Uso compasional de tigeciclina intraventricular en pacientes con ventriculitis causada por Enterococcus faecium. Reporte de seis casos pediátricos / Compassional use of Intraventricular Tigecycline in ventriculitis caused by Enterococcus faecium. Six pediatric cases

Introducción: La Tigeciclina es un fármaco de uso restringido en pediatría. El uso de este antibiótico por vía intraventricular es una decisión de uso compasivo en casos de bacterias altamente resistentes, y para los casos en que no exista otra alternativa. Caso clínico: Se presenta seis casos de pacientes con diagnóstico de ventriculitis a Enterococcus faecium que recibieron tigeciclina intraventricular con evolución bacteriológica exitosa. Se discute las dosis utilizadas por vía endovenosa e intraventricular. Conclusiones: el uso de este antibiótico por vía intraventricular puede ser una alternativa exitosa en casos de gérmenes altamente resistentes y cuando no exista otra alternativa terapéutica.

Introduction: Tigecycline is a drug of restricted use in pediatrics. The use of this antibiotic intraventricularly is a decision of compassive use in cases of highly resistant bacteria, and in cases where there is no other alternative. Clinical case: We present six cases of patients with a diagnosis of ventriculitis caused by Enterococcus faecium, who received intraventricular tigecycline with successful microbiological evolution. The doses used intravenously and intraventricularly are discussed. Conclusions: the use of this antibiotic intraventricularly can be a successful alternative in cases of highly resistant germs, when there are not alternative options. Key words: ventriculitis, Enterococcus faecium, tigecycline, intraventricula

Efficacy of Slow Rate Ventriculolumbar Perfusion Chemotherapy for Leptomeningeal Carcinomatosis: Interim Result of a Phase II Study

BACKGROUND: To evaluate the efficacy of modified ventriculolumbar perfusion (VLP) chemotherapy with methotrexate on leptomeningeal carcinomatosis in terms of symptomatic response and side effects. METHODS: Previous infusion rate of 20 mL/h was reduced to 15 mL/h for the purpose of decreasing constitutional side effects of VLP such as nausea/vomiting, insomnia and confusion. The primary outcome was the response rate of increased intracranial pressure (ICP), and the secondary outcome was the occurrence of side effects compared to previous 20 mL/h trial. This interim analysis to validate the reduced infusion rate is not to affect the original effect of VLP chemotherapy. RESULTS: All forty-seven patients were enrolled including 22 patients with increased ICP. Thirteen patients out of these (59%) got normalized ICP after VLP chemotherapy. Moderate to severe (grade 2–3) confusion was observed in 3 patients (6%) and it was significantly reduced compared to those (23%) in the VLP 20 mL/h (p=0.017). Grade 2–3 nausea/vomiting was also reduced from 64% to 45% but failed to reach statistical significance (p=0.08). Median overall survival (OS) was 5.3 months (95% confidence interval, 3.55–7.05) and patients OS, who received maintenance VLP was significantly prolonged compared to patients who underwent induction VLP only (5.8 vs. 3.4 months, p=0.025). CONCLUSION: VLP of reduced perfusion rate (15 mL/h) showed compatible control rate of increased ICP at this interim analysis. Decreased moderate to severe side effects and prolonged OS in patients received maintenance VLP encourage us to evaluate the effectiveness of this trial further.

Chronic Intracerebroventricular Infusion of Metformin Inhibits Salt-Sensitive Hypertension via Attenuation of Oxidative Stress and Neurohormonal Excitation in Rat Paraventricular Nucleus / 神经科学通报·英文版

Metformin (MET), an antidiabetic agent, also has antioxidative effects in metabolic-related hypertension. This study was designed to determine whether MET has anti-hypertensive effects in salt-sensitive hypertensive rats by inhibiting oxidative stress in the hypothalamic paraventricular nucleus (PVN). Salt-sensitive rats received a high-salt (HS) diet to induce hypertension, or a normal-salt (NS) diet as control. At the same time, they received intracerebroventricular (ICV) infusion of MET or vehicle for 6 weeks. We found that HS rats had higher oxidative stress levels and mean arterial pressure (MAP) than NS rats. ICV infusion of MET attenuated MAP and reduced plasma norepinephrine levels in HS rats. It also decreased reactive oxygen species and the expression of subunits of NAD(P)H oxidase, improved the superoxide dismutase activity, reduced components of the renin-angiotensin system, and altered neurotransmitters in the PVN. Our findings suggest that central MET administration lowers MAP in salt-sensitive hypertension via attenuating oxidative stress, inhibiting the renin-angiotensin system, and restoring the balance between excitatory and inhibitory neurotransmitters in the PVN.

A velocidade de infusão da solução poli-iônica intravenosa contendo 84mEq/L de lactato determina a intensidade do efeito alcalinizante em equinos / The intravenous polyionic solution with 84mEq/L of lactate infusion rate determines the intensity of the alkalizing effect in horses

O objetivo deste trabalho foi verificar os efeitos da solução poli-iônica intravenosa contendo 84mEq/L de lactato (L84) sobre os equilíbrios hidroeletrolítico e ácido-base de equinos, quando administrada de forma rápida ou lenta. Cinco equinos sadios adultos receberam a infusão contínua intravenosa da L84, em volume correspondente a 10% do peso corporal, em duas ocasiões: a) infusão rápida (16,66mL/kg/h) durante seis horas; b) infusão lenta (8,33mL/kg/h) durante 12 horas. Amostras de sangue venoso foram colhidas ao início da infusão (hora zero) e três, seis, nove, 12 e 24 horas após, e amostras de urina nas horas zero, seis, 12 e 24. Determinaram-se pH (sanguíneo e urinário), pCO2, HCO3 -, BE, PPT, lactato L, Na+, K+, Cl-, AG, SID, Atot, VVP, densidade urinária e excreções fracionadas urinárias de lactato L, Na+, K+ e Cl-. A L84 provoca efeito alcalinizante iatrogênico de menor magnitude quando administrada de forma lenta, porque os mecanismos renais, atuantes durante o período de infusão, promovem a correção gradativa do desequilíbrio. Pode-se concluir que a infusão de forma lenta da solução L84 em equinos é recomendável nos casos em que se suspeite de acidose metabólica e não seja possível quantificar o grau do desequilíbrio.(AU)

The aim of this study was to investigate the effects of an intravenous polyionic solution containing 84mEq/L of lactate (L84) on the hydroelectrolyte and acid-base balances when administered quickly or slowly in horses. Five healthy adult horses received the L84 solution, in a volume corresponding to 10% of BW, by continuous intravenous infusion, in two instants: a) rapid infusion (16.66mL/kg/h) during 6 hours; b) slow infusion (8.33mL/kg/h) during 12 hours. Venous blood samples were taken at the beginning of the infusion (hour 0) and 3, 6, 9, 12, and 24 hours after. Urine samples were taken at 0, 6, 12, and 24h. pH (blood and urine), pCO2, HCO3-, BE, TPP, L-lactate, Na+, K+, Cl-, AG, SID, Atot, PVV, urine specific gravity, and L-lactate, Na+, K+, and Cl- renal fractional clearance were determined. The L84 solution causes lower magnitude alkalizing effect when administered slowly, due to the gradual correction of the iatrogenic imbalance by the kidneys during the infusion period. The L84 solution infused at a low rate in horses could be recommended in cases where metabolic acidosis is suspected and it is not possible to quantify the imbalance degree.(AU)

Evidence for the involvement of peripheral -adrenoceptors in delayed liquid gastric emptying induced by dipyrone, 4-aminoantipyrine, and antipyrine in rats

Dipyrone (Dp), 4-aminoantipyrine (AA), and antipyrine (At) delay liquid gastric emptying (GE) in rats. We evaluated adrenergic participation in this phenomenon in a study in male Wistar rats (250-300 g) pretreated subcutaneously with guanethidine (GUA), 100 mg·kg−1·day−1, or vehicle (V) for 2 days before experimental treatments. Other groups of animals were pretreated intravenously (iv) 15 min before treatment with V, prazosin (PRA; 1 mg/kg), yohimbine (YOH; 3 mg/kg), or propranolol (PRO; 4 mg/kg), or with intracerebroventricular (icv) administration of 25 µg PRO or V. The groups were treated iv with saline or with 240 µmol/kg Dp, AA, or At. GE was determined 10 min later by measuring the percentage of gastric retention (%GR) of saline labeled with phenol red 10 min after gavage. %GR (mean±SE, n=8) indicated that GUA abolished the effect of Dp (GUA vs V=31.7±1.6 vs 47.1±2.3%) and of At (33.2±2.3 vs 54.7±3.6%) on GE and significantly reduced the effect of AA (48.1±3.2 vs 67.2±3.1%). PRA and YOH did not modify the effect of the drugs. %GR (mean±SE, n=8) indicated that iv, but not icv, PRO abolished the effect of Dp (PRO vs V=29.1±1.7 vs 46.9±2.7%) and At (30.5±1.7 vs 49±3.2%) and significantly reduced the effect of AA (48.4±2.6 vs 59.5±3.1%). These data suggest activation of peripheral β-adrenoceptors in the delayed GE induced by phenylpyrazolone derivatives.

Uroguanylin induces electroencephalographic spikes in rats / Uroguanilina induz potenciais em espiga no eletroencefalograma de ratos

Uroguanylin (UGN) is an endogenous peptide that acts on membrane-bound guanylate cyclase receptors of intestinal and renal cells increasing cGMP production and regulating electrolyte and water epithelial transport. Recent research works demonstrate the expression of this peptide and its receptor in the central nervous system. The current work was undertaken in order to evaluate modifications of electroencephalographic spectra (EEG) in anesthetized Wistar rats, submitted to intracisternal infusion of uroguanylin (0.0125 nmoles/min or 0.04 nmoles/min). The current observations demonstrate that 0.0125 nmoles/min and 0.04 nmoles/min intracisternal infusion of UGN significantly enhances amplitude and frequency of sharp waves and evoked spikes (p = 0.03). No statistical significance was observed on absolute alpha and theta spectra amplitude. The present data suggest that UGN acts on bioelectrogenesis of cortical cells by inducing hypersynchronic firing of neurons. This effect is blocked by nedocromil, suggesting that UGN acts by increasing the activity of chloride channels.

A uroguanilina (UGN) é um peptídeo endógeno que age em receptores do tipo guanilato ciclase de membrana de células intestinais e renais aumentando a produção de GMPc e regulando o transporte epitelial de eletrólitos e água. Pesquisas recentes demonstraram a expressão deste peptídeo e de seus receptores no sistema nervosa central. O presente trabalho foi realizado com objetivo de avaliar possíveis mudanças no espectro do eletroencefalograma (EEG) de ratos Wistar anestesiados, submetidos à infusão intracisternal de uroguanilina (0.0125 nmoles/min or 0.04 nmoles/min). Os resultados apresentados no corrente trabalho demonstram que a infusão intracisternal de ambas as doses de UGN aumenta significativamente a amplitude e frequência das espículas (p = 0.03). Não foram encontradas diferenças estatísticas na amplitude absoluta dos espectros alfa ou teta. Os dados apresentados neste trabalho mostram que a UGN age na bioeletrogênese de células corticais induzindo disparo hipersincrônico de neurônios. Este efeito é bloqueado por nedocromil, sugerindo que UGN atua pelo aumento de atividade de canais de cloreto.

Intracerebroventricular administration of adenosine A1 receptor antisense oligodeoxynucleotide inhibites the neuroprotective effect of the cerebral ischemic preconditioning in rats / 中国应用生理学杂志

<p><b>AIM</b>To further explore the role of adenosine A1 receptor in the neuroprotective effect of cerebral ischemic preconditioning, the present study was undertaken to observe the effect of inhibiting expression of adenosine Al receptor with adenosine A1 receptor antisense oligodeoxynucleotide (ARA1 As-ODN) on the neuroprotective effect of cerebral ischemic preconditioning against delayed neuronal death (DND) normally induced by lethal brain ischemia.</p><p><b>METHOD</b>The rat 4-vessel occlusion global cerebral ischemic model was used. Forty-eight male Wistar rats with permanent occlusion of the bilateral vertebral arteries were divided into 8 groups: Sham, CIP, brain ischemic insult, CIP + brain ischemic insult, Distilled water + CIP + brain ischemic insult, ARA1 As-ODN, ARA1 As-ODN +CIP, ARA1 As-ODN+ CIP + brain ischemic insult(two doses of 10 nmol/5 microl and 20 nmol/5 microl were used) groups. ARA1 As-ODN was dissolved in distilled water and injected into the right lateral cerebral ventricle. To illustrate the profile of DND, histological grade (HG) and neuronal density (ND) in the CA1 region of the hippocampus were examined 7 d after the sham operation or the last time of ischemia under thionin staining.</p><p><b>RESULTS</b>The HG and ND in CIP group were similar to those in sham group. Brain ischemic insult induced obvious DND as represented with the increase in HG and decrease in ND significantly (P < 0.05 vs. sham and CIP groups). In CIP + ischemic insult group,no obvious DND was observed,which indicated that CIP protected pyramidal neurons against the ischemic insult.While the administration of ARA1 As-ODN in ARA1 As-ODN + CIP + brain ischemic insult group caused obvious increase in HG and decrease in ND compared with CIP + brain ischemic insult group (P < 0.05) in a dose dependent manner,which indicated that the neuroprotective effect of CIP against DND of hippocampal pyramidal neurons normally induced by ischemic insult was inhibited by the administration of ARA1 As-ODN.</p><p><b>CONCLUSION</b>The results further demonstrate the association of up-regulation of adenosine A1 receptors with the induction of CIP-mediated BIT.</p>

[ antinociceptive effect of intracerebroventricular injection of soya oil in mice]

Several studies have shown that Soya oil has analgesic effects when it administered orally or injected. Oral administration of Soya oil has antinociceptive effect on bone dysplasia induced pain. Based on previous reports concerning analgesic effect of peripheral administration of Soya oil and the usage of the oil as a solvent or the oil part of emulsions to prepare water insoluble drugs, we investigated the analgesic effect of intracerebroventricular [i.c.v.] injection of Soya oil. The antinociceptive effects of i.c.v. administration of Soya oil using formalin test have been studied in stereotaxed mice after one week of surgery and insertion of a stainless steel canulla in the right cerebroventricle. Administration of pure Soya oil induced an antinociceptive effect in mice but the oil did not show any analgesic effects in 10 percent concentration. The results of this study are in agreement with previous data on analgesic effect of peripheral administration of Soya oil. Therefore, we suggest that minimum concentrations should be used to prepare emulsions with Soya oil for water insoluble drugs in antinociception studies

Prolaction May not Stimulate Generation of New Cells after Transient Focal Cerebral Ischemia in Adult Male Rat Brain: a Preliminary Study

BACKGROUND: Production of neuronal progenitors is usually stimulated in the forebrain subventricular zone of mice after the intracerebroventricular infusion of prolactin. As a preliminary study, we infused prolactin to the male rat brain to test the hypothesis that prolactin promotes new cell proliferation in the brain and functional recovery after focal ischemia. METHODS: Male rats were subjected to intraluminal middle cerebral artery occlusion. Prolactin was administered to the surface of the brain for 5 or 14 days starting 24 or 48 hours after stroke onset at doses of 6.4 microgram per day. We administered the same volume of saline to the other ischemic rats used as a control group. Some rats were killed 6 or 17 days after stroke for analysis of infarct volume and newly generated cells within the subventricular zone and the striatum. The other rats were tested for neurological recovery 24 days after stroke. RESULTS: There was no significant difference of infarct volume among the experiment groups. Treatment with prolactin did not increase the numbers of bromodeoxyuridine-immunoreactive cells in the subventricular zone and the striatum. Treatment with prolactin did not enhance neurological recovery in all tests performed. CONCLUSIONS: In this preliminary study, prolactin did not enhance new cell generation in the male rat brain nor reduce the neurological deficits after ischemic stroke.

Pressor Responses to Intracerebroventricular Infusion of Hypertonic NaCl in Renal Hypertensive Rats

BACKGROUND: The sodium concentration in the central nervous system may play an important role in cardiovascular function and body fluid regulation. The purpose of this investigation was to examine the effects of intracerebroventricular (ICV) infusion of hypertonic NaCl solutions on the cardiovascular responses in normotensive and 2-kidney, 1 clip (2K1C) renal hypertensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and were used 4 weeks later. Age-matched control rats received a sham treatment. Under thiopental (50 mg/kg, IP) anesthesia, both isotonic and hypertonic NaCl solutions (0.15 M, 0.6 M and 1.2 M) were ICV applied, while blood pressure and heart rate (HR) responses were continuously monitored. RESULTS: Central administration of hypertonic NaCl solution caused an elevation in mean arterial pressure (MAP) and HR in both normotensive and 2K1C hypertensive rats. The response magnitude in the blood pressure was positively correlated to the NaCl concentration in normotensive rats, while the pressor responses to hypertonic NaCl were comparable regardless of the concentration of NaCl in hypertensive rats. Despite of the HR responses were similar in between two groups, the magnitude of the MAP increases were more elevated in hypertensive than in normotensive control rats. Isotonic NaCl solution, when centrally applied, caused an elevation in blood pressure only in hypertensive rats. CONCLUSION: These results indicate that the central sensitivity to sodium chloride is altered in 2K1C renal hypertensive rats.

Antibiotic Concentrations of Cerebrospinal fluid in Patients with Various Amount of Extraventricular Drainage during Intraventricular Infusion

Phamacokinetic study of the antibiotic concentrations in the cerebrospinal fluid was done with high pressure liquid chromatography of CSF samples from twelve patients who had various amount of continuous extra-ventricular drainage during antibiotic administration. Five patients with large amount(over 150cc/day) of drainage had decreased CSF antibiotic concentrations dramatically below the effective concentration within 4 hours after intraventricular antibiotic administration, but six patients with small(less than 150cc/day) drainage maintained CSF antibiotic level above effective concentration even 24 hours after administration. In conclusion, repeated intraventricular administration of antibiotic is necessary to maintain the effective drug level in the patient with CSF drainage over 150cc/day.

Clinical Analysis of the Effect of the Continuous External Ventricular Drainage with Urokinase Irrigation for the Treatment of Intraventricular Hemorrhage

The mortality and morbidity of the intraventricular hemorrhage(IVH) has been decreased since the introduction of external ventricular drainage(EVD) and direct intraventricular infusion of urokinase as an effective therapeutic method. In 1989, we already reported a series of 54 cases of IVH treated with simple EVD or EVD with urokinase irrigation in a few cases. Authors analyzed again a series of 50 cases of IVH treated by EVD with direct intraventricular urokinase irrigation after the pervious report. The mortality rate was 55.5% in former occasion, however 18% in this study and the complications were considerably low. We experienced again that the EVD with urokinase irrigation is an effective method and convenient, simple technique in the management of IVH even though there is no ICP monitoring. So we prefer EVD with urokinase irrigation therapy in managing the IVH even if the patient is moribund state.

The Analysis of Intraventricular Hemorrhage Treated with Simple EVD or Infusion of Urokinase

Among all of the spontaneous TCH(intracerebral hemorrhage), the presence of IVH(intraventricular hemorrhage) is showing higher mortality and morbidity. Since the introduction of EVD(extraventricular drainage) and direct intraventricular infusion of Urokinase as a effective therapeutic methods of IVH, it's mortality and morbidity has been decreased. But, in cases of hemorrhage extended into all ventricular chambers showes poor prognosis even the EVD and infusion of Urokinase. Authors analyzed 40 cases of IVH treated with simple EVD or direct intraven-tricular infusion of Urokinase. The results were as follows: 1) The most common age groups of IVH patients were 5th and 6th decades and 22 patients were male, 18 patients were female. 2) All 15 cases of Urokinase treated group revealted over the 7 point of Graeb score. 3) On admission, Glasgow coma scale scores were under the 8 at the 11 cases(73%) of Urokinase treated group and 18 cases(72%) of simple EVD group. 4) Time of cleared ventricles showed fast at the Urokinase treated group than simple EVD group. 5) Incidence of complications were similar on both groups. 6) Prognosis revealed lower morbidity and mortality at the Urokinase treated group than simple EVD group. 7) In cases of high Graeb score and low Glasgow coma scale on admission showed poor prognosis in both groups.

Sudies About the Pressor Response to Intracerebroventricular Infusion of Hypertonic NaCl in Rabbits

Changes of blood pressure, heart rate, ECG, respiration rate and pupil size by intracerebroventricular(ICV) infusion of hypertonic NaCl with 0.04 ml/min for 5 min(total 0.2ml) were observed in urethane-anesthetized rabbits. ICV infusion of 0.75M NaCl produced slight pressor effect (11mmHg) and did not affect other parameters. ICV infusion of 1.5M NaCl began to increase blood pressure from 2~3 min after the infusion and produced maximal increase(24mmHg) at 5~10 min. Then the pressor effect was recovered to the original level at 30~60 min. Change of heart rate by the infusion was not clear, but ST-segment of ECG was markedly depressed. Respiration rate increased about 1.5 times than the control in accordance with the pressor effect and the state was continued even after the recover of the pressor effect. Both pupils dilated markedly and light-reflex was lost. Changes of parameters by ICV infusion of 3.0M NaCl were similar to those by 1.5M NaCl and some rabbits caused severe arrhythmias and died. The purpose of present study is to investigate the mechansim(s) of the pressor effect induced by the ICV infusion of 1.5M NaCl. The pressor effect of 1.5M NaCl was attenuated by the continuous infusion of vasopressin antagonist(20microm/kg/min) but not affected by intravenous treatment with 2mg/kg phentolamine, 2mg/kg propranolol and 1mg/kg chlorisondamine. The pressor effect was not altered with ICV 0.12mg/kg phenoxybenzamine, 0.4mg diltiazem, 0.1mg/kg mecamylamine and 0.2mg/kg atropine. After ICV infusion of 25microg/kg/min of diazepam, however, the pressor effect was completely abolished and restored 3~4 hours after stopping diazepam infusion. The pressor effect was rather potentiated than inhibited in bilateral adrenalectomized or nephrectomized rabbits. Infusion of 2microg/kg/min of saralasin for 10 min in the bliateral adrenalectomized rabbit did not affect the pressor effect at all. These results suggest that hypertensive effect induced by ICV infusion of hypertonic NaCl is mediated by the increase of vasopressin secretion.

Effect of Phentolamine on the Lung and Hypothalamic Lesions in the Experimental Neurogenic Ulmonary Edema in Cats

This experiment was performed to define the paricipation of a discrete hypothalamic neural structure in the genesis of pulmonary edema and the effect of alpha adrenergic blockade. Fifty adult cats weighing 2.5 to 4.0 Kg, were used in this study. The components of the pathophysiological systemic changes, lung weight, and histopathological changes of lung and hypothalamus were studied in groups of animals when intracranial pressure(ICP) was raised to 200 mmH2O of 300 mmH2O for 2 hours by intraventricular infusion with normal saline. The animals were divided into 5 groups : The normal control group was comprised in 10 normal cats. Control and phentolamine treated animal groups which had an elevated ICP of up 200 mmH2O consisted of 10 cats each. Control and phentolamine treated animal groups which had an elevated ICP of up to 300 mmH2O consisted of 10 cats each. The results obtained were as follows : 1) In the animal groups of elevated ICP to 200 mmH2O or 300 mmH2O, there were hemodynamic systemic changes which were neurogenically mediated and caused an immediate elevation in blood pressure of 30 mmHg to 60 mmHg. The hemodynamic data of the animals that had an elevated ICP of up to 300 mmH2O were significantly more deviated from normal control values than the 200 mmH2O ICP groups. The hemodynamic responses of the phentolamine treated animal with elevated ICP of up to 200 and 300 mmH2O were less deviated from normal control values. 2) The lung weights of the animals with an elevated ICP of up to 200 and 300 mmH2O were significantly heavier than the normal control value(p<0.05) and the lung weights of the animals with an elevated ICP of 300 mmH2O were significantly heavier than those with an ICP of 200 mmH2O(p<0.01). The lung weights of the phentolamine treated animal groups were significantly lighter than the control group but showed little increase in the lung weight when compared to the normal value. 3) By controlling the elevated ICP above 200 mmH2O in the experimental animals we have confirmed gross and microscopic appearances of hemorrhagic pulmonary edema. Histopathological changes of the phentolamine treated animals were significantly less sever than in the control groups. 4) By elevating ICP above 200 mmH2O in the experimental animals, we have confirmed discrete bilateral hemorrhagic spots of the anterior hypothalamus, preoptic region induced by increased intracranial pressure. Histopathological changes of the phentolamine treated animals with the elevated ICP were significantly less severe than of the control groups. 5) This experimental model may define the specific particification of the hypothalamus in the pathophysiological pathogenesis of neurogenic pulmonary edema. These results suggest that the lungs are directly affected by the intense sympathetic discharge evoked by release phenomenon from the sympathoinhibitory influence of the hypothalamus, and pulmonary edema was effectively eliminated by alpha adrenergic blockade.

Effect of the Alpha-Adrenergic Blockade in Experimental Neurogenic Pulmonary Edema in Cats

An experimental neurogenic pulmonary edema model in cats is described in which we have attempted to produce a neurogenically mediated hemodynamic storm. This experimental study was done to better define the hemodynamic responses to the elevated intracranial pressure and the effect and role of the alpha-adrenergic blockade in the neurogenic pulmonary edema. 50 adult cats weighing 2.5 to 4.0kg, were used in this study. The components of the pathophysiological hemodynamic responses, systemic changes, lung weight, and histopathological changes of lung in experimental models were studied in groups of animals when intracranial pressure(ICP) was raised for 2 hours by intraventricular infusion with normal saline to 200mmH2O and 300mmH2O. We have also observed the effect of the alpha-adrenergic blockade(pentolamin) in the neurogenic pulmonary edema which was produced by elevated intracranial pressure. The animals were divided into 5 groups: The normal control group was comprised of 10 normal cats. Control and pentolamin treated animal groups which had an elevated ICP of up to 200mmH2O consisted of 10 cats each. Control and pentolamin, treated animal groups which had an elevated ICP of up to 300mmH2O consisted of 10 cats each but in addition they had a neurogenically mediated pulmonary edema. 1) In the animal groups of elevated ICP to 200mmH2O and 300mmH2O, there were hemodynamic systemic changes which were neurogenically mediated and resulted in an immediate elevation in blood pressure from 30mmHg to 60mmHg. There was also bradycardia, a slight elevation of central venous pressure, and reduction of PaO2 during the controlling of the elevated ICP. The hemodynamic responses of the animals that had an elevated ICP of up to 300mmH2O were significantly more changed than the 20mmHO ICP group. The hemodynamic responses of the pentolamin treated animals with elevated ICP to up to 200 and 300mmH2O were less changed and nearly approached the normal limit. 2) This animal model allows quantitative measurement of the neurogenically mediated pulmonary edema of the lungs by weighing. The lung weights of the animals with an elevated ICP of up to 200 and 300mmH2O were significantly greater then the normal control value(P<0.05) and the lung weights of the animals with an elevated ICP of 300mmH2O were significantly greater than those with an ICP of 200mmH2O(P<0.01). The lung weights of the pentolamin treated animal groups with the elevated ICP were significantly less than the control group but showed little increase in the lung weight when compared to the normal value. 3) By controlling the elevated ICP above 200mmH2O in the experimental animals we have confirmed gross and micropic appearances of hemorrhagic pulmonary edema. Partial destruction and congestion appeared along with hemorrhage in the alveolar and alveolar wall in the groups with an ICP of 300mmH2O. Histopathological changes of the pentolamin treated animals with the elevated ICP were significantly less severe than in the control groups and also had a tendency of returning to to a normal state. 4) This experimental model may facilitate clarification of the pathophysiolagical pathogenesis of neurogenic pulmonary edema. The authors defined the concept of neurogenic pulmonary edema as resulting from an increase in pulmonary capillary permeability mediated by massive symphathetic discharges to those vessels. Blockade of the sympathetic innervation to the systemic and pulmonary vascular beds lower the vascular pressures and brings the pulmonary capillary pressures back to normal.