Spontaneous burst-firing in three auditory cortical fields: its relation to local field potentials and its effect on inter-area cross-correlations.

Burst-firing refers to epochs of sharply elevated neural discharge. It has been suggested that correlated firing in different cortical areas in anesthetized animals results from spontaneous burst-firing related to electroencephalogram spindling activity and state of drowsiness. To investigate this, simultaneous recordings of spontaneous firings of neurons in the primary (AI), secondary (AII) and anterior (AAF) fields of the auditory cortex in the lightly anaesthetized cat were obtained. This allowed a study of bursting behavior in the three cortical areas under exactly the same anesthetic state. Burst occurrences were detected using the Poisson-surprise method, and were typically highly synchronized with local field potentials (LFPs) and with burst-firing of other neurons recorded on the same electrode. Burst-firing occurred in 85% of 371 units studied, and in 48 (15%) thereof there were at least 100 bursts per 15 min. Neurons in Al were bursting at a significantly higher rate, but with fewer spikes per burst, than units in AII. The average percentage of the time that a spontaneously firing neuron is in the bursting state is only about 3% (range 0.004, 29%). The average peak cross-correlation coefficients between spikes and LFP triggers were largest for burst-onset spikes, followed by those between all burst spikes and LFP triggers, and smallest when all spikes of the single unit were used in the correlation. This was the case for within- and between-area conditions. Burst-onset times in different auditory fields were not correlated. Thus, the major cause of the observed correlation of spontaneous firing in different cortical areas is not synchronous burst-firing.

Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.

Dexfenfluramine was approved in the United States for long-term use as an appetite suppressant until it was reported to be associated with valvular heart disease. The valvular changes (myofibroblast proliferation) are histopathologically indistinguishable from those observed in carcinoid disease or after long-term exposure to 5-hydroxytryptamine (5-HT)(2)-preferring ergot drugs (ergotamine, methysergide). 5-HT(2) receptor stimulation is known to cause fibroblast mitogenesis, which could contribute to this lesion. To elucidate the mechanism of "fen-phen"-associated valvular lesions, we examined the interaction of fenfluramine and its metabolite norfenfluramine with 5-HT(2) receptor subtypes and examined the expression of these receptors in human and porcine heart valves. Fenfluramine binds weakly to 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors. In contrast, norfenfluramine exhibited high affinity for 5-HT(2B) and 5-HT(2C) receptors and more moderate affinity for 5-HT(2A) receptors. In cells expressing recombinant 5-HT(2B) receptors, norfenfluramine potently stimulated the hydrolysis of inositol phosphates, increased intracellular Ca(2+), and activated the mitogen-activated protein kinase cascade, the latter of which has been linked to mitogenic actions of the 5-HT(2B) receptor. The level of 5-HT(2B) and 5-HT(2A) receptor transcripts in heart valves was at least 300-fold higher than the levels of 5-HT(2C) receptor transcript, which were barely detectable. We propose that preferential stimulation of valvular 5-HT(2B) receptors by norfenfluramine, ergot drugs, or 5-HT released from carcinoid tumors (with or without accompanying 5-HT(2A) receptor activation) may contribute to valvular fibroplasia in humans.

Effect of complete and partial bilateral lesions of the deep cerebellar nuclei on amygdaloid kindling in rats.

PURPOSE: The roles of the deep cerebellar nuclei in epileptogenesis and seizure expression are not well defined. To determine their properties, we examined the effects of lesions to the dentate, fastigial, and interpositus nuclei in adult rats that were electrically kindled in the amygdaloid complex. Changes in afterdischarge duration (ADD) as well as the expression and progression of behavioral seizures to fully generalized tonic-clonic convulsions (stage 5) were assessed. METHODS: Fifty rats first underwent bilateral electrolytic lesions of either the dentate, fastigial, or interpositus nuclei. After a 7-day recovery period, they were kindled daily until they manifested two stage 5 convulsions. Careful histological examination was used to determine lesion extent. RESULTS: When the dentate or fastigial nucleus was completely destroyed on the side contralateral to the stimulated amygdala, fewer stimulations were required to produce stage 5 seizures and latencies to the expression of forelimb clonus were shorter, as were ADD. On the other hand, when the dentate or fastigial nucleus was only partly obliterated on the contralateral side, more stimulations were required to produce stage 5 seizures and ADD was longer. Neither complete nor partial lesions of the interpositus nuclei had any effect on the number of stimulations to reach a stage 5 seizure, latency to the expression of clonus, or ADD. CONCLUSIONS: Our findings suggest that the dentate and fastigial nuclei, but not the interpositus nuclei, may normally retard epileptogenesis and inhibit clonic behaviors, but paradoxically may facilitate ADD.

Post-activation potentiation in the neocortex of awake freely moving rats.

The search for the cellular processes that underlie information storage within neuronal systems lead to the development of two models of post-activation potentiation, long-term potentiation (LTP) and kindling. Both models give rise to a long-lasting increase in synaptic strength and altered unit discharge patterns. The present paper reviews synaptic plasticity in the neocortex of awake freely moving rats following both single and multiple sessions of activation with high-frequency, tetanic electrical stimulation. The phenomenology of neocortical post-activation potentiation and some possible underlying mechanisms are discussed. We speculate that the functional significance of potentiated responses may reflect a reorganization of the neocortex in a manner similar to those that create and define receptive fields.

Use of fluoxetine for the treatment of stereotypical pacing behavior in a captive polar bear.

Stereotypical behaviors are common in captive animals, particularly captive polar bears. Effects of oral administration of fluoxetine on chronic stereotypical and typical behaviors in a captive polar bear were monitored. Fluoxetine treatment terminated stereotypic pacing behavior, facial tic, and huffing/coughing activity. The expression of typical polar bear behaviors was not affected by fluoxetine treatment, although the proportion of time spent engaged in typical behaviors changed during the course of the observation period. Response of the bear to fluoxetine treatment indicated that pharmacologic manipulation of the serotonergic system can safely eliminate stereotypical behaviors in captive polar bears.

Arrest of seizure progression during electrical kindling in guinea-pigs with prior pentylenetetrazol-induced convulsions.

A number of comparative differences in the kindling phenomenon have been observed between guinea-pigs and rats. These differences likely reflect different mechanisms underlying brain plasticity. In this study, guinea-pigs were used to examine the kindling transfer phenomenon between peripheral pentylenetetrazol injection and electrical kindling of the amygdala. The changes in afterdischarge characteristics and behavioural seizures during electrical kindling were compared between animals that had experienced three PTZ-induced convulsions and PTZ-naive controls. We report that on the first electrical kindling session the PTZ-convulsed guinea-pigs displayed lower AD thresholds, enhanced AD durations and seizures, but that their seizures did not progress with repeated daily kindling stimulation.

Evolution of afterdischarge and seizure characteristics during electrical kindling of the guinea-pig.

Interspecies comparisons may help us understand the mechanisms which underlie brain plasticity. In this study, we examined the electrical kindling phenomenon in the amygdala, piriform and perirhinal regions of the guinea-pig. The changes in afterdischarge (AD) characteristics and behavioural seizures were assessed under different stimulation intervals and parameters as well as under reduced inhibitory neurotransmitter systems. We report that the guinea-pigs displayed a number of similarities with other species, such as the progressive increases in AD characteristics and seizure behaviours, but also a number of differences, such as the behavioural manifestations of the seizures, failing to reach a fully generalized tonic-clonic seizure and an apparent insensitivity to both low-frequency stimulation and reduced GABA and catecholamine levels.

Coronary angioplasty for chronic total occlusion reduces the need for subsequent coronary bypass surgery.

Coronary angioplasty was performed in 44 consecutive patients with total occlusion that lasted longer than 1 week. The primary success rate was 59%. Angiographic restudy in 25 of the 26 successful patients (96%) revealed restenosis in 17 patients (65%), which was asymptomatic in seven (44%). Significant correlates of restenosis were mean luminal stenosis at the conclusion of the procedure and symptom recurrence. Clinical follow-up at a mean of 31 +/- 12 months revealed that coronary artery bypass surgery was more frequent in patients who had an unsuccessful initial angioplasty procedure (7/18 vs 3/26; p = 0.04). Nine patients (35%) who had an initially successful procedure required a second angioplasty for symptomatic restenosis. Angioplasty for totally occluded coronary arteries has a high incidence of restenosis that is often asymptomatic. This procedure can, however, lead to a reduction in the need for coronary artery bypass surgery for symptom control.

Determinants of restenosis and lack of effect of dietary supplementation with eicosapentaenoic acid on the incidence of coronary artery restenosis after angioplasty.

The effect of an eicosapentaenoic acid-rich encapsulated preparation of fish oil on the incidence of early restenosis after coronary angioplasty was assessed by a randomized double-blind placebo-controlled study. A total of 108 patients received either 10 capsules of fish oil (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid) or 10 control capsules (50% olive oil, 50% corn oil), commencing the day before angioplasty and continuing for 4 months after angioplasty, in addition to treatment with aspirin and verapamil. In 101 (94%) of the 108 patients, follow-up angiographic or postmortem result was evaluated at a mean (+/- SD) of 100 (+/- 22) days. Angiographic restenosis was observed in 34% of patients (29% of lesions) in the fish oil-treated group and 33% of patients (31% of lesions) in the control group (no significant difference). The overall incidence of angiographic restenosis was significantly higher in patients with 1) recurrent angina pectoris, 2) a positive exercise test at follow-up after angioplasty, 3) residual stenosis greater than 30% immediately after angioplasty, and 4) dilation of the left anterior descending or right coronary artery. Biochemical investigations showed a greater decrease in the serum triglyceride levels in the fish oil-treated group versus the control group (p less than 0.05) but no differences between the two groups in cholesterol levels or platelet counts over the 4 month period. In conclusion, in this study, the administration of fish oil at a dose of 10 capsules/day did not reduce the incidence of early restenosis after coronary angioplasty.

Long-term clinical and angiographic results following percutaneous transluminal coronary angioplasty.

The long-term results of percutaneous transluminal coronary angioplasty were evaluated in our first 42 patients, who had initial successful angioplasty and no restenosis on angiogram performed four months after angioplasty. Evaluation included repeat follow-up angiogram performed approximately two years after angioplasty in 22 of the 42 patients. All 42 patients had single vessel disease with severe angina pectoris refractory to medical treatment before angioplasty; at a mean follow-up of 28 months after angioplasty, 37 (88%) were asymptomatic. No patient died or underwent coronary artery bypass graft surgery during the follow-up period, although three patients (7%) suffered a myocardial infarction due to occlusion of a nondilated artery. In the 22 cases studied at a mean of 28 months after angioplasty, angiogram showed that successful coronary artery dilatation remained in all cases, with no deterioration of a dilated lesion between the four and 28 month angiograms. Progression of atherosclerosis, however, did occur in five of the 22 patients (23%), with development of either stenosis or occlusion of a non-dilated vessel. This study suggests that the development of restonsis between four and 28 months after percutaneous transluminal coronary angioplasty is unlikely. The results suggest an excellent long-term prognosis after angioplasty, in patients who have no evidence of restenosis at four months after an initially successful dilatation.

Balloon dilatation of coronary arteries. Four years' experience of coronary angioplasty.

The results of 126 consecutive balloon dilatations of coronary arteries, carried out in 110 patients between 1980 and the end of 1983, are reported. The follow-up periods ranged from one to 47 months. The primary success rate was 74%, and the long-term success rate was 65%. In successful cases, the diameter of stenosis was changed, on average, from an initial 88% to 33%. Acute occlusion of the vessel occurred on 13 occasions (10%). Of these, myocardial infarction occurred in eight (6%), and emergency bypass grafts were performed in nine (7%). One of these 13 patients died (case fatality rate, 0.8%). Occlusion of the dilated vessels did not occur after the patients were discharged from hospital. However, stenosis recurred in 20 of 80 patients with successfully dilated arteries (25%). Dilatation was repeated in 16 of these, and stenosis had not recurred at the three-months' follow-up. There has been a marked improvement in the success rate of this procedure over the years. It is concluded that balloon dilatation is an effective and safe alternative to bypass graft surgery in selected patients with coronary artery disease.

Recent concepts in the management of ischaemic cardiac syndromes.

Ischaemic heart disease is the most important cause of death in our society. Knowledge of the natural history of the various ischaemic syndromes leads to better management, with emphasis on prevention of cardiac necrosis rather than management of its sequelae. This article is from the Department of Cardiology, Royal Melbourne Hospital.