Effects of vasodilators on fibrin-induced pulmonary edema,so-called neurogenic pulmonary edema,in the rat

The present study was undertaken to evaluate the effects of vasodilators on the development of neurogenic pulmonary edema. Pulmonary edema was induced by injecting fibrinogen and thrombin into the cisterna magna of vagotomized rats (fibrin-induced pulmonary edema). Before the intrathecal injections, rats were pretreated with intravenous injection of one of the following vasodilators: phentolamine, isoproterenol, nifedipine, diltiazem, isosorbide dinitrate, or substance P. Each vasodilator reduced the incidence of fibrin-induced pulmonary edema and lung-water ratio dose-dependently except nifedipine and diltiazem. There was a uniform relationship between the lung-water ratio and the prefibrin mean arterial pressure obtained under administration of different doses of the each drug. A similar relationship was obtained even if the drug used was different. Treatment with nifedipine or diltiazem, however, diminished the blood pressure but provided less protection against the development of pulmonary edema. The blood volume in edema-positive lungs was minimally different from that in edema-negative lungs. These results suggest that the neurogenic pulmonary edema may be effectively prevented by most vasodilators except Ca⁺⁺-blockers.     

Intrathecal mepivacaine and prilocaine are less neurotoxic than lidocaine in a rat intrathecal model

BACKGROUND AND OBJECTIVES: Histologic evidence of the comparative neurotoxicity of lidocaine, mepivacaine, and prilocaine is incomplete. We compared the intrathecal neurotoxicity in rats among these 3 drugs based on morphologic and neurofunctional findings. METHODS: Rats (n=169) randomly received 0.12 microL/g of 0%, 2%, 5%, 7.5%, 10%, or 20% lidocaine, mepivacaine, or prilocaine or 25% glucose dissolved in distilled water via a chronically implanted intrathecal catheter. The effect of the agents on neurofunction was evaluated by movement of the hind limb (behavior test) and by sensory threshold (paw-stimulation test). The L1 spinal cord, the posterior and anterior roots, and the cauda equina were removed en bloc 5 days later and examined by light and electron microscopy. RESULTS: A significant decrease in sensory threshold or irreversible hind-limb limitation was observed only in rats receiving 20% lidocaine. Morphologic abnormalities characterized by axonal degeneration were observed in rats receiving > or =7.5% lidocaine, 20% mepivacaine, and 20% prilocaine, at the posterior white matter and the proximal portion of the posterior root just at the entrance into the spinal cord. The incidence of lesions was significantly higher in rats receiving lidocaine than mepivacaine and prilocaine. CONCLUSION: It is suggested that intrathecal mepivacaine and prilocaine are less neurotoxic than highly concentrated lidocaine in a rat intrathecal model.     

异氟烷对大鼠急性脊髓损伤后神经源性肺水肿的影响

[目的]探讨吸入异氟烷的大鼠急性脊髓损伤过程中血流动力学变化及损伤后肺组织的病理改变.[方法]成年雄性SD大鼠60只,体重280～330 g,随机分为水合氯醛组、1.5%异氟烷组和3%异氟烷组.在T8水平球囊扩张造成脊髓压迫,术中监测大鼠的血压、心率,压迫结束10 min后处死大鼠,取肺组织称湿、干重,计算湿干重之比;通过大体解剖和光学显微镜观察肺组织的病理变化.[结果]所有进行脊髓压迫的大鼠血压均高于术前基础值(P<0.05),心率均低于术前基础值(P<0.05),1.5%异氟烷组在脊髓压迫过程中的血压上升明显高于水合氯醛组和3%异氟烷组(P<0.05),心率较基础值下降则大于水合氯醛组和3%异氟烷组(P<0.05),水合氯醛组与3%异氟烷组的血压、心率变化差异不显著(P>0.05);1.5%异氟烷组大鼠肺水肿程度较重,肺的湿干重之比较水合氯醛组、3%异氟烷组高,有显著差异(P<0.05),水合氯醛组与3%异氟烷组差异不显著(P>0.05).[结论]使用1.5%异氟烷麻醉的大鼠急性脊髓损伤后肺水肿的发生速度快、严重程度高,可能与难以抑制交感神经的过度兴奋有关,因此在临床上应尽量避免单纯长时间吸入1.5%异氟烷,以防病人术后肺水肿的发生.     

Effects of hypothermia on intracranial pressure and brain edema formation: studies in a rat acute subdural hematoma model

Acute subdural hematoma (SDH) is the most common mass lesion in severe head injury, and brain ischemia is the leading pathophysiological mechanism in the development of secondary brain damage following SDH. Hypothermia has been employed as an effective neuroprotective procedure in clinical and laboratory studies on cerebral ischemic and contusional injuries. In the present study, we used a rat acute SDH model to assess the effect of hypothermia on the intracranial pressure (ICP) and also on the brain edema formation at 4 h after hematoma induction. Mild (34 degrees C) and moderate (32 degrees C) hypothermia did not significantly affect the ICP or cerebral perfusion pressure, but they were associated with a significant lower cortical brain edema formation beneath the hematoma (81.09 +/- 0.49%, p<0.05; and 80.88 +/- 0.17%, p<0.01) when compared with the normothermic control group (81.65 +/- 0.52%). This reduction in brain edema formation was comparable to the results of MK-801 treatment (80.95 +/- 0.35%, p<0.01). The present findings indicate that hypothermia represents a potent neuroprotective strategy. The possible protective mechanisms of hypothermic protection afforded in this rat acute SDH model are discussed.     

Clinical evaluation of neurogenic pulmonary edema following acute stage of subarachnoid hemorrhage]

Clinical characteristics and therapeutic problems of neurogenic pulmonary edema (NPE) occurring in the acute stage of severe subarachnoid hemorrhage (SAH) were examined. The relationship between SAH and NPE was studied in 208 patients who arrived at the hospital in the acute stage (within 24 hours after the onset) of severe SAH in the past nine years. NPE was observed in four (6%) of 64 Grade III patients, nine (18%) of 49 Grade IV patients and 20 (21%) of 95 Grade V patients. Higher grade patients tended to be complicated by NPE more frequently. CT findings of these 33 patients with NPE belonged to Fisher's Group 3 or 4 (23 of 110 group-3 patients and 10 of 88 group-4 patients). Concerning ECG abnormalities, depression of ST segment, abnormal T waves, sinus tachycardia, and right bundle-branch block were observed more frequently in the NPE group than in the non-NPE group. In comparison of the age, blood pressure, PaO2, serum electrolyte, WBC, and blood sugar level on admission between the two groups, significantly higher values of diastolic pressure and blood sugar levels were shown in the NPE group than non-NPE group. The mean interval between the onset of SAH and the diagnosis of NPE on chest film was 2.5 hours, while the NPE findings disappeared within three days after the onset of SAH (mean 1.2 days). In all cases, the NPE findings disappeared after a variety of respiratory managements had been carried out.(ABSTRACT TRUNCATED AT 250 WORDS)     

Opposing effects of isoflurane and sevoflurane on neurogenic pulmonary edema development in an animal model

BACKGROUND: The current study was undertaken to investigate the effects of pretreatment with isoflurane and sevoflurane on the development of neurogenic pulmonary edema in an animal model. METHODS: Rats were exposed to room air (control), 1.5% isoflurane, or 2.5% sevoflurane for 4 h. They were then anesthetized with intraperitoneal injections of pentobarbital sodium, and fibrinogen and thrombin were injected into the cisterna magna to induce neurogenic pulmonary edema. RESULTS: Consecutive injections of fibrinogen and thrombin caused increases in blood pressure, with the peak values obtained in the isoflurane and sevoflurane groups being lower than the control values. The incidence of significant neurogenic pulmonary edema was 58%, 100%, and 8% in the control, isoflurane, and sevoflurane groups, respectively. The lung water ratio, an index of severity of edema, was 4.86 +/- 0.78, 6.15 +/- 0.64, and 4.40 +/- 0.32 in the control, isoflurane, and sevoflurane groups, respectively. Furthermore, immunohistochemical staining for vascular endothelial growth factor demonstrated an increase of expression in the rat lungs exposed to isoflurane. Treatment with an anti-vascular endothelial growth factor antibody during exposure to isoflurane completely inhibited the effect of isoflurane to promote neurogenic pulmonary edema in this model. CONCLUSION: Exposure to 1.5% isoflurane enhances the development of neurogenic pulmonary edema development in this animal model, most likely via release of vascular endothelial growth factor from bronchial epithelial cells, an effect not observed with sevoflurane.     

Radiographical investigations of organic lesions of the hypothalamus in patients suffering from neurogenic pulmonary edema due to serious intracranial diseases: relationship between radiographical findings and outcome of patients suffering from neurogenic pulmonary edema

Radiographical investigations of the hypothalamus by computerized tomography (CT) have rarely been performed despite the fact that the damage to the hypothalamus owing to serious intracranial organic diseases may cause neurogenic pulmonary edema (NPE). We presented 22 consecutive cases of patients suffering from NPE caused by serious intracranial organic diseases and investigated the relationship between NPE and abnormal radiographical findings of the hypothalamus. In 11 cases, organic lesions were noted in the hypothalami and 10 of these patients died of NPE (91.0%). In contrast, of the remaining 11 cases without significant radiographical findings of organic lesions in the hypothalami, only 2 patients were lost (18.2%). In general, various factors including systemic ones are considered to contribute to the prognosis of the patients suffering NPEs caused by serious intracranial diseases. It was concluded that hypothalamic damage was not always found by radiograph in patients with NPE due to critical intracranial diseases, but once abnormal findings in their hypothalamus of these patients were noted, their prognosis would become significantly poor (p < 0.05).     

西地那非对肺动脉高压大鼠肺血管重塑的影响

目的观察磷酸二酯酶V抑制剂西地那非对肺动脉高压大鼠肺血管重塑的影响及其机制。方法40只SD大鼠,体重220～230 g,随机分为4组(n=10)：对照组(C组)、肺动脉高压组(P组)、盐酸西地那非25 mg·kg~(-1)(S1组)、盐酸西地那非50 mg·kg~(-1)组(S2组)。P组、S1组、S2组腹腔注射野百合碱60 mg·kg~(-1)(用生理盐水稀释至1ml),C组给予等量生理盐水。S1组、S2组注射野百合碱后2周腹腔注射相应剂量的盐酸西地那非,每天1次,给药时间持续6周。测定平均动脉压(MAP)及平均肺动脉压(MPAP)后处死大鼠,计算右心室壁重量与左心室+室间隔之和的比值(右心室肥厚指数),光镜下观察肺组织的形态学,计算肺小动脉管壁与管腔厚度的比值(管壁/管腔比),用RT-PCR方法测定肺组织血管内皮生长因子(VEGF)mRNA表达,用Western blot方法测定肺组织总ERK_1/ERK_2、磷酸化ERK_1/ERK_2及MKPl水平。结果野百合碱可导致MPAP、右心室肥厚指数及肺小动脉管壁/管腔比增加,并可增加肺组织VEGF mRNA、磷酸化ERK_1/ERK_2、MKP1水平,但是对MAP无影响,西地那非除增加肺组织MKP1水平外,可减弱野百合碱诱发的上述改变。结论西地那非可减轻肺动脉高压大鼠的肺血管重塑,其机制与下调肺组织VEGF、ERK_1/ERK_2磷酸化水平有关。     

Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension

Background

A pulmonary hypertensive crisis (PHC) can be a life-threatening condition. We established a PHC model by exposing rats with monocrotaline (MCT)-induced pulmonary hypertension to acute hypoxia, and investigated the effects of vasopressin, phenylephrine, and norepinephrine on the PHC.

Ventriculoperitoneal shunt dysfunction in a patient presenting with neurogenic pulmonary edema. Case report

The authors report on a patient with dysfunction of a ventriculoperitoneal shunt who presented with two episodes of neurogenic pulmonary edema within the space of a few months. The edema resolved on correction of the shunt dysfunction. Because neurogenic pulmonary edema may be a rare consequence of shunt dysfunction, it is important to recognize this unusual association and provide appropriate diagnostic measures and treatment.     

Intrathecal anesthesia for cesarean delivery via a subarachnoid drain in a woman with benign intracranial hypertension

A 26-year-old primiparous patient with intractable benign intracranial hypertension treated by cerebrospinal fluid drainage through an indwelling spinal catheter was expecting twins. At 30 weeks she presented for emergent cesarean delivery secondary to a non-reassuring fetal condition. In consultation with the neurosurgical team, spinal anesthesia for the cesarean delivery was induced successfully through the spinal catheter. Cesarean delivery proceeded uneventfully with a favorable neonatal outcome.     

Resolution of pulmonary edema with variable mechanical ventilation in a porcine model of acute lung injury

Objective

Resolution of the acute respiratory distress syndrome (ARDS) requires clearance of pulmonary edema. Biologically variable ventilation (BVV) strategies that improve gas exchange, lung mechanics, and inflammatory mediators in ARDS may be beneficial in this regard. We used quantitative computed tomography (CT), a single indicator thermodilution system (PiCCO?) to determine extravascular lung water (EVLW), and the change in edema protein concentration over time to compare edema clearance with BVV vs conventional mechanical ventilation (CMV) in a porcine ARDS model.

Methods

Sixteen pigs with oleic acid lung injury were randomized to four hours of ventilation with either CMV (n?=?8) or BVV (n?=?8) at identical low tidal volume and minute ventilation over time. Hemodynamic variables, gas exchange, lung mechanics, and PiCCO derived EVLW were determined hourly. Computed tomography images and edema fluid samples were obtained at baseline lung injury and after four hours of ventilation. Wet and dry lung weights were determined postmortem.

Results

At four hours with BVV, peak airway pressure was decreased significantly and lung compliance improved compared with CMV (P?=?0.003; P?P?=?0.001) and a decrease in total lung weight and global lung density (P?=?0.005; P?=?0.04 respectively) with BVV. These findings were associated with a significant increase in the gas volume of normally aerated lung regions (P?P?=?0.001). No change in any CT parameter occurred with CMV. The lung weights derived from computed tomography correlated well with postmortem wet weights (R²?=?0.79; P??1 (3%)) with BVV and negative with CMV (?2.0%??hr^?1 (4%)).

Conclusions

In a comparison between BVV and CMV, computed tomography evidence suggests that BVV facilitates enhanced clearance and/or redistribution of edema fluid with improved recruitment of atelectatic and poorly aerated lung regions; no such evidence was seen with either single thermodilution measurement of EVLW or edema clearance rates. The results of computed tomography provide further evidence of the benefit of BVV over conventional ventilation in ARDS.     

Graft damage after a single lung transplantation for pulmonary hypertension in a rat model

The hemodynamic effect and degree of damage in grafts of single lung transplants for pulmonary hypertension were studied in rats with monocrotaline-induced pulmonary hypertension. Inbred male Lewis rats (weight 200–230 g) were divided into two groups. Group 1 (control group,n = 16) underwent isogenic left lung transplantation, while group 2 (n = 15) received an intravenous administration of monocrotaline (80 mg/kg i.v.) and underwent isogenic left single lung transplantation 3 weeks later. Hemodynamic evaluations were performed prior to transplantation, at 1h postoperatively, and on days 3 and 7 after transplantation. Mean pulmonary arterial pressure (mPAP) rapidly declined after transplantation in group 2, from 39.3 ± 8.7 mmHg to 18.5 ±3.0 mmHg 1h after transplantation, and remained stable on day 7 after tranaplantation. No significant difference in the mPAP between the two groups was observed after tranaplantation. The extravascular lung water volume (ELWV: dry/wet ratio) in the right lung of group 2 significantly increased on day 3 (0.86 ± 0.02) (P < 0.01), and subsequently decreased to control levels on day 7 (0.83 ± 0.02). There was no significant difference in the ELWV in the grafted lungs between the two groups (0.84 ± 0.03 vs 0.86 ± 0.04), but there was tendency toward an increase in ELWV in group 2 on days 3 and 7. These data thus demonstrated that a hemodynamic improvement was obtained by single lung transplantation; however the degree of graft damage was remarkable in the pulmonary hypertension group.     

磷酸二酯酶抑制剂在肺水肿、肺高压和急性肺损伤方面的研究新进展

背景磷酸二酯酶抑制剂（phosphodiesterase inhibitors,PDEIs）是一类抑制磷酸二酯酶（phosphodiesterases,PDEs）活性的药物,其主要作用是抑制PDEs的活性,降低细胞内第二信使环磷酸腺苷（cyclic adenosine monophosphate,cAMP）或环磷酸鸟苷（cyclic guanosine monophosphate,cGMP）的水解,因而提升cAMP或cGMP的浓度,产生多种生物学效应。选择性PDE3、PDE4、PDE5抑制剂早期多应用于心血管功能调整方面,近来扩展到其他治疗领域。目的介绍PDE3、PDE4和PDE5抑制剂在肺水肿、肺高压和急性肺损伤方面的研究新进展。内容肺血管内皮细胞和肺血管平滑肌细胞分别有PDE3、PDE4和PDE5分布,它们在维持血管内皮的完整性以及血管平滑肌的舒缩方面发挥着一定生物学作用。现对PDEIs通过抑制PDE活性,影响肺血管内皮细胞完整性以及肺微血管的舒缩功能,达到保护和维持肺内皮和肺血管功能的作用机制及研究新进展方面进行介绍。趋向通过了解PDEIs药物治疗的药理学基础,有望今后在临床治疗肺高压、肺水肿和肺损伤方面发挥更大的作用。     

Intrathecal chemotherapy with ACNU in a meningeal gliomatosis rat model.

Intrathecal administration of ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso urea hydrochloride) had a remarkable chemotherapeutic effect in a rat model of meningeal gliomatosis. This effect was evaluated in rats with meningeal gliomatosis induced by an intracisternal inoculation of rat C6 glioma cells. The median survival time of the rats treated with a single dose of intrathecal ACNU (1 mg/kg) on Day 1 or Day 3 after tumor inoculation was significantly prolonged by 35.7% to 42.9% or 25.0% to 28.6%, respectively, as compared with that of the control animals. Meningeal gliomatosis rat models treated intrathecally with ACNU (1 mg/kg) 5 days after tumor inoculation or intravenously with ACNU (15 mg/kg) both failed to prolong the survival time of the animals. These findings suggest that intrathecal chemotherapy with a low dose of ACNU is effective in the early stages of meningeal gliomatosis, whereas intravenous chemotherapy with a high dose of ACNU is always ineffective.