Effect of chronic ethanol exposure on rat ventilatory responses to hypoxia and hypercapnia

OBJECTIVE: The effect of chronic ethanol exposure on chemoreflexes has not been extensively studied in experimental animals. Therefore, this study tested the hypothesis that known ethanol-induced autonomic, neuroendocrine and cardiovascular changes coincide with increased chemoreflex sensitivity, as indicated by increased ventilatory responses to hypoxia and hypercapnia. METHODS: Male Wistar rats were subjected to increasing ethanol concentrations in their drinking water (first week: 5% v/v, second week: 10% v/v, third and fourth weeks: 20% v/v). At the end of each week of ethanol exposure, ventilatory parameters were measured under basal conditions and in response to hypoxia (evaluation of peripheral chemoreflex sensitivity) and hypercapnia (evaluation of central chemoreflex sensitivity). RESULTS: Decreased respiratory frequency was observed in rats exposed to ethanol from the first until the fourth week, whereas minute ventilation remained unchanged. Moreover, we observed an increased tidal volume in the second through the fourth week of exposure. The minute ventilation responses to hypoxia were attenuated in the first through the third week but remained unchanged during the last week. The respiratory frequency responses to hypoxia in ethanol-exposed rats were attenuated in the second through the third week but remained unchanged in the first and fourth weeks. There was no significant change in tidal volume responses to hypoxia. With regard to hypercapnic responses, no significant changes in ventilatory parameters were observed. CONCLUSIONS: Our data are consistent with the notion that chronic ethanol exposure does not increase peripheral or central chemoreflex sensitivity. .

Patient-controlled epidural analgesia with fentanyl and bupivacaine provides better analgesia than intravenous morphine patient-controlled analgesia for early thoracotomy pain.

BACKGROUND: Intravenous patient-controlled analgesia (IVPCA) and patient-controlled epidural analgesia (PCEA) were studied in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery for 24h. PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and is associated with fewer side effects. AIMS: To compare IVPCA and PCEA in terms of analgesic efficacy, respiratory function and side effects after thoracic surgery. SETTINGS AND DESIGN: Tertiary care teaching hospital. Prospective, randomized and open study. MATERIALS AND METHODS: Thirty ASA-I or II patients undergoing thoracotomy were assigned randomly to receive either IVPCA using morphine or PCEA using fentanyl and bupivacaine combination postoperatively. No background infusion was administered in either group. Postoperative evaluation included pain intensity both at rest and during coughing, degree of sedation, arterial blood gas, forced vital capacity (FVC), peak expiratory flow rate (PEFR), presence of side effects such as nausea/vomiting and pruritus at 0, 2, 8, 12 and 24h. The primary outcome of the study was the percentage of patients with analgesia failure defined as VAS>30 despite three consecutive PCA boluses requiring rescue analgesia with intravenous fentanyl. STATISTICAL ANALYSIS: Data were analyzed using t -test, chi2 test and Mann-Whitney test. RESULTS: Significantly less number of patients required rescue analgesia in PCEA group ( P< 0.05). Pain relief was better both at rest and during coughing ( P< 0.05) in PCEA group as compared to IVPCA. Patients in the PCEA group were less sedated and had fewer incidences of side effects, i.e. nausea/vomiting and pruritus. Postoperative FVC and PEFR were reduced significantly compared to baseline only in IVPCA group ( P< 0.05). CONCLUSION: After thoracic surgery, PCEA using fentanyl and bupivacaine as compared to IVPCA using morphine provides better pain relief both at rest and during coughing and associated with fewer side effects.

Thoracic sympathetic block reduces respiratory system compliance

CONTEXT AND OBJECTIVE: Thoracic epidural anesthesia (TEA) following thoracic surgery presents known analgesic and respiratory benefits. However, intraoperative thoracic sympathetic block may trigger airway hyperreactivity. This study weighed up these beneficial and undesirable effects on intraoperative respiratory mechanics. DESIGN AND SETTING: Randomized, double-blind clinical study at a tertiary public hospital. METHODS: Nineteen patients scheduled for partial lung resection were distributed using a random number table into groups receiving active TEA (15 ml 0.5 percent bupivacaine, n = 9) or placebo (15 ml 0.9 percent saline, n = 10) solutions that also contained 1:200,000 epinephrine and 2 mg morphine. Under general anesthesia, flows and airway and esophageal pressures were recorded. Pressure-volume curves, lower inflection points (LIP), resistance and compliance at 10 ml/kg tidal volume were established for respiratory system, chest wall and lungs. StudentÆs t test was performed, including confidence intervals (CI). RESULTS: Bupivacaine rose 5 ± 1 dermatomes upwards and 6 ± 1 downwards. LIP was higher in the bupivacaine group (6.2 ± 2.3 versus 3.6 ± 0.6 cmH2O, p = 0.016, CI = -3.4 to -1.8). Respiratory system and lung compliance were higher in the placebo group (respectively 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0.003, CI = 19.1 to 23.7; 127.2 ± 31.7 versus 70.2 ± 23.1 ml/cmH2O, p < 0.001, CI = 61 to 53). Resistance and chest wall compliance showed no difference. CONCLUSION: TEA decreased respiratory system compliance by reducing its lung component. Resistance was unaffected. Under TEA, positive end-expiratory pressure and recruitment maneuvers are advisable.

CONTEXTO E OBJETIVO: Os benefícios pós-operatórios da anestesia peridural torácica (APT) na analgesia e respiração após toracotomias são conhecidos. Contudo, bloqueio simpático torácico pode desencadear hiperreatividade das vias aéreas. Este estudo pesou tais efeitos benéficos e indesejáveis na mecânica respiratória intra-operatória. TIPO DE ESTUDO E LOCAL: Estudo clínico, randomizado, duplo-cego realizado em hospital público terciário. MÉTODOS: Uma tabela de números aleatórios dividiu 19 pacientes submetidos a ressecção pulmonar parcial entre duas soluções administradas na APT: ativa (15 ml 0,5 por cento bupivacaína, n = 9) ou placebo (15 ml 0,9 por cento NaCl, n = 10). Ambas continham epinefrina 1:200,000 e morfina 2 mg. Sob anestesia geral, pressões esofágicas e de vias aéreas foram registradas. Curvas de pressão versus volume, pontos de inflexão inferior (PII), resistências e complacências sob volume corrente de 10 ml.kg-1 foram aferidos para sistema respiratório, parede torácica e pulmões. O teste t de Student foi realizado (p < 0,005), incluindo intervalos de confiança (IC). RESULTADOS: A dispersão cefálica e caudal da bupivacaína foi, respectivamente, de 5 ± 1 e de 6 ± 1 dermátomos. A curva PII foi maior no Grupo Bupivacaína (6,2 ± 2,3 versus 3,6 ± 0,6 cm H2O, p = 0,016, IC = -3,4 a -1,8). Complacências do sistema respiratório e pulmões foram maiores no Grupo Placebo (respectivamente 73.3 ± 10.6 versus 51.9 ± 15.5, p = 0,003, IC = 19,1 a 23,7, e 127,2 ± 31,7 versus 70,2 ± 23,1 ml.cm H2O-1, p < 0,001, IC = 61 a 53). Resistências e complacências da parede torácica não mostraram diferenças. CONCLUSÃO: APT diminui a complacência do sistema respiratório por reduzir seu componente pulmonar. Resistências não são afetadas. Sob APT, pressão positiva expiratória final e manobras de recrutamento são recomendáveis.

The Reflex Effects on the Respiratory Regulation of the CO2 at the Different Flow Rate and Concentration

PURPOSE: The purpose of this study was to investigate the activation of the respiratory centers during insufflation of the larynx with CO2 at different flow rates and concentrations. MATERIALS AND METHODS: The experiments were carried out in spontaneous air breathing rabbits, anesthetized with thiopental sodium (25mg kg(-1) i.v.). The larynx was separated from the oropharyngeal cavity and the trachea. The tidal volume (VT) and respiratory frequency (f min(-1)) were recorded from the lower tracheal cannula. The respiratory minute volume (VE) was calculated, the action potentials from the right phrenic nerve were recorded and the inspiratory (TI) and expiratory (TE) periods and the mean inspiratory flow rate (VT/TI) were calculated. The larynx was insufflated at flow rates of 500mL min(-1) and 750mL min(-1), with 7 and 12% CO2-Air by means of a respiratory pump. RESULTS: Insufflation of the larynx, with both gas mixtures, decreased the f and VT significantly. The TI and TE were found to increase significantly due to the decreasing in f. There was a significant decrease in VT/TI ratio. Following bilateral midcervical vagotomy, on the passing of both gas mixtures, significant decreases were observed in the VT, and the responses of f, TI and TE were abolished. After cutting the superior laryngeal nerve, the responses of the VT to both gas mixtures were abolished. CONCLUSION: In conclusion, the results of this study purpose that the stimulation of the laryngeal mechanoreceptors by the effect of hyper- capnia decreases the activation of the respiratory center

Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance), histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber) were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9), mice were immunized with 10 æg ovalbumin (OVA, ip) on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 æg OVA at 3-day intervals. Control mice (N = 8) received saline under the same protocol. In the dexamethasone (N = 8) and LASSBio596 (N = 8) groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip) or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip) 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76 percent, respectively) compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

OBJETIVO: Avaliar os efeitos de duas diferentes doses de surfactante exógeno sobre a mecânica pulmonar e sobre a regularidade da expansão do parênquima pulmonar em coelhos recém-nascidos. MÉTODO: Coelhos recém-nascidos foram traqueostomizados e randomizados em quatro grupos de estudo: grupo-Controle, sem aspiração de mecônio; grupo MEC, com aspiração de mecônio e sem tratamento com surfactante exógeno; grupos S100 e S200, ambos com aspiração de mecônio e tratados respectivamente com 100 e 200 mg/kg de surfactante exógeno (produzido e fornecido pelo Instituto Butantan). Os animais dos 4 grupos foram ventilados por 25 minutos. A mecânica pulmonar foi avaliada a partir dos valores de complacência dinâmica, pressão ventilatória, volume-corrente e volume pulmonar máximo (curva P-V). A análise histológica foi feita calculando-se o diâmetro alveolar médio (Lm) e o índice de distorção através do desvio padrão do Lm. Utilizou-se ANOVA One Way com a = 0,05. RESULTADOS: Após 25 minutos de ventilação, os valores de complacência dinâmica (ml/cm H2O.kg) foram: 0,87± 0,07 (Controle); 0,49±0,04 (MEC*); 0,67±0,06 (S100) e 0,67±0,08 (S200) e de pressão ventilatória (cm H2O): 9,0± 0,9 (Controle); 16,5±1,7 (MEC*); 12,4±1,1 (S100) e 12,1±1,5 (S200). Ambos os grupos tratados tiveram padrão de expansão do parênquima mais homogêneo em relação aos animais não tratados: índice de distorção de 7,5± 1,9 (Controle); 11,3±2,5 (MEC*); 5,8±1,9 (S100) e 6,7±1,7 (S200) (*p < 0,05 vs outros grupos). CONCLUSÕES: Animais tratados com surfactante mostraram melhora significativa da mecânica pulmonar e maior homogeneidade do padrão de expansão pulmonar comparados ao grupo não tratado. Não houve influência das doses de surfactante utilizadas.

Pulmonary function profile in chronic congestive heart failure and the effect of ipratropium bromide.

Twenty-five symptomatic patients of chronic heart failure were subjected to spirometry to detect abnormalities of pulmonary function and to assess the effect of ipratropium bromide in reversing or minimising these abnormalities. All the patients exhibited abnormal pulmonary function manifesting as obstructive (15/25) or restrictive (10/25) ventilatory defect. There was overall improvement in lung functions with ipratropium bromide especially in those with obstructive ventilatory defects and mostly comprised of smokers. Forced expiratory volume in one second increased by 47.7 percent (p < 0.02), forced expiratory volume in one second/forced vital capacity ratio by 14.1 percent (p < 0.001) and maximal voluntary ventilation by 40.6 percent (p < 0.05) in these patients. It is concluded that ipratropium bromide can prove as a promising adjunctive therapeutic intervention in improving quality of life in patients of chronic congestive heart failure who are incapacitated by dyspnoea and have clearly documented ventilatory defects.

The effect of central and peripheral administration of acetylcholine and epinephrine on respiration.

The experiments were conducted in dogs anesthetized with Na-pentobarbital i.v. tidal volume (VT) and respiratory frequency (f min-1) were recorded. The central effects of acetylcholine (Ach) and epinephrine on respiration were investigated after injections of these substances directly into the cerebrospinal fluid by atlanto-occipital punction. The peripheral effects of Ach and epinephrine on respiration were studied after i.v. injections. Both central and peripheral administration of epinephrine caused significant increase in f min-1 and VT. After vagotomy the effects of centrally and peripherally administered epinephrine on f min-1 were abolished. The effect of central injection of epinephrine on VT persisted after vagotomy. The increase in VT in response to peripheral epinephrine administration was abolished by vagotomy. Both central and peripheral injection of Ach increased f min-1. In VT an initial decrease was followed by an increase. The initial decrease in VT was abolished by atropine. After vagotomy the effects of central and peripheral administration of Ach on f min-1 were abolished. The effects of central injection of Ach on VT persisted after vagotomy. Vagotomy abolished the effects of peripheral administration of Ach on VT.

Effects of nebulized beta 2-adrenergic agonists on pulmonary mechanics in anesthetized patients with chronic obstructive pulmonary disease.

We evaluated the effects of nebulized beta 2-adrenergic agonists on pulmonary mechanics in patients with COPD undergoing peripheral surgery with a standardized general anesthetic technique. Thirty males with COPD were randomized into one of three groups. Group I (control group; n = 10) received nebulized saline 3 ml, Group II (n = 10) received nebulized albuterol (2.5 mg in 3 ml), and Group III (n = 10) received nebulized metaproterenol (15 mg in 3 ml). At 20 min after tracheal intubation, the study drugs were nebulized over 20 min. Datex Capnomac Ultima monitor was used to measure pulmonary mechanics on a breath-by-breath basis. There was no difference between the three groups with respect to demographic data and preoperative respiratory parameters. A similar degree of DPH occurred with the initiation of mechanical ventilation in all three groups. Patients receiving nebulized bronchodilators (Groups II and III) displayed a significant decrease in DPH and an increase in total dynamic compliance. However, there were no differences in DPH and total dynamic compliance between Groups II and III. We conclude that nebulization of either albuterol or metaproterenol can alleviate DPH resulting from mechanical ventilation in anesthetized patients with COPD.

The effects of inhaled corticosteroids on chronic airflow limitation.

A placebo-controlled, double blind, cross-over study of inhaled budesonide was carried out to examine its effectiveness in the treatment of chronic airflow limitation (CAL). Fourteen patients (11 males, mean age 66 years) with stable CAL received placebo treatment for four weeks followed by inhaled budesonide 400 micrograms BD for eight weeks. Response was assessed by measuring forced expiratory volume in one second (FEV1). There was no significant improvement in the overall spirometric measurements and symptom scores except a reduction in daily peak expiratory flow rate fluctuation (p < 0.05). However, individual patients showed significant increase in FEV1. Two patients (14%) had greater than 30% increase in FEV1 in response to inhaled corticosteroids. This response could not be predicted from history of allergy, skin test, bronchial challenge test, peripheral blood or sputum eosinophilia. We conclude that only a minority of patients with stable CAL may respond to inhaled budesonide. Nonetheless, patients who are symptomatic despite treatment with maximum doses of bronchodilators may have a trial of inhaled corticosteroids in order to demonstrate any additional benefit.

Influence of pretreatment of carbamates on dynamic pulmonary mechanics in rats exposed to sarin aerosols.

The effect of pretreatment of two carbamates, pyridostigmine and physostigmine on dynamic pulmonary mechanics has been studied in rats exposed to sarin aerosols. Sign-free dose of pyridostigmine (0.075 mg/kg, i.m.) or physostigmine (0.1 mg/kg, i.m.) did not significantly alter the parameters of the dynamic pulmonary mechanics 20 min after treatment. However, sarin (51.2 mg/m3, for 15 min) depressed the respiratory rate, air flow and minute volume and enhanced the transthoracic pressure and tidal volume. Pretreatment with carbamates 20 min prior to sarin exposure significantly modified or counteracted the above induced changes. It is concluded that the protective effect of carbamates is mainly due to the correction of respiratory changes caused by sarin aerosols in rats.

Comparative efficacy of oral sustained released bronchodilator in stable asthmatics.

Double blind randomized trial of oral conventional and sustained release bronchodilators was undertaken to observe comparative efficacy in 30 patients older than 15 years. All cases selected were stable asthmatics at least for last 2 years having FEV1 improvement > or = 20%. Basal Pulmonary functions like FEV1, FVC and PEFR were recorded before and after drug administration at 1/2, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours. Four drug regimens were given as a single dose in the morning on randomized crossover manner on 1st, 4th, 7th and 10th days, sustained release theophylline 300 mg+salbutamol 4 mg (Drug I), salbutamol 4 mg + theophylline 300 mg (Drug II), salbutamol sustained released (asthalin SA) 8 mg (Drug III), salbutamol sustained released (ventorlin CR) 8 mg (Drug IV). Mean FEV1 changes observed at 0, 6 and 12 hours for all the drugs were compared which showed no statistical significance (t = 2.3876). Therefore, we conclude that using single dose fixed combination of oral salbutamol and aminophylline either in a plain or slow released form have no additive bronchodilator effect as compared to salbutamol alone in stable asthmatics.

Calcium channel blockers and terbutaline--a positive interaction.

The role of two calcium channel blockers, nifedipine and verapamil was investigated in patients of bronchial asthma. Both the drugs given orally produced an insignificant rise in PEFR, FEF25-75% and FEV1. Given along with terbutaline, however, these drugs produced significantly greater increase in PEFR, FEF25-75% and FEV1 as compared to patients receiving terbutaline alone. The two calcium channel blockers also inhibited the terbutaline induced tremors and palpitation.