Release of [3H]5-hydroxytryptamine from the intermediate area of rat thoracic spinal cord is modulated by presynaptic autoreceptors

Serotonin (5-HT) nerve terminals innervate sympathetic preganglionic neurons of the intermediolateral cell column (IML); however, neither the depolarization-induced release of 5-HT nor the presence of presynaptic modulatory autoreceptors have been directly studied in this system. We used in vitro superfusion of the microdissected intermediate area (including the intermediolateral cell column, intercalated nucleus, and central autonomic nucleus) of the rat thoracic spinal cord to measure basal and stimulated release of preloaded [³H]5-HT. Elevated K⁺ evoked a concentration- and Ca²⁺ dependent release of [³H]5-HT. Exogenous 5-HT and the 5-HT_1B agonist, CGS-12066B, both decreased the K⁺-stimulated release of [³H]5-HT. A 5-HT_1B antagonist (methiothepin) blocked the 5-HT- and the CGS-12066B-induced inhibition of K⁺-evoked release of [³H]5-HT. A 5-HT_1A antagonist (NAN-190) did not alter the inhibitory actions of exogenous 5-HT. Moreover, a 5-HT_1A agonist (8-OH-DPAT), a 5-HT_2A/2C agonist [(+/-)-DOI hydrochloride], and a 5-HT₃ agonist (2-methyl-5-HT) did not alter the K⁺ evoked release of [³H]5-HT. These data demonstrate that 5-HT is released from the intermediate area of the rat thoracic spinal cord. The 5-HT receptor subtype involved in the inhibition of the evoked release of [³H]5-HT is of the 5-HT_1B subtype. These findings may help clarify the complex role of 5-HT in spinal regulation of the sympathetic nervous system. © 1994 Wiley-Liss, Inc

1 This article is US Government work and, as such, is in the public domain in the United States of America.

     

Observations on the arterial baroreflex in neurally mediated vasodepressor syncope

The arterial baroreflex was studied in subjects who had recently had an episode of vasodepressor syncope. This was determined using 2–3 mcg/kg intravenous boluses of phenylephrine and assessing the bradycardic response. The values were measured in ms/mmHg and expressed as the angular coefficient of the regression line between the increase in R—R interval on the electrocardiograph and the systolic arterial pressure. In subjects examined immediately after the vasodepressor syncope episode the bradycardic response was much more marked than in controls (p < 0.01) and in the subjects themselves 6 months after the episode, provided that they were symptom-free (p < 0.01). It is concluded that in vasodepressor syncope there is a phase in which the baroreflex is highly sensitive and that this is due not to a lowering of the stimulation threshold but to a gain in the efferent arc, which explains a vagotonic response.     

Monitoring during paediatric cardiac anaesthesia

Monitoring of paediatric anaesthesia has become increasingly more complex in recent years and this is particulary true of cardiac anaesthesia. The purpose of this review is to give a comprehensive update of published material related to both routine and specialized cardiac monitoring. Routine monitoring can be particularly affected by the alterations of cardiac rhythm, blood flow, cardiac output and oxygenation which result from the congenital heart abnormalities themselves, the type of surgery undertaken and the effects of cardiopulmonary bypass. The use of specialized monitoring is becoming more widespread, particularly in the areas of cerebral function, mixed venous oxygenation, cardiac output measurement and coagulation. In the last five years, with the development of smaller probes, a great deal has been published on transoesophageal echocardiography. The use of the current monitors of cerebral function still remains controversial despite the need for a monitor of adequate brain perfusion, reflecting the need for a great deal of further research in this area. This review will concentrate on particular areas which have seen the most profound changes and on monitoring that may form the standards of tomorrow. Finally, amongst all the technology, it should not be forgotten that the most important clinical monitor is the bedside clinical monitoring of the physicians themselves. Depuis quelques années, le monitorage de l’anesthésie pédiatrique devient déplus en plus complexe et tout particulièrement en anesthésie cardiaque. L’objectif de ce travail consiste à passer en revue la littérature actuelle qui traite du monitorage usuel et spécialisé. Le monitorage usuel peut être influencé par les modifications de la fréquence cardiaque, du courant sanguin, du débit cardiaque et de l’oxygénation provoqués par les anomalies cardiaques congénitales, du type de chirurgie et des retentissements de la circulation extracorporelle. L’utilisation du monitorage spécialisé est de plus en plus répandu et concerne particulièrement la circulation cérébrale, l’oxygénation du sang veineux mêlé, la mesure du débit cardiaque et la coagulation. Au cours des cinq dernières années, le développement de sondes plus petites a généré de nombreuses publications sur l’échocardiographie transoesophagienne. L’utilisation des moniteurs actuels de la fonction cérébrale demeure sujet à controverse bien qu ’un moniteur de perfusion cérébrale adéquat demeure toujours aussi essentiel, confirmant ainsi le besoin de recherches supplémentaires sur ce sujet. Ce survol se portera spécialement sur les champs d’activités qui ont connu les changements les plus profonds et sur le monitorage qui établira les standards du futur. Finalement, au milieu de cette technologie, il ne faut jamais oublier que le moniteur clinique le plus important se trouve au chevet du malade en la personne du médecin.     

Technetium-99m dimercaptosuccinic acid and ifosfamide tubular dysfunction in children with cancer

Quantitative ^99mTc-dimercaptosuccinic acid (^99mTc-DMSA) renal scintigraphy was used to asses ifosfamide-induced changes in renal function in 11 children who received chemotherapy for various malignancies. Serial measurements of absolute ^99mTc-DMSA renal uptake, calculated on conjugated views, were performed during and after chemotherapy. Data of 37 studies obtained before and at different cumulative dose levels of ifosfamide were analysed in relation to clinical and biochemical parameters. A highly significant relationship between ^99mTc-DMSA uptake and cumulative ifosfamide dose was found (P<0.001). The most frequently observed abnormal pattern on scintigraphic images was decreased kidney uptake together with increased accumulation in bladder. ^99mTc-DMSA uptake was more consistent than ₂-microglobulin values in urine and more sensitive than quantitative hyperaminoaciduria and tubular resorption of phosphate for the detection of ifosfamide-induced tubular dysfunction. ^99mTc-DMSA uptake was decreased in both patients with and patients without clinical toxicity. Persistently reduced ^99mTc-DMSA uptake was observed in four patients during follow-up; in one of them, who was asymptomatic after ifosfamide therapy, sudden onset of Fanconi syndrome was observed when he was retreated with carboplatin 1 year later. It is concluded that ^99mTc-DMSA renal scintigraphy is a suitable method to assess progressive ifosfamide-induced tubular injury whereas scintigraphic imaging is helpful for interpreting renal uptake changes. The test is able to detect subclinical injury and may potentially predict high risk at retreatment.     

Left ventricular dysfunction during exercise in patients with angina pectoris and angiographically normal coronary arteries (syndrome X)

Left ventricular function during exercise and recovery was investigated in patients with angina pectoris, ST segment depression during exercise and angiographically normal coronary arteries (syndrome X) using a continuous left ventricular function monitor with cadmium telluride detector (CdTe-VEST). Fourteen patients with syndrome X and 14 patients with atypical chest pain without ST segment depression during exercise and normal coronary arteries (control group) performed supine ergometric exercise after administration of 740–925 MBq of technetium-99m labelled red blood cells, and left ventricular function was monitored every 20 s using CdTe-VEST. Left ventricular ejection fraction (EF) response was impaired (55% increase from rest to peak exercise) in 11 or 14 patients with syndrome X but in none of the control patients. Resting EF was similar in the two groups (62.1%±6.7% in patients with syndrome X, 61.9%±6.2% in controls); however, EF increase from rest to peak exercise was lower in syndrome X (–3.1±9.5% vs 14.7%±7.4%, P <0.001). After cessation of exercise, all patients showed rapid EF increase over baseline and this EF overshoot was lower (19.3%±8.3% vs 26.4%±7.3%, P <0.001) with the time to EF overshoot longer (114±43 s vs 74±43 s, P<0.05) in patients with syndrome X. Thus, in patients with syndrome X, left ventricular dysfunction was frequently observed during exercise in spite of normal epicardial coronary arteries. Correspondence to: J. Taki     

Motility Disorders after Roux-en-Y Gastrojejunostomy

About 30% of patients who have a Roux-en-Y gastrojejunostomy after gastrectomy suffer from abdominal pain, nausea, vomiting of food and bloating made worse by eating. This syndrome, called the Roux stasis syndrome, is caused, in part, by a motility disorder of the Roux limb. Transection of the jejunum during the construction of the limb separates the limb from the natural small intestinal pacemaker located in the duodenum. Ectopic pacemakers then appear in the limb and trigger retrograde contractions in its proximal portion. These contractions slow transit through the limb and result in Roux stasis. Current nonsurgical treatment of the syndrome includes the use of prokinetic agents and intestinal pacing, neither of which has demonstrated long-term benefits. A near-total gastrectomy may speed upper gastrointestinal transit somewhat, but stasis in the Roux limb often persists. Our current approach aims at preventing the syndrome by the use of an ‘uncut’ Roux limb, an operation which preserves myoneural continuity between the duodenal pacemaker and the Roux limb and so prevents the appearance of ectopic pacemakers and stasis in the limb.     

Good exercise capacity at hospital discharge predicts recovery of baroreflex sensitivity after myocardial infarction

Myocardial infarction results in depressed baroreflex sensitivity,which has been shown to be associated with increased risk ofventricular arrhythmias and sudden death. We measured baroreflexsensitivity in 37 patients with acute myocardial infarctionbefore hospital discharge and 3 months after the infarctionto find out whether the baroreflex sensitivity recovers duringthat period. In addition, baroreflex sensitivity was assessedin 15 healthy controls. Baroreflex sensitivity was assessedfrom the regression line relating the change in R-R intervalto the change in systolic blood pressure following an intravenousbolus injection of phenylephrine. There was a wide inter-individualvariation in the change of baroreflex sensitivity (Abaroreflexsensitivity) in infarction patients, but the average baroreflexsensitivity showed no significant change during the 3-monthfollow-up (10.2 +5.6 to 11.8 ± 7.5 ms. mmHg ^–1,ns) and remained lower than the baroreflex sensitivity of thecontrols (16.4 ± 9.7 ms. mmHg^–1, P<0.05). Baroreflexsensitivity correlated significantly with exercise capacitymeasured before hospital discharge. When the patients were dividedinto tertiles according to the baroreflex sensitivity ( –3.3 ± 1.5 ms. mmHg^–1 in the lowest tertile, 1.0± 1.0 ms. mmHg^–1 in the middle tertile and 7.5± 40 ms. mmHg^–1 in the highest tertile) the exercisecapacity was found to increase from the lowest to the highesttertile (exercise time 357 ± 115 s, 418 ± 126s and 461 ± 141 s, respectively; P<0.05 lowest vshighest tertile). Patients with a low exercise tolerance (exercisetime <360 s) showed a significantly smaller Abaroreflex sensitivitythan patients with a good exercise tolerance (exercise time480s) ( – 0.5±4.4 vs 5.3 ± 5.4ms. mmHg^–1,P<0.05), respectively. Baroreflex sensitivity was not relatedto the location or type of infarction, thrombolytic therapy,presence of angina pectoris or left ventricular function atthe time of discharge. In conclusion, exercise capacity assessedbefore hospital discharge seems to be a predictor of baroreflexsensitivity recovery in patients with a recent myocardial infarction.     

Pulmonary venous flow as assessed by Doppler echocardiography: potential clinical applications

During the past few years Doppler assessment of pulmonary venous flow has gained increasing interest. The growing experience with the use of transesophageal echocardiography, the approach that nearly always yields registrations adequate for quantitative analysis, has markedly contributed in this respect. The Doppler-derived pulmonary venous flow pattern can be regarded as a measure of left atrial inflow and it augments the clinical significance of Doppler transmitral flow in the evaluation of diastolic left ventricular function. This article summarizes physiological background, possible applications, and limitations of Doppler echocardiography of pulmonary venous flow in clinical cardiology.     

The assessment of left ventricular filling dynamics using an online automatic border detection algorithm: comparison with cineventriculography

An echocardiographic system has been developed that performs automatic endocardial border detection and instantaneously calculates and displays a waveform of left ventricular cavity area versus time. The purpose of this study was to compare measurements of left ventricular filling dynamics from automatic border detection echocardiography with similar measurements from cineventriculography. Thirty-three patients undergoing cardiac catheterization had automatic border detection echocardiography performed within 45 minutes of cineventriculography. Ten patients had normal catheterization findings and 23 had cardiac disease. The automatic border detection waveforms generated from two echocardiographic views were measured to determine the fraction of filling occurring during the early diastolic rapid filling phase and during the filling phase resulting from atrial contraction. Similar fractions were derived from curves generated from frame-by-frame measurements of cineangiographic volumes. Results were analyzed by correlating echocardiographic and cineventriculographic results, and by a limits of agreement analysis (limits of agreement were +/- 2 standard deviations of the mean difference between echocardiography and cineventriculography). There were significant correlations between echocardiography and cineventriculography for each of the parameters studied. The best results were obtained for the apical four-chamber view (rapid filling fraction r = 0.72, P < 0.0001, atrial filling fraction r = 0.56, P < 0.001). Differences in filling patterns between normal and abnormal patient groups detected by cineventriculography were also detected by automatic border detection echocardiography. However, broad limits of agreement were observed, that may limit the ability of the automatic border detection system to reliably predict cineventriculographic results in an individual patient. Automatic border detection echocardiography can provide information about left ventricular filling dynamics that is similar to that obtained from frame-by-frame analysis of cineventriculograms. However, the variability in the results may limit the application of the technique in individual patients.     

Prevalence of diabetes mellitus and impaired glucose tolerance in parents of women with gestational diabetes

Summary Nuclear families of non-insulin-dependent diabetic (NIDDM) patients are uncommon, as usually one or both parents have died. In order to aid identification of complete nuclear families, we have ascertained the disease process at a younger age by studying subjects with previous gestational diabetes. One hundred women who had had gestational diabetes, age (±SD) 38 (6) years, were screened by fasting plasma glucose (fpg). Sixty-one were found to have either fasting hyperglycaemia (5.5fpg<7.8 mmol/l) or diabetes. Of these women 35 had both parents alive and the parents of 14 of these women agreed to the assessment of their metabolism by a continuous infusion of glucose with model assessment (CIGMA). Seven probands had impaired glucose tolerance (IGT) and seven were diabetic. They were age 35 (4) years and had body mass index (BMI) 26 (5) kg/m². The parents were aged 62 (6) years and had BMI 29 (6) kg/m² and their affection status was defined as presence of glucose intolerance (fpg or post-infusion achieved plasma glucose level >2 SD of an age and obesity matched population). In the 14 families, five probands (36%) had neither parent affected, six (43%) had one parent affected and three (21%) had both parents affected. Only three probands had a parent with diabetes as defined by World Health Organisation criteria. We concludes that the study of women who have had gestational diabetes allows detection of probands with diabetes or impaired glucose tolerance, who have both parents available for study. A substantial proportion had neither parent affected with impaired glucose tolerance or diabetes, similar to the nuclear families of NIDDM patients. The results are in accord with studies of nuclear families of NIDDM patients in suggesting polygenic inheritance or environmental influences rather than autosomal dominant inheritance with high penetrance.Abbreviations IGT Impaired glucose tolerance - GTT glucose tolerance test - NIDDM non-insulin-dependent diabetes mellitus - fpg fasting plasma glucose - apg achieved plasma glucose - CIGMA continuous infusion of glucose test - BMI body mass index