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Biomedical subjects

P Carvalho

Publications and source records attributed to P Carvalho.

At least 37 records · Page 2Linked to original sources

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta-agonists.

We studied the dose-dependent effects of inhaled isoetharine HCl, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Qbr) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Qbr. With a total dose of 17.5 mg, Qbr increased from baseline values of 22 +/- 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects beta-agonist-induced increases in Qbr, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased Qbr by approximately 80% of baseline, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (approximately 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Qbr in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.

Administration, Inhalation↗

Effect of aerosolized acetylcholine on bronchial blood flow.

We studied the effects of aerosolized as well as intravenous infusion of acetylcholine on bronchial blood flow in six anesthetized sheep. Intravenous infusion of acetylcholine, at a dose of 2 microg/kg, increased bronchial blood flow from 45 +/- 15 (SE) to 74 +/- 30 ml/min, and vascular conductance increased by 76 +/- 22%. In contrast, aerosolized acetylcholine at doses of 2 and 20 microg/kg decreased bronchial vascular conductance by approximately 10%. At an aerosolized dose of 200 microg/kg, the bronchial vascular conductance increased by approximately 15%, and there was no further increase in conductance when the aerosolized dose was increased to 2,000 microg/kg. Pretreatment of animals with a nitric oxide synthase inhibitor, Nomega-nitro-L-arginine methyl ester hydrochloride, partially blocked the vasodilatory effects of intravenous acetylcholine and completely blocked the vasodilatory effects of high-dose aerosolized acetylcholine. These data suggest that aerosolized acetylcholine does not readily penetrate the vascular wall of bronchial circulatory system and, therefore, has minimal vasodilatory effects on the bronchial vasculature.

Acetylcholine↗

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction.

We studied the effects of left pulmonary artery (LPA) ligation on the bronchial circulatory system (BCS) by using a sheep model. LPA was ligated in the newborn lambs soon after birth (n = 8), and when the sheep were approximately 3 yr of age anatomic studies revealed marked angiogenesis in BCS. Bronchial blood flow and cardiac output were studied by placing flow probes around the bronchial and pulmonary arteries in four adult sheep. After LPA ligation, bronchial blood flow increased from 35 +/- 6 to 134 +/- 42 ml/min in approximately 3 wk (P < 0.05). We also studied gas-exchange functions of BCS approximately 3 yr after the ligation of LPA in newborn lambs (n = 4) and used a control group (n = 12) in which LPA was ligated acutely. In the left lung, O2 uptake after acute ligation was 16 +/- 3 ml/min and was similar to the chronic model, whereas CO2 output in the control group was 27 +/- 3 ml/min compared with 79 +/- 12 ml/min in the chronic preparation (P < 0.05). We conclude that LPA ligation causes marked angiogenesis in BCS that is capable of performing some gas-exchange functions.

Animals↗

Nitric oxide and beta-adrenergic agonist-induced bronchial arterial vasodilation.

In anesthetized sheep, we measured bronchial blood flow (Qbr) by an ultrasonic flow probe to investigate the interaction between inhaled nitric oxide (NO; 100 parts/million) given for 5 min and 5 ml of aerosolized isoetharine (1.49 x 10(-2) M concentration). NO and isoetharine increased Qbr from 26.5 +/- 6.5 to 39.1 (SE) +/- 10.6 and 39.7 +/- 10.7 ml/min, respectively (n = 5). Administration of NO immediately after isoetharine further increased Qbr to 57.3 +/- 15.1 ml/min. NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester hydrochloride (L-NAME; 30 mg/kg, in 20 ml saline given i.v.) decreased Qbr to 14.6 +/- 2.6 ml/min. NO given three times alternately with isoetharine progressively increased Qbr from 14.6 +/- 2.6 to 74.3 +/- 17.0 ml/min, suggesting that NO and isoetharine potentiate vasodilator effects of each other. In three other sheep, after L-NAME three sequential doses of isoetharine increased Qbr from 10.2 +/- 3.4 to 11.5 +/- 5.7, 11.7 +/- 4.7, and 13.3 +/- 5.7 ml/min, respectively, indicating that effects of isoetharine are predominantly mediated through synthesis of NO. When this was followed by three sequential administrations of NO, Qbr increased by 146, 172, and 185%, respectively. Thus in the bronchial circulation, there seems to be a close interaction between adenosine 3',5'-cyclic monophosphate- and guanosine 3',5'-cyclic monophosphate-mediated vasodilation.

Animals↗

Management of bronchopleural fistula with a variable-resistance valve and a single ventilator.

Independent lung ventilation with two ventilators is sometimes used in the management of bronchopleural fistula (BPF). We describe a patient in whom gas flow through a large BPF was initially reduced, and subsequently eliminated, during differential lung ventilation using a single ventilator and a variable-resistance valve attached to one lumen of a bifurcated endotracheal tube.

Bronchial Fistula↗

Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax.

We studied the effects of unilateral tension pneumothorax and its release on bronchial and pulmonary arterial blood flow and gas exchange in 10 adult anesthetized and mechanically ventilated sheep with chronically implanted ultrasonic flow probes. Right pleural pressure (Ppl) was increased in two steps from -5 to 10 and 25 cmH2O and then decreased to 10 and -5 cmH2O. Each level of Ppl was maintained for 5 min. Bronchial blood flow, right and left pulmonary arterial flows, cardiac output (QT), hemodynamic measurements, and arterial blood gases were obtained at the end of each period. Pneumothorax resulted in a 66% decrease in QT, bronchial blood flow decreased by 84%, and right pulmonary arterial flow decreased by 80% at Ppl of 25 cmH2O (P < 0.001). At peak Ppl, the majority of QT was due to blood flow through the left pulmonary artery. With resolution of pneumothorax, hemodynamic parameters normalized, although abnormalities in gas exchange persisted for 60-90 min after recovery and were associated with a decrease in total respiratory compliance.

Animals↗

Controlled trial of oral prednisone in outpatients with acute COPD exacerbation.

Corticosteroids are often used in the outpatient treatment of acute exacerbation of chronic obstructive pulmonary disease (COPD). To date, there are few data documenting the benefit of this practice. The objective of this randomized, double-blind, placebo-controlled trial was to assess the efficacy of corticosteroids in the outpatient treatment of COPD exacerbations. Twenty-seven patients presenting with acute COPD exacerbation were studied. In addition to continuing their previous medications and increasing their use of beta-agonists, patients were randomized to receive a 9-d tapering dose of either oral prednisone or placebo. Treatment with prednisone rather than placebo resulted in a more rapid improvement in arterial PO2 (PaO2) (1.12 mm Hg/d versus -0.03 mm Hg/day; p = 0.002), alveolar-arterial oxygen gradient (A-aDO2) (-1.16 mm Hg/d versus -0.03 mm Hg/day; p = 0.04), FEV1 (0.05 L/d versus 0.00 L/d; p = 0.006), and peak expiratory flow (PEF) (0.15 L/s/d versus 0.04 L/s/d; p = 0.009). Prednisone also resulted in fewer treatment failures (p = 0.002) and in a trend toward more rapid improvement in dyspnea scale scores. Outpatient treatment of acute COPD exacerbation with prednisone accelerates recovery of PaO2, A-aDO2, FEV1, and PEF, reduces the treatment failure rate, and improves subjective dyspnea.

Administration, Oral↗

Effects of erythromycin on the rabbit pleura: its potential role as a pleural sclerosant.

Tetracycline (TCN) has been considered the agent of choice for pleurodesis in patients with symptomatic malignant pleural effusions and recurrent pneumothoraces. However, the intravenous form of TCN used for pleurodesis is no longer available. Erythromycin, like TCN, often produces irritation when administered intravenously. In view of these irritant properties, we tested the effect of erythromycin as a pleural sclerosant in rabbits as compared with TCN. Normal saline was used as a control. Adult rabbits weighing 2.5 to 3.0 kg underwent sterile placement of a silastic pleural tube in the right pleural space. Erythromycin (n = 17) or TCN (n = 6), each in doses of 35 mg/kg in 2 ml saline, was administered via the tube. Control animals (n = 6) received 2 ml saline. The chest tubes were left in place for removal of pleural fluid and to maintain lung expansion. Animals were killed 8 d after receiving the various treatments, and their pleural surfaces were examined grossly and histologically. Numerous adhesions were present between the visceral and parietal pleurae in all animals receiving erythromycin and TCN, but not in those receiving saline. On light microscopy, pleurae treated with erythromycin or TCN were histologically identical, showing inflammation, edema, and fibroblast proliferation in the submesothelial tissues. The saline-treated animals had a normal pleura. Because erythromycin produced pleural inflammation and adhesions within 8 d of treatment, we propose that it may have a potential role as a pleural sclerosant.

Animals↗

Independent lung ventilation with a single ventilator using a variable resistance valve.

Independent lung ventilation using two ventilators has been attempted in the treatment of acute respiratory failure due to unilateral lung disease. However, this method has been found to be cumbersome and difficult to use. We reasoned that a bifurcated endotracheal tube with a variable resistance valve may enable us to change the inspiratory airway pressures and, hence, the inspired tidal volume to one lung using a single ventilator. We tested this hypothesis in eight anesthetized sheep and created a bronchopleural fistula in one lung as a model of unilateral lung disease. A bifurcated endotracheal tube was placed to separate the ventilation to each lung and, through a "Y" connector, both right and left lungs were ventilated simultaneously with a single ventilator. A variable resistance valve was placed between the "Y" connector and the tube ventilating the experimental lung with bronchopleural fistula. With a ventilator-generated peak inspiratory pressure of 31 +/- 2 cm H2O, the airway pressure distal to the valve was randomly changed from 31 cm H2O to 23 +/- 2, 15 +/- 1, 8 +/- 1, and 0 cm H2O. This resulted in progressive diversion of tidal volume from the experimental lung to the control lung and an increase in exhaled tidal volume due to a decrease in air leak from the bronchopleural fistula. These data suggest that a variable resistance valve may be used for independent lung ventilation using a single ventilator.

Animals↗

Streptococcus pneumoniae-induced pulmonary hypertension and systemic hypotension in anesthetized sheep.

Because some patients with Streptococcus pneumoniae bacteremia may present with shock, we reasoned that this organism may produce substances that cause shock. To test this hypothesis, type III pneumococcus supernatant, suspended in 10 ml of sterile water, was infused over 1 min in 8 adult anesthetized sheep. Normal saline was used as a control and had no effect on any of the hemodynamic parameters. Infusion of supernatant resulted in a precipitous fall in cardiac output from a control value of 4.25 +/- 0.54 to 2.80 +/- 0.43 (SE) l/min, a fall in mean systemic arterial pressure from 70 +/- 4 to 49 +/- 8 mmHg, and an increase in the mean pulmonary arterial pressure from 13 +/- 2 to 23 +/- 4 mmHg within 1 min after the infusion was completed. The peak hemodynamic effects were observed at approximately 3 min and returned to normal within 10 min after the infusion was completed. The thromboxane B2 level increased from a control value of 10 +/- 5 to 156 +/- 43 pg/ml at 3 min after the infusion was completed and decreased to 63 +/- 34 pg/ml at 20 min. A second identical dose of pneumococcal supernatant, repeated within 2 h of the first dose, had no effect on hemodynamic variables. Pretreatment with indomethacin, 5 mg/kg body wt, completely blocked the hemodynamic effects of pneumococcal supernatant (n = 3 sheep). Thus, we conclude that S. pneumoniae supernatant contains substances that cause septic shock syndrome through the synthesis of arachidonic acid metabolites and that a sublethal dose of the supernatant causes rapid tachyphylaxis.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

Use of plasma for arterial blood gas analysis in leukemia.

A 63-year-old patient with chronic lymphocytic leukemia presented with severe hypoxemia. However, the patient's hemoglobin saturation, measured by an ear oximeter, was normal. Although his WBC count was approximately 1,000,000/microliters, hypoxemia could not be explained by the consumption of oxygen by leukocytes. Therefore, arterial blood gas values were analyzed in both plasma as well as in whole blood. The PaO2 in the plasma was much higher than in whole blood and corresponded with the hemoglobin saturation measured by the ear oximeter. These findings suggest that very high leukocyte counts may interfere with the measurement of oxygen tension and that plasma may be used for blood gas analysis in this situation.

Blood Gas Analysis↗

Effects of tube thoracostomy on pleural fluid characteristics in sheep.

We studied the pleural inflammatory response to tube thoracostomy by inserting an Argyle 32-Fr tube in the pleural space of 10 anesthetized sheep. An experimental pleural effusion was created by infusion of sterile normal saline (10 ml/kg) into the pleural space, and the animals were allowed to recover. Systemic blood and experimental pleural effusion (EPE) samples were obtained at time 0, 30 min, hourly for 6 h, and at 6-h intervals for a total of 48 h. EPE white cell count rose from 125 +/- 125 to 6,323 +/- 2,268/microliters (SE) at 6 h (P < 0.05) but showed marked variability at 42 and 48 h (P < 0.05), with values ranging from 8,000 to 22,000/microliters. The systemic white cell count rose from 5,195 +/- 914 to 9,640 +/- 1,110/microliters (P < 0.01) within the first 12 h and then remained stable. EPE protein increased from 0 +/- 0 to 3.73 +/- 0.2 g/dl at 48 h (P < 0.05). EPE lactate dehydrogenase rose from 44 +/- 12 IU/l to a peak of 638 +/- 55 IU/l at 24 h (P < 0.05). EPE glucose was significantly lower than serum glucose at 36, 42, and 48 h (P < 0.05). These data indicate that chest tube placement rapidly induces significant pleural inflammation and results in formation of a sterile exudate.

Animals↗

Monitoring in vivo lens changes. A comparative study with biochemical analysis of protein aggregation.

In this study the AA attempted to evaluate the relationship between lens optical density and lens fluorescence determined in vivo, with some specific (in vitro) biochemical changes occurring during cataract development. Special attention has been given to the comparison between diabetic and non diabetic cataracts. Prior to surgery all lenses were analysed by Scheimpflug photography to evaluate the topography of opacities and fluorescence distribution. Individual lenses were separated into cortex and nucleus and the amount of high molecular weight (HMW) protein aggregates was determined by FPLC (Fast Performance Liquid Chromatography). The results found in this study have shown that, as it would be expected, diabetic cataractous lenses present higher fluorescence levels than senile cataracts. It has also been shown that the increase in lens optical density, determined by Scheimpflug photography is clearly related to the increase in the amount of HMW-aggregates. Furthermore, in diabetic cataracts, a good correlation between protein aggregation and lens fluorescence determined in vivo has been found. Thus, it seems that in diabetic cataracts chemical or metabolic mechanisms leading to the production of fluorescent chromophores may be related to protein aggregation and therefore to the major processes involved in cataract development.

Aged↗

[The use of ergonovine in the hemodynamics laboratory].

In our department we have reviewed the use of ergonovine maleate as a provocative agent for inducing coronary spasm during coronary arteriography. From January 1978 to December 1991 the test has been performed in 116 patients. According to their symptoms, the patients were divided into 4 groups: (A) patients with exertional angina: 16 patients (13.8%), (B) patients with angina at rest: 64 patients (55.2%), (C) patients with atypical chest pain: 29 patients (25%), and (D) patients with previous myocardial infarct: 7 patients (6%). We have subdivided the patients with angina at rest, according to the electrocardiogram recorded during pain, into: (1) 16 patients with ST-segment elevation; (2) 14 patients with ST-segment depression or T wave inversion; (3) 5 patients with electrocardiogram unchanged during angina; (4) 29 patients with no electrocardiogram recorded during angina. In 67 patients (57.7%) the coronaries were normal, 17 patients (14.6%) had mild irregularities, 26 patients (22.4%) had non critical fixed obstructions (< or = 70%), and in 6 patients (3.5%) there were fixed coronary narrowings > or = 70%. The left ventricle was normal in 85 subjects (73.2%), hypo or akinetic in 31 (26.8%). After routine coronary angiography and ventriculography, ergonovine maleate, 0.05 up to 0.4 mg, was given intravenously. The ergonovine test was considered positive when a focal spasm narrowed a normal coronary artery, or one with a mild fixed obstruction (< or = 50%) to more than 70%, or when a 70% stenosis became occluded. The development of angina and/or electrocardiographic changes were not taken as a criteria of positivity. Thirteen tests (11.2%) were considered positive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Spectrophotometric analysis of sodium fluorescein aqueous solutions. Determination of molar absorption coefficient.

The usefulness of sodium fluorescein (SF) and related physical parameters were analysed. Two factors that may affect the molar absorption coefficient (epsilon) of this compound were the presence of impurities and the pH of the solution. As discrepant values can be found in the literature for that coefficient, a purification technique was used and SF quantification was performed according to sodium concentration determined by atomic absorption spectrophotometry. The molar absorption coefficient of the SF solution in phosphate buffer pH 7.4 was determined. To study the influence of pH on epsilon determination, absorption spectra at pH1, 3, 5, and 10 were also analysed.

Absorption↗

Pulmonary neoplasms simulating interlobar pleural effusions.

Loculated pleural effusions simulating neoplasms are a well known pitfall. The reverse is less well recognized. We describe three cases where tumours were initially diagnosed as loculated effusions. The differentiation of these two entities is discussed.

Diagnosis, Differential↗