

We have examined a possible role for nitric oxide in the efferent vagal control of heart rate of the anaesthetized ferret, using stimulation of the motor fibres of the right vagus at supramaximal intensities and increasing frequencies. Propranolol was used to block beta‐adrenergic actions on the heart. L‐NAME (50–100 mg i.v.) significantly reduced the bradycardia induced by vagal stimulation at all frequencies tested (1–15 Hz); subsequent infusion of L‐arginine (100–200 mg i.v.) restored the vagally induced heart rate responses to control levels. These results strongly suggest a role for nitric oxide in modulating the vagally mediated control of heart rate.

Laser Doppler Study of Porcine Cauda Equina Blood Flow: The Effect of Electrical Stimulation of the Rootlets During Single and Double Site, Low Pressure Compression of the Cauda Equina

Study Design This study involved a model of spinal claudication to assess the effect of single and double site compressions on blood flow in porcine cauda equina. Real-time monitoring of blood flow was achieved by using laser Doppler probes. Objectives To ascertain the difference between single and double site compressions on blood flow and nerve conduction in the cauda equina. Also, to provide possible explanations for the mechanisms underlying the pathophysiology of neurogenic claudication. Summary of Background Data The model used was based on that of K. Olmarker. Double as compared with single site compression of cauda equina showed impaired nerve impulse propagation and decreased blood flow. Method Pigs weighing 22–27 kg were anesthetized and the cauda equina was exposed by dorsal laminectomy of the sacral and first three coccygeal vertebrae. Polyethylene balloons were placed over the rootlets at the first and third coccygeal segments, and stimulating electrodes were positioned on the rootlets proximally to evoke motor activity. Electromyographic activity was monitored from tail musculature. Laser Doppler probes monitored blood flow in the cauda equina both between and distal to the two compression sites. Results Single site, low level compression did not affect blood flow whereas double site compression decreased it profoundly. Proximal stimulation caused a marked increase in blood flow, which was not sustained during prolonged compression. Electromyographic activity diminished concomitantly during this compression. Conclusions Low pressure, double site compression significantly reduces cauda equina blood flow and prevents the sustained increase in blood flow required to maintain normal neurologic rootlet function. Local blood flow failure may therefore be responsible for claudication symptoms.

Neurones in the dorsal motor vagal nucleus of the cat with non-myelinated axons projecting to the heart and lungs.

Extracellular recordings were made from ninety‐four single motoneurones in the dorsal motor vagal nucleus of chloralose‐anaesthetized or decerebrate cats. Fifty‐five neurones had axons in cardiac vagal branches and thirty‐nine had axons in pulmonary vagal branches; the conduction velocities of the axons were in the C fibre range, i.e. the axons were non‐myelinated. The neurons exhibited little or no spontaneous activity. Excitatory and inhibitory synaptic inputs were demonstrated by electrical stimulation of the vagus nerve or its branches. Twenty‐four neurones were tested by carotid sinus distension but only one was excited. Iontophoretic excitation of neurones projecting to cardiac vagal branches had no effect on heart rate. The properties of these neurones and their possible functions are discussed and contrasted with those of cardiac and pulmonary vagal motoneurones in the nucleus ambiguus.

THE ROLE OF NITRIC OXIDE IN THE CONTROL BY THE VAGAL NERVES OF THE HEART OF THE FERRET

This study focuses on the potential role for nitric oxide on the actions of the parasympathetic innervation to the heart. Earlier, we showed that the nitric oxide synthase (NOS) inhibitor N omega‐nitro‐L‐arginine methyl ester (L‐NAME) reduced the bradycardia induced by stimulation of vagal efferent motor fibres and that these effects are reversible through administration of the NOS substrate L‐arginine. In the present study, we show that D‐arginine does not reverse the effects of the inhibitors and confirm that they are reversed by L‐arginine. Another NOS inhibitor, NG‐nitro‐L‐arginine (L‐NOARG), produced similar effects which were not reversed by L‐arginine. In an examination of the effect of increasing NO availability with the NO donor sodium nitroprusside the vagally induced bradycardia was enhanced at all frequencies tested. In a separate series, the effects of NOS inhibitors and NO donors on the dromotropic actions of the vagus were examined. The NOS inhibitor L‐NAME, reduced the increase in atrio‐ventricular conduction delay normally induced by efferent vagal stimulation at all frequencies tested both in the ‘paced’ and ‘unpaced’ heart. Further, sodium nitroprusside enhanced this delay. Overall the study indicates that NO has an important facilitatory role on both the chronotropic and dromotropic actions of the vagus nerve on the heart and that NO may be a rate‐limiting factor in the cardiac responses to vagal stimulation.

Nitric oxide facilitates vagal control of heart rate via actions in the cardiac parasympathetic ganglia of the anaesthetised dog

The effects of neuronal inhibition of nitric oxide (NO) production on the bradycardia resulting from stimulation of preganglionic and postganglionic parasympathetic fibres were investigated in an anaesthetised dog preparation following transection of the cervical vagi and in the presence of a β‐adrenoreceptor antagonist. Injection of 1‐(2‐trifluoromethylphenyl) imidazole (TRIM), an inhibitor of neuronally released NO, into the sinus node artery reduced the bradycardia evoked by right cervical vagal stimulation. In contrast, when the response to preganglionic stimulation had been abolished by hexamethonium (10 mg kg−1), the bradycardia following stimulation of postganglionic parasympathetic fibres on the atrial epicardium was unaffected by TRIM. First, these results confirm the facilitatory actions of neuronally released NO on vagal heart responses in the dog. Second, they indicate that this modulatory and facilitatory role of NO is likely to be exerted at vagal preganglionic‐postganglionic synaptic mechanisms in the cardiac parasympathetic ganglia and not at the postganglionic‐sinoatrial node synapse.

Inhibition of Neuronal Nitric Oxide Reduces Heart Rate Variability in the Anaesthetised Dog

In the vagally intact anaesthetised dog, we have investigated the role of nitric oxide (NO) on a normal sinus arrhythmia using an inhibitor of neuronally released NO, 1‐(2‐trifluoromethylphenyl) imidazole (TRIM). The mean and S.D. of the R‐R interval was used to describe mean heart rate and heart rate variability, respectively. TRIM (0.8 mg I.C.) injected into the sinus node artery increased the mean heart rate slightly but reduced heart rate variability 3‐fold from a control of 790 ± 124 ms (mean ± S.D.; n = 5) to 666 ± 36 ms (P < 0.01 Students paired t test, n = 5). These results suggest that neuronally released NO may have a vagal facilitatory role in the maintenance of sinus arrhythmia in the normal heart.

An Anthropological Study of the Elderly Patient in an Adult Psychiatric Clinic

RECENT years have been marked by advances in clinical and social research on the problems and policies involved in the care of the elderly, both in the geriatric wards of mental hospitals and in other treatment systems catering specifically for this age group. Outside this frame of reference, relatively little is known about the situations affecting old people who have treatment in psychiatric units which provide for a patient population that is heterogeneous in age and in diagnostic composition.