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Sympathetic activation and tachycardia in lipopolysaccharide treated rats are temporally correlated and unrelated to the baroreflex.

The goal of this study was to investigate the sustained sympatho-excitation which occurs in sepsis and which accompanies the fall in blood pressure and to analyze its time-correlation with heart rate and the role of the baro-chemoreflexes. Rats anesthetized with pentobarbital were treated with lipolysaccharide (LPS) 20 mg/kg/20 min i.v. and mean blood pressure (MBP), heart rate (HR), rectal temperature and renal sympathetic nerve activity (RSNA) were recorded. LPS induced a fall in blood pressure, an increase in HR (+20%) and RSNA (+355%); the arterial PO2 and PCO2 remained stable and the injection was fatal within 4 h. Baroreceptor and chemoreceptor denervation accelerated the fall in MBP but did not change the survival time. Under those conditions; RSNA excitation was slightly more pronounced. During treatment with gallamine and under artificial respiration to avoid possible respiratory changes through the chemoreflex pathway, the effects of LPS remained, except for a decrease in arterial PO2. Electrolytic lesioning of the nucleus tractus solitarius or blocking the effects of baroreflex efferents by either an alpha1 or alpha2-adrenoceptor antagonists failed to alter the effects of LPS. After treatment with a beta-adrenoceptor antagonist, LPS increased RSNA but not HR and the survival time of the rats shortened. LPS administered i.c. (1 mg/kg) induced, with a short latency, effects comparable to those produced by i.v. injection. Surprisingly, the time correlation between RSNA and HR rhythms persisted when MBP dropped after LPS and moreover it reappeared in baroreceptor denervated rats after LPS. Thus under these conditions of altered baroreflex pathway and LPS induced sympathetic activation, the sympathetic output from the medulla appears to play a role in the correlation between heart rate and sympathetic nerve activity. These data indicate that the marked RSNA activation and the tachycardia are correlated and that the baroreflex and chemoreflex are not inhibited during sepsis but appear to be of minor importance in the sympathetic activation and in the blood pressure modifications.

Adrenergic alpha-Antagonists↗

Profound but transient deficits in learning and memory after global ischemia using a novel water maze test.

The pyramidal CA1 neurons of the hippocampus are critically involved in spatial learning and memory. These neurons are especially vulnerable to cerebral ischemia, but in spite of this, it has been consistently difficult to show any learning and memory deficits in two-vessel occlusion models of global ischemia. Transient global ischemia was induced in adult male rats under general anaesthesia administered by artificial respiration to prevent respiratory arrest. Systemic blood pressure was reduced to below 50 mmHg by instant adjustments of the halothane concentration, before and during bilateral occlusion of the carotid arteries. Cerebral blood flow was monitored by laser-Doppler flowmetry. Dying neurons were detected by TUNEL at 14 days after ischemia and surviving neurons by NeuN at 14 and 125 days after ischemia. Learning and memory was assessed in a novel water maze with three successive left-right choices. Transient global ischemia produced a profound and selective degeneration of CA1 neurons at 14 days after ischemia. This degeneration was associated with severe impairments in learning at 13 days after ischemia and in memory, as tested 24 h afterwards. At 125 days after ischemia, there was no significant learning and memory impairment, whereas the number of CA1 neurons was increased. These results show that transient global ischemia induced by two-vessel occlusion may lead to severe, but transient, impairments in learning and memory using a novel water maze, and that restored learning and memory is associated with an increased number of CA1 neurons.

Analysis of Variance↗

The prevention and management of perioperative complications.

The most important issues in perioperative complications of oesophagectomy are prevention, early detection and appropriate management. Anastomotic leakage is the most frequent technical surgical complication. Prevention comprises avoidance of tension or impaired vascularization of the conduit and meticulous suture technique. Management includes early diagnosis, conservative treatment or endoscopic stenting of contained leakage, and re-operation of non-contained insufficiency. All other surgical complications - such as bleeding, tracheobronchial lesions or chylothorax - are rare and warrant special therapeutic modalities. The main general non-surgical complication is postoperative pneumonia, which should be prevented by effective pain control (especially peridural catheter) and appropriate techniques of artificial respiration. Special attention should be offered to postoperative tachyarrhythmias and alcohol withdrawal syndrome. Prevention of complications also includes exclusion of patients with high operative risk based on scores and specific preoperative treatment of risk factors.

Adenocarcinoma↗

A case of acute encephalitis with refractory, repetitive partial seizures, presenting autoantibody to glutamate receptor Gluepsilon2.

An 11-year-old male was admitted to our hospital because of high-grade fever, repetitive seizures, and prolonged impairment of consciousness (Glasgow coma scale E1, M5, V1). His seizures were repetitive complex partial seizures that expanded from the unilateral face to the corresponding side of the body. He sometimes developed secondary generalized seizures. While most seizures lasted 1 or 2 min, intractable seizures also frequently (about 5 times/h) occurred. We diagnosed him as encephalitis/encephalopathy, and treated him with artificial respiration, thiamylal sodium, mild hypothermia therapy, steroid pulse therapy, massive gamma-globulin therapy, etc. Afterwards, he had sequelae, such as post-encephalitic epilepsy (same seizures continued to recur), hyperkinesia, impairment of immediate memory, change in character (he became sunny and obstinate), dysgraphia, and mild atrophy of the hippocampus, amygdala, and cerebrum. However, he could still attend a general junior high school. He was diagnosed as acute encephalitis with refractory, repetitive partial seizures (AERRPS). In this case, he was positive for autoantibody to glutamate receptor Gluepsilon2 IgG or IgM in an examination of blood and spinal fluid, and we presumed that this may have influenced his sequelae. In this case, a combination of mild hypothermia therapy, steroid pulse therapy, and massive gamma-globulin therapy was effective.

Autoantibodies↗

Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension.

The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.

Animals↗

Is high PEEP low volume ventilation in burn patients beneficial? A retrospective study of 61 patients.

In burn care lung damage by inhalation injury is a major cause of mortality in burn patients. In the field of intensive care medicine ventilation strategies to reduce lung injury caused by ventilation are under investigation. The promising results of the application of pressure controlled high PEEP low volume (HPLV) ventilation prompted us to use this ventilation strategy in our burn ICU. To establish whether this ventilation regime is beneficial the charts of 61 consecutive patients needing artificial respiration were reviewed. A scoring system for PEEP level and tidal volume was developed and treatment groups with high PEEP and low volume and low PEEP high volume regimes were compared. No statistically significant differences could be found when comparing treatment versus mortality, the number of pulmonary complications or incidence of pneumothoraces. However, the trend showed a benefit in mortality for patients with an ABSI scoring up to 9, but at the same time pulmonary complications increase. The Horovitz oxygenation index showed no advantage for the HPLV Group. In a separate analysis we found a significant correlation between absolute PEEP and mortality. The correlation between PEEP level and mortality is a dynamic factor predicting outcome, This not been described yet and can be an addition to the static ABSI score. Differences between ventilation strategies were not as evident as expected in this retrospective study, so prospective randomized studies are needed.

Adult↗

Hand assisted laparoscopic surgery of aortoiliac occlusive disease: initial results.

OBJECTIVES: Open aortobifemoral bypass grafting has been the procedure of choice for many years in patients with symptomatic aortoiliac occlusive disease (AIOD). Hand assisted laparoscopic surgery (HALS) for AIOD could have advantages like faster recovery, faster oral intake and shorter hospital stay compared to the conventional technique. We documented the results of patients who underwent HALS for AIOD in our hospitals. MATERIALS AND METHODS: from January 1999 to December 2002, 33 consecutive patients underwent HALS for AIOD. Peri- and postoperative results were prospectively registered. Three different laparoscopic approaches were applied: transperitoneal, retroperitoneal and apron approach. RESULTS: There were 23 males and 10 females, with a mean age of 59 years (range 39-85). The surgical technique applied was: transperitoneal: 22 patients, retroperitoneal: 7 patients, apron: 4 patients. Per-operative results (median) of the transperitoneal, retroperitoneal and apron approach are: operating time 240, 420 and 263 minutes, cross clamp time 32.5, 40 and 33.5 minutes, blood loss 1150, 2100 and 950 ml, respectively. Postoperatively oral intake was fully resumed in 3, 4.5 and 2 days after performing the transperitoneal, retroperitoneal and apron technique. During the ICU stay patients received artificial respiration for 0, 1 and 0 days, admission to the ICU was 0.5, 1 and 0.75 days for the transperitoneal, retroperitoneal and apron approach. Finally, hospital stay was 8, 12.5 and 7 days after the transperitoneal, retroperitoneal and apron approach. Four patients (12%) had a minor complication, 4 patients (12%) had a major complication; pneumonia with ARDS, sepsis, bypass occlusion and chylo-abdomen. No patients died. CONCLUSIONS: HALS for AIOD is a technically demanding operation with a long learning curve. All three approaches are feasible. In this series of patients, we feel the transperitoneal and apron approach have the most advantages because of the larger working space. Finally, randomized trials will determine if laparoscopic assisted or total laparoscopic aortoiliac surgery has the potential to reduce morbidity for the patient compared to the conventional technique.

Adult↗

Analytical investigations in a death case by suffocation in an argon atmosphere.

A 31-year-old engineer was found dead in a reaction vessel (diameter 0.8 m, height 1.8 m) of a bulb factory some minutes after he had entered it for repair work. Resuscitation attempts with artificial respiration were unsuccessful. Despite autopsy and usual toxicological analyses, no cause of death could be found. Since in the normal production process, argon was used as a protecting gas, the possibility of suffocation in an argon atmosphere was investigated. This was rendered more difficult because of the natural content of 0.93 vol.% argon in air and since the excessive argon could have been removed by the resuscitation attempts. Gas samples from larynx, esophagus, bronchi, and stomach, separated blood samples from both ventricles of the heart and from the vena iliaca externa as well as tissue samples from lung and liver were collected during autopsy into headspace vials in such a way that the loss of gas and a dilution by surrounding air was avoided as far as possible. The samples were analyzed by headspace GC-MS. The abundance of Ar+ (m/z = 40) was used for quantification with N2(2+) (m/z = 14) as internal standard. The following argon concentrations were measured (mean values, case under investigation/comparison cases): gas from larynx 1.79/0.96 vol.%, stomach gas 1.58/0.89 vol.%, heart blood (left ventricle) 7.2/2.7 microg/mL, heart blood (right ventricle) 5.8/2.7 microg/mL, blood from vena iliaca externa 3.6/2.7 microg/mL. A clearly increased concentration was also found in lung tissue, whereas in liver tissue no significant difference in comparison to other cases was measured. From the results, it follows that the deceased inhaled an increased amount of argon a short time before death. The concentrations are consistent with asphyxia and subsequent resuscitation attempts. They cannot be explained by a long-term inhalation of an atmosphere enriched with argon before the incident as it is likely to have occurred in this factory hall.

Administration, Inhalation↗

Sudden infant death: lingual thyroglossal duct cyst versus environmental factors.

An 8-month-old female baby was found collapsed in the prone position 30 min after being positioned under soft-bedding. She was taken to the emergency room with cardiopulmonary arrest. Her heartbeat was recovered after resuscitation and continued for 20 h under artificial respiration, at which point the child died. At autopsy, the child showed no significant pathological abnormalities apart from a thyroglossal duct cyst of 2.0 cm diameter, therefore, it seemed that the cyst, which was close to the epiglottis, had caused asphyxia through airways occlusion. However, the child had shown no respiratory problems before death, and the risk of airway occlusion as a result of lingual cysts is more likely in a supine rather than a prone position. A small amount of evidence suggested that the child died as a result of suffocation from being covered by soft-bedding, which could have caused fatal asphyxia; it is also possible that a hypoxic state induced by airway obstruction might have been enhanced by being covered with bedding. It seemed reasonable to assume that death was caused by a combination of the lingual thyroglossal duct cysts and asphyxia caused by being covered in bedding, though the main factor appeared to be the large cyst.

Airway Obstruction↗

A case of hearing loss and quadriplegia after a pontine hemorrhage.

We herein describe the case of a 50-year-old female who developed a pontine hemorrhage with consciousness disturbance and quadriplegia. Her respiratory condition was so bad that she needed to be intubated and put on artificial respiration. After her consciousness and respiratory condition gradually recovered, we noticed that she had developed a bilateral hearing loss. The auditory brain stem response test revealed only I waves on both sides, thus suggesting that her hearing loss had been caused by an injury to the hearing-conducting pathway including the cochlear nuclei. In this case, the hematoma extended from the lower to the upper part of pons and, furthermore, it was also located broadly in the dorsal part of the pons. As a result, the cochlear nuclei and corpus trapezoideum appeared to have been destroyed by the hematoma. However, since most cases with a brain stem hemorrhage showing bilateral hearing loss tend to be in a severe condition, this condition is often easy to overlook. We should therefore carefully evaluate patients' reaction to hearing stimulation to avoid overlooking any hearing loss in such patients.

Evoked Potentials, Auditory, Brain Stem↗

Impact of preoperative treatment strategies on the early perioperative outcome in neonates with hypoplastic left heart syndrome.

OBJECTIVE: This study was undertaken to determine the impact of specific intensive care procedures on preoperative hemodynamics, incidence of preoperative organ dysfunction, and in-hospital mortality among neonates with hypoplastic left heart syndrome with pulmonary overcirculation and to assess the influence of the change in preoperative management on early postoperative outcome. METHODS: In this retrospective evaluation of 72 neonates with classic hypoplastic left heart syndrome and severe pulmonary overcirculation with different preoperative management strategies from 1992 to 1995 and from 1996 to 2000, univariate and multivariate analyses of risk factors were performed with stepwise logistic regression. RESULTS: Among patients with ventilatory and inotropic support from admission until surgery, degree of metabolic acidosis (lowest recorded and prerepair pH values) was significantly higher than among patients who received systemic vasodilators without ventilation before surgery. Preoperative organ dysfunction occurred in 19 of 72 patients (26%), predominantly before 1996; the most significant was hepatic failure in 13 (68%). Lowest recorded and prerepair pH values did not predict the development of organ dysfunction, whereas inotropic medication, lack of afterload reduction, and especially ventilatory support correlated significantly with organ injury. In-hospital mortality decreased from 65% (13/20) to 13% (6/46) from the first to the second period. According to multivariate analysis, ventilatory support and organ dysfunction were significantly related to in-hospital mortality. CONCLUSION: In neonates with hypoplastic left heart syndrome, systemic afterload reduction can avoid preoperative artificial respiration, identified as a significant risk factor for the development of preoperative dysfunction of end organs and in-hospital mortality.

Cardiac Surgical Procedures↗

Visual receptive field properties of excitatory neurons in the substantia nigra.

The substantia nigra has been widely regarded as a structure involved in visuomotor co-ordination, but little is known about the sensory background of its function. Here we give a detailed description of the visual receptive field properties of excitatory substantia nigra neurons. The visual responses of 59 excitatory neurons were recorded in both the substantia nigra pars reticularis and the pars compacta of halothane-anesthetized, immobilized, artificially respirated cats. The substantia nigra neurons were not responsive or exhibited very low sensitivity to stationary visual stimulation. The units responded optimally to small stimuli moving at intermediate or high velocities in their extremely large receptive field. We observed no signs of retinotopical organization within the substantia nigra. A majority of the units exhibited narrow direction tuning and high direction selectivity, while a smaller proportion of them were broadly tuned and not direction-sensitive. Our results suggest that the visual properties of the excitatory substantia nigra units are quite similar to those of the superior colliculus and other extrastriatal structures that receive tectal afferents. This supports the notion that the substantia nigra processes dynamic visual information and that its excitatory visual neurons are modulated by the extrageniculate tectal visual system of the mammalian brain.

Action Potentials↗

The in vivo cardiovascular effects of box jellyfish Chironex fleckeri venom in rats: efficacy of pre-treatment with antivenom, verapamil and magnesium sulphate.

Using a new technique to extract venom from the nematocysts, the efficacy of CSL box jellyfish antivenom (AV) and adjunct therapies, verapamil and magnesium sulfate (MgSO(4)), were investigated against the in vivo cardiovascular effects of Chironex fleckeri venom in anaesthetised rats. C. fleckeri venom (30 microg/kg; i.v.) produced a transient hypertensive response followed by hypotension and cardiovascular collapse within 4 min of administration. Prophylactic treatment of anaesthetised rats with CSL box jellyfish AV (3000 U/kg; i.v.) did not have any effect on the venom-induced pressor response, but prevented cardiovascular collapse in four out of 10 animals. Administration of verapamil (20mM@0.25 ml/min; i.v.) either alone or in combination with AV, did not have any effect on the C. fleckeri venom-induced pressor response nor the consequent hypotension or cardiovascular collapse of animals. However, the administration of verapamil negated the partially protective effects of AV. Concurrent artificial respiration of animals with the above treatments did not attenuate the C. fleckeri venom-induced cardiovascular effects. MgSO(4) (0.05-0.07M@0.25 ml/min; i.v.) alone did not have any effect on the venom-induced pressor response nor the consequent cardiovascular collapse of animals. However, although combined AV and MgSO(4) administration could not inhibit the transient pressor effect following the administration of C. fleckeri venom, it prevented cardiovascular collapse in all animals. We show for the first time, the cardiovascular effects of a C. fleckeri venom sample free of tentacular contamination and the potential of MgSO(4) as an adjunct therapy for the treatment of potentially fatal C. fleckeri envenomings.

Animals↗

A biochemical and pharmacological examination of Rhamphiophis oxyrhynchus (Rufous beaked snake) venom.

The venom of R. oxyrhynchus, a member of the psammophiine subfamily of the colubrid assemblage, was examined for biological activity using biochemical and pharmacological techniques. Venom displayed a high protein content, a complex electrophorectic profile and PLA2 activity but no detectable proteolytic or haematological activities. In the chick biventer cervicis nerve muscle preparation, venom (1-10 microg/ml) displayed postsynaptic neurotoxic activity as evidenced by inhibition of indirect (0.1 Hz, 0.2 ms, supramaximal V) twitches and responses to exogenous acetylcholine (1 mM) and carbachol (20 microM). This inhibitory effect was poorly reversible by washing. Venom (30-50 microg/ml) caused a rapid and readily reversible inhibition of direct (0.1 Hz, 2 ms, supramaximal V) twitches of the chick biventer cervicis nerve muscle preparation without morphological changes to the muscle fibers. Venom (30-100 microg/ml) inhibited electrically-evoked (0.2 Hz, 0.3 ms, 70-100 V) twitches of the prostatic segment of the rat vas deferens. This inhibitory effect was not significantly attenuated by 8-phenyltheophylline (8-PT; 20 microM), idazoxan (1 microM), a combination of ranitidine (0.2 microM) and thioperamide (10 microM) or capsazepine (10 microM). Venom (5 mg/kg) induced hypotension with subsequent cardiovascular collapse in the anaesthetised rat. The cardiovascular collapse was prevented by artificial respiration of the animals prior to venom administration. The biological activities demonstrated by R. oxyrhynchus venom may aid in prey envenomation strategies such as prey immobilisation. This study provides further evidence that colubrid venoms are comprised of multiple components which can display a variety of actions, some of which may be novel, therefore reinforcing the largely untapped potential of colubrid venoms.

Animals↗

The in vivo cardiovascular effects of an Australasian box jellyfish (Chiropsalmus sp.) venom in rats.

Using a new technique to extract venom from the nematocysts of jellyfish, the in vivo cardiovascular effects of Chiropsalmus sp. venom were investigated in anaesthetized rats. Chiropsalmus sp. venom (150 microg/kg, i.v.) produced a transient hypertensive response (44+/-4 mmHg; n=6) followed by hypotension and cardiovascular collapse. Concurrent artificial respiration or pretreatment with Chironex fleckeri antivenom (AV, 3000 U/kg, i.v.) did not have any effect on the venom-induced hypertensive response nor the subsequent cardiovascular collapse. The cardiovascular response of animals receiving venom after the infusion of MgSO4 (50-70 mM @ 0.25 ml/min, i.v.; n=5) alone, or in combination with AV (n=5), was not significantly different from rats receiving venom alone. Prior administration of prazosin (50 microg/kg, i.v.; n=4) or ketanserin (1 mg/kg, i.v.; n=4) did not significantly attenuate the hypertensive response nor prevent the cardiovascular collapse induced by venom (50 microg/kg, i.v.). In contrast to previous work examining C. fleckeri venom, administration of AV alone, or in combination with MgSO4, was not effective in preventing cardiovascular collapse following the administration of Chiropsalmus sp. venom. This indicates that the venom of the two related box jellyfish contain different lethal components and highlights the importance of species identification prior to initiating treatment regimes following jellyfish envenoming.

Animals↗

Brain death: epidemiology and quality control of solid organ donor generation.

Successful solid organ transplant programs need effective organ procurement systems. Evaluating and maintaining the quality of an organ procurement system requires multilevel institutional coordination as well as reliable information regarding potential donors. The objective of this study was to analyze the potential to generate adult solid organ donors at a countrywide level as well as at individual hospital levels in Uruguay from 2000 to 2002. The analyzed factors included: encephalic deaths (brain deaths) officially registered by the National Bank of Organs and Tissues (BNOT), the distribution of these individuals among the intensive care units (ICUs) located at various hospitals, the number of Real Donors at each hospital, and the relation between the brain deaths and the number of ICU beds equipped with artificial respirators. The Uruguayan solid organ donation rate is relatively high among Latin American Countries, but low in relation to developed countries. The conversion of potential donors to actual donors is similar to that seen in developed countries. However, the registered incidence of brain deaths in relation to the number of ICU beds is surprisingly below the recognized standard figure. To approach the reasons for this difference, efficient quality control mechanisms are needed in the various ICUs as well as comprehensive medical case history reviews of all patient records.

Brain Death↗

The effects of intrusive loading on axial movements of impeded and unimpeded rat incisors: estimation of eruptive force.

Axial movements of impeded and unimpeded rat mandibular incisors were measured following application and removal of intrusive loads of 1, 2, 5, 10 and 20 mN in a stepwise order at intervals of 1h on erupting teeth. The tooth movements were recorded by a displacement detector under artificial respiration with halothane anaesthesia. The loading and unloading procedures brought about the tooth movements in two steps: an initial rapid movement immediately after application or removal of the load and a subsequent slow and gradual movement. The initial rapid intrusive or extrusive tooth movements were significantly greater in the unimpeded than in the impeded teeth at the same load. The forces to stop extrusive tooth movements, estimated from the formula of regression lines showing correlations between the intrusive loads from 0 to 5 mN and tooth movements (microm/30 min), were 4.2 mN in the impeded and 2.9 mN in the unimpeded incisors. We suggest that repeated shortenings of the rat incisor did not cause an increase in the eruptive force and that changes in the resistance of the periodontal ligament predominantly regulate the axial movement of the rat incisor.

Animals↗

Corticosteroids in the treatment of blunt injury of the chest.

In a prospective, controlled study, the effects of large doses of methylprednisolone sodium succinate (MP) were examined in patients subjected to severe blunt injury of the chest. Forty patients with multiple fractures of ribs were selected for the study. The majority of the patients had associated extrathoracic injuries. Chest X-ray films revealed changes characteristic of pulmonary contusion in all cases. Twenty patients were given MP 30 mg/kg body weight intravenously and were compared with 20 patients receiving no steroids, but who were otherwise treated identically. There were no differences between the two groups with respect to the A-VO2 difference and intrapulmonary shunting. However, the steroid treatment led to a significant reduction in pulmonary vascular resistance and to a reduction of the work of the right side of the heart. The number of complications and periods of artificial respiration were reduced in the steroid group. All patients survived.

Adult↗