Long-term effects of spinal cord stimulation on myocardial ischemia and heart rate variability: results of a 48-hour ambulatory electrocardiographic monitoring.

BACKGROUND: Spinal cord stimulation (SCS) has analgesic properties and may be used to treat pain in patients with therapeutically refractory angina who are unsuitable for myocardial revascularization. Some studies have also demonstrated an anti-ischemic effect. The aim of this study was to evaluate the long-term persistence of the effects of SCS on myocardial ischemia and on heart rate variability. METHODS: Fifteen patients (9 males, 6 females, mean age 76 +/- 8 years, range 58-90 years) with severe refractory angina pectoris (Canadian class III-IV), on optimal pharmacological therapy, unsuitable for myocardial revascularization and treated with SCS for a mean follow-up of 39 +/- 27 months (range 9-92 months) were studied. Eleven patients had had a previous myocardial infarction and 5 a coronary artery bypass graft. The mean ejection fraction was 54 +/- 7% (range 36-65%). All patients underwent 48-hour ambulatory ECG monitoring and were randomly assigned to 24 hours without SCS (off period) and 24 hours with SCS (on period). The primary endpoints were: number of ischemic episodes, total duration of ischemic episodes (min), and total ischemic burden (mV*min). RESULTS: The heart rate was not statistically different during the off and on SCS periods (median 64 and 67 b/min respectively). The number of ischemic episodes decreased from a median of 6 (range 0-29) during the off period to 3 (range 0-24) during the on period (p < 0.05). The total duration of ischemic episodes decreased from a median of 29 min (range 0- 186 min) during the off period to 16 min (range 0-123 min) during the on period (p < 0.05). The total ischemic burden decreased from a median of 2.5 mV*min (range 0-19.5 mV*min) during the off period to 0.8 mV*min (range 0-13 mV*min) during the on period (p = NS). The heart rate variability parameters were similar during the on and off periods. CONCLUSIONS: SCS exerts long-term anti-ischemic effects.

Coding and adaptation during mechanical stimulation in the leech nervous system.

The experiments described here were designed to characterise sensory coding and adaptation during mechanical stimulation in the leech (Hirudo medicinalis). A chain of three ganglia and a segment of the body wall connected to the central ganglion were used. Eight extracellular suction pipettes and one or two intracellular electrodes were used to record action potentials from all mechanosensory neurones of the three ganglia. When the skin of the body wall was briefly touched with a filament exerting a force of about 2 mN, touch (T) cells in the central ganglion, but also those in adjacent ganglia (i.e. anterior and posterior), fired one or two action potentials. However, the threshold for action potential initiation was lower for T cells in the central ganglion than for those in adjacent ganglia. The timing of the first evoked action potential in a T cell was very reproducible with a jitter often lower than 100 us. Action potentials in T cells were not significantly correlated. When the force exerted by the filament was increased above 20 mN, pressure (P) cells in the central and neighbouring ganglia fired action potentials. Action potentials in P cells usually followed those evoked in T cells with a delay of about 20 ms and had a larger jitter of 0.5-10 ms. With stronger stimulations exceeding 50 mN, noxious (N) cells also fired action potentials. With such stimulations the majority of mechanosensory neurones in the three ganglia fired action potentials. The spatial properties of the whole receptive field of the mechanosensory neurones were explored by touching different parts of the skin. When the mechanical stimulation was applied for a longer time, i.e. 1 s, only P cells in the central ganglion continued to fire action potentials. P cells in neighbouring ganglia fully adapted after firing two or three action potentials.P cells in adjacent ganglia, having fully adapted to a steady mechanical stimulation of one part of the skin, fired action potentials following stimulation of a different region of the skin. These results indicate that a brief and localised stimulation of the skin can activate more than a dozen different mechanosensory neurones in the three ganglia and after 100 ms of steady stimulation many of these mechanosensory neurones stop firing action potentials and fully adapt. Adaptation occurs primarily at the nerve endings and mechanosensory neurones can quickly respond to mechanical stimulation at a different location on the skin.

Statistical independence and neural computation in the leech ganglion.

In this report, the input/output relations in an isolated ganglion of the leech Hirudo medicinalis were studied by simultaneously using six or eight suction pipettes and two intracellular electrodes. Sensory input was mimicked by eliciting action potentials in mechanosensory neurons with intracellular electrodes. The integrated neural output was measured by recording extracellular voltage signals with pipettes sucking the roots and the connectives. A single evoked action potential activated electrical activity in at least a dozen different neurons, some of which were identified. This electrical activity was characterized by a high degree of temporal and spatial variability. The action potentials of coactivated neurons, i.e. activated by the same mechanosensory neuron, did not show any significant pairwise correlation. Indeed, the analysis of evoked action potentials indicates clear statistical independence among coactivated neurons, presumably originating from the independence of synaptic transmission at distinct synapses. This statistical independence may be used to increase reliability when neuronal activity is averaged or pooled. It is suggested that statistical independence among coactivated neurons may be a usual property of distributed processing of neuronal networks and a basic feature of neural computation.

[Epidural spinal stimulation in the treatment of refractory angina pectoris. Its clinical efficacy, complications and long-term mortality. An Italian multicenter retrospective study]. / La stimolazione spinale epidurale nel trattamento dell'angina pectoris refrattaria. Efficacia clinica, complicanze e mortalità a lungo termine. Studio retrospettivo multicentrico Italiano.

BACKGROUND: Spinal cord stimulation has been used for many years in the treatment of refractory angina pectoris. Its anti-anginal and anti-ischemic effect has been well documented in several studies, but the long-term efficacy, safety and survival rate are not well known. The aim of this study was to carry out a retrospective analysis of a series of patients from the Italian Multicenter Registry, the data of which were collected in five centers, by means of a questionnaire. METHODS: One hundred and thirty patients (83 males, 47 females, mean age 74.8 +/- 9.8 years) were submitted to spinal cord stimulator implantation for refractory angina pectoris in the period 1988-1995 and controlled during a mean follow-up of 31.4 +/- 25.9 months. A previous myocardial infarction had already occurred in 69.3% of patients, whereas in 67.6% multivessel coronary artery disease was documented. A left ventricular dysfunction (ejection fraction < 0.40) was present in 34% of patients; bypass surgery and coronary angioplasty were performed in 49.6% and in 27% of patients respectively. In 96.3% of cases revascularization procedures were not advisable. RESULTS: A complete follow-up of 116 patients (89.2%) was available. The spinal cord stimulator induced a significant reduction in NYHA functional class from 2.5 +/- 1.2 to 1.5 +/- 0.9 (p < 0.01). During the follow-up 41 patients (35.3%) died, and in 14.2% a new acute myocardial infarction developed. The total percentage of minor spinal cord stimulation-related complications was 6.8%. No major complications occurred. The annual total mortality rate was 6.5%, whereas the cardiac mortality rate was 5%. Compared to the survivors, patients who died showed a higher incidence of left ventricular dysfunction, previous myocardial infarction and bypass surgery at implantation. CONCLUSIONS: In our experience, spinal cord stimulation is an effective therapy in patients affected by refractory angina pectoris and who cannot undergo revascularization procedure. The complication rate is low, with the total and cardiac mortality showing a trend as that reported for patients with similar coronary disease.

Properties of the evoked spatio-temporal electrical activity in neuronal assemblies.

Properties of neural computation were studied in two types of neuronal networks: isolated leech ganglia and neuronal cultures of dissociated cortical neurons from neonatal rats. With appropriate experimental set-ups it was possible to obtain a precise description of the spread of excitation induced by specific inputs. The evoked spatio-temporal electrical activity was characterized by large variability and the electrical activity of neurons activated by the same stimulation was found to be statistically independent to a high degree. The variability presumably originates from basic properties of synaptic transmission, which is stochastic in nature. As a consequence, the large variability of the evoked spatio-temporal electrical activity appears to be a general property of neural computation and a typical feature of neuronal assemblies. It is shown, however, that the observed statistical independence of co-activated neurons may be used to reduce the effects of variability by appropriately averaging or pooling the electrical activity.

[Effects of spinal cord stimulation on regional myocardial blood flow in patients with refractory angina. A positron emission tomography study]. / Effetti della stimolazione spinale epidurale sul flusso miocardico regionale in pazienti con angina pectoris refrattaria. Uno studio con tomografia ad emissione di positroni.

BACKGROUND: Spinal cord stimulation (SCS) is an alternative therapy in patients with refractory angina pectoris when coronary revascularization cannot be performed. Several hypotheses have been given to explain the effects of SCS in reducing the number and the intensity of anginal crises. These hypotheses include possible variations in myocardial blood flow (MBF). The aim of our study was to assess regional MBF in a group of patients with spinal cord stimulator, using positron emission tomography (PET). METHODS: We studied 15 patients (9 male and 6 female), mean age 74 +/- 7 years, who were carriers of a spinal cord stimulator implanted 17 +/- 14 (range 1-48) months before. All patients had been affected with angina pectoris that was refractory to maximal tolerated pharmacological therapy. Eight patients had had a previous myocardial infarction and four patients had undergone a revascularization procedure. Every patient underwent two PETs with nitrogen-13-ammonia as the perfusion tracer. The first one was performed with the stimulator switched off for at least 20 hours, and the second one with the stimulator switched on for at least 4 hours. The quantitative evaluation of regional MBF (anterior, inferior, lateral, septal walls and apex) was performed with Patlak graphic analysis. The normal value of basal MBF in our laboratory is 0.6-1 ml/min/g. RESULTS: The mean value of MBF increased from 0.72 +/- 0.33 ml/min/g with the stimulator off, to 0.80 +/- 0.33 ml/min/g with it on (p = 0.004). An increase in regional myocardial perfusion, with the stimulator on as opposed to off, was observed in 47 (62%) of the 75 regions studied. With the stimulator on, in comparison with off, the value of MBF increased from 0.45 +/- 0.11 ml/min/g to 0.56 +/- 0.19 (p = 0.0001) in the 35 regions with low basal MBF (< 0.6 ml/min/g), and from 0.77 +/- 0.14 ml/min/g to 0.92 +/- 0.29 ml/min/g (p = 0.013) in the 23 regions with basal MBF between 0.6 and 1 ml/min/g. Instead, in the 17 regions with high basal MBF (> 1 ml/min/g) it decreased with the stimulator on instead of off, going from 1.22 +/- 0.20 to 1.13 +/- 0.22 ml/min/g (p = 0.112). CONCLUSIONS: Our study suggests that the beneficial effects of SCS in refractory angina may also be related to an increase in mean MBF and to a redistribution of MBF between the regions with low or normal basal flow and the regions with high basal flow.

Gastric Peristalsis Control by Mono Situ Electrical Stimulation: a Preliminary Study.

BACKGROUND: This study was initiated 3 years ago when antral gastric stimulation was first used successfully to reduce free feeding in swine. METHODS: Three swine weighing 45 kg each were implanted with one subserosal bipolar electrode, positioned in the antrum, close to the pylorus, at the anterior side of the lesser gastric curvature. RESULTS: During 4 hours of kethamine anesthesia we paced the stomach by various patterns of electrical stimulation and obtained both forward and backward peristalsis, as well as gastric peresis. CONCLUSION: Variations in antral electrical stimulation produce characteristic patterns of forward and reverse peristalsis.

Long-term Effects of Gastric Pacing to Reduce Feed Intake in Swine.

BACKGROUND: The purpose of this study was to show the effect of chronic antral gastric electrical stimulation on the feeding behavior of swine. METHODS: Three groups of swine were investigated; first group control-group, second group- 8 months of electrical antral stimulation (10 Volts; 450 micros; Hertz 100; Mode: Cycling; on time 3.25 s; off time 5.15 s), the third group- 3 months of stimulation with modification of the following parameters- amplitude 8 Volts, Hertz 5. All animals were nourished with a commercial balanced dry feed ad libitum. RESULTS: Group one demonstrated continued increased weight gain. After 90 days of stimulation, group two noted a net decrease of food intake from 12% to 16%, followed by a net cyclical weight loss 30 days later (2 weeks of weight gain followed by 1 week of weight loss). The percentage difference between group one and two in increasing weight was- 12 to 29% respectively. The feed output of the stimulated group (group two) was 12.8 less compared with the control. Finally, group three was used to test a lower stimulation rate, resulting in a shorter rest during feeding and a 7% increase in consumption compared with control. CONCLUSIONS: Long-term antral gastric pacing influences the alimentary behavior of swine. We attempt to extrapolate this influence in humans for possible attendant applications in patients with consumption dysfunction (e.g. bulimia and/or anorexia).

[Postoperative pain in pediatric patients]. / Il dolore post-operatorio nel paziente pediatrico.

Surgery is an unpleasant experience which is always related to a period of pain. In the pediatric patient this results in an important effective and metabolic-neuroendocrine manifestation. After a short review of the methods recently used to evaluate pain-qualitatively as well as quantitatively, we focused on the different techniques and drugs which can be used by the anesthesiologist to achieve an adequate control of the pain symptoms. The aim is to provide devices which can be used for different groups of age in order to guarantee the maximum efficacy in pain control with the least side effect and invasiveness.