Bronchial arterial imaging using helical computed tomography.

The bronchial arteries, which provide the systemic arterial supply to the lungs, are involved in a variety of disease processes in humans, including congenital disorders, infection, and pulmonary thromboembolism. In these conditions, the bronchial arteries hypertrophy and bronchial blood flow increases. Consequently, in many disorders, such as bronchiectasis, the bronchial arteries are a frequent source of haemoptysis, which may be massive and life-threatening. Evaluation of the bronchial circulation has typically required invasive imaging with angiography to determine the location of bleeding. Non-invasive assessment of bronchial arterial anatomy and morphology is currently being investigated with the use of helical computed tomography (CT). We evaluated eight patients with various lung diseases with helical CT (GE Medical Systems, LS16, Milwaukee, WI) to determine the imaging features of the bronchial circulation. Non-ionic contrast medium (iopromide) was injected intravenously (80-1000ml/30s) and scanning was triggered once contrast material was present in the pulmonary artery (average delay=15s) or ascending aorta (average delay=20s). Detector collimation (16-row unit) was 10mm. Imaging parameters included a section thickness of 0.6mm, kilovolt peak of 120, 150-440mA, pitch factor of 1.375, matrix of 512x512, and tube rotation time of 0.8s. The images were reconstructed and scanned isotropically (Advantage Workstation 4.1,GE Medical Systems). We conclude that helical computed tomography may provide a non-invasive means of evaluating the bronchial arteries and their role in pulmonary disease processes.

Bronchovascular responses to intravenous contrast media for helical CT pulmonary angiography.

CT angiography is now commonly used for the diagnosis of pulmonary embolism, but the contrast media used for imaging produces various hemodynamic changes. In this study, we investigated the bronchovascular and hemodynamic responses to intravenous iopromide, a non-ionic contrast agent used for pulmonary CT angiograms, in anesthetized, mechanically ventilated sheep (n = 6). Bronchial blood flow and cardiac output were measured with ultrasonic flow probes. Systemic and pulmonary arterial pressures were continuously monitored. Injections of 0.9% NaCl (120 ml over 30 s) or iopromide (300 mg/ml, 120 ml over 30 s) were given in random order in a peripheral vein with an angiogram infuser and hemodynamic changes were determined. After these parameters returned to baseline, the left pulmonary artery (LPA) was occluded with a snare and the animals were allowed to stabilize. Injections of NaCl and iopromide were repeated in random order as before. There were no significant hemodynamic effects with infusion of NaCl. With intact pulmonary vasculature, NaCl and iopromide did not cause significant changes in arterial blood gases, however, cardiac output (QT, L/min), mean systemic and pulmonary arterial pressures (PSA and PPA, Torr) increased and bronchovascular resistance (BVR, Torr x min/ml), decreased. Following LPA ligation, pH and PO2 significantly decreased over baseline, whereas PCO2 increased. After LPA ligation, iopromide produced a greater decrease in BVR as compared with preligation intact pulmonary vasculature. In conclusion, iopromide caused rapid hemodynamic changes and decreased BVR, likely secondary to osmolar stress. Bronchovascular effects were more pronounced after pulmonary arterial occlusion.

Controlled trial of inhaled fluticasone propionate in moderate to severe COPD.

Inhaled corticosteroids are often used in the treatment of stable chronic obstructive pulmonary disease (COPD), however, studies of these agents have had mixed results. Previous trials have often excluded subjects with bronchodilator response, have failed to evaluate effect on gas exchange, and have usually looked at only post- rather than prebronchodilator forced expiratory volume (FEV). Our objective was to better assess the efficacy of topical corticosteroids in the treatment of COPD. We used a prospective, randomized, double-blinded, placebo-controlled, crossover study at the Outpatient Department, Department of Veterans Affairs Medical Center. Thirty-six COPD patients with a mean (+/- SD) FEV1 of 1.10 +/- 0.43 L, with or without significant bronchodilator response participated in the study. Subjects received a 3-month course of inhaled fluticasone propionate (220 micro g/puff) or identical-appearing placebo by metered-dose inhaler at 2 puffs twice daily, followed by crossover to the alternative inhaler for an additional 3 months. Fluticasone treatment resulted in a higher prebronchodilator FEV1 (1.17 +/- 0.08 L [mean +/- SEM] versus 1.07 +/- 0.08 L, p = 0.001), a higher PaO2 (66.6 +/- 1.4 mmHg versus 63.6 +/- 1.6 mmHg, p = 0.002), and a better dyspnea score on the chronic respiratory questionnaire (3.70 +/- 0.18 versus 3.47 +/- 0.19, p = 0.03). A trend towards fewer exacerbations with fluticasone did not quite meet statistical significance (p = 0.11). Inhaled fluticasone over 3 months improved prebronchodilator airflow obstruction and oxygenation while decreasing dyspnea in moderate to severe COPD. Postbronchodilator FEV1 was not significantly changed.

Does sildenafil also improve breathing?

Sildenafil is being used by a number of patients with erectile dysfunction. Some of these patients also may have concomitant COPD. The effect of sildenafil on lung function is not known. Two patients with severe COPD and erectile dysfunction reported that their dyspnea improved when they took oral sildenafil for erectile dysfunction. Spirometry performed in these patients revealed an improvement in FEV(1) by 24% and 12%. This suggests that, in COPD patients, oral sildenafil does not have any deleterious effect on pulmonary function, and in some patients it may produce a modest improvement in FEV(1).

Effect of expiratory resistive loading on the noninvasive tension-time index in COPD.

Expiratory resistive loading (ERL) is used by chronic obstructive pulmonary disease (COPD) patients to improve respiratory function. We, therefore, used a noninvasive tension-time index of the inspiratory muscles (TT(mus) = I/PI(max) x TI/TT, where I is mean inspiratory pressure estimated from the mouth occlusion pressure, PI(max) is maximal inspiratory pressure, TI is inspiratory time, and TT is total respiratory cycle time) to better define the effect of ERL on COPD patients. To accomplish this, we measured airway pressures, mouth occlusion pressure, respiratory cycle flow rates, and functional residual capacity (FRC) in 14 COPD patients and 10 normal subjects with and without the application of ERL. TT(mus) was then calculated and found to drop in both COPD and normal subjects (P<0.05). The decline in TT(mus) in both groups resulted solely from a prolongation of expiratory time with ERL (P<0.001 for COPD, P<0.05 for normal subjects). In contrast to the COPD patients, normal subjects had an elevation in I and FRC, thus minimizing the decline in TT(mus). In conclusion, ERL reduces the potential for inspiratory muscle fatigue in COPD by reducing TI/TT without affecting FRC and I.

Comparative effects of alpha-receptor stimulation and nitrergic inhibition on bronchovascular tone.

Adrenergic agonists are known to influence bronchial blood flow and bronchovascular resistance. Recently, the nitrergic system has also been implicated in the control of bronchovascular tone. In this study, we compared the effects of the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) and the alpha(1)-receptor agonist phenylephrine on bronchovascular resistance in anesthetized sheep (n = 9). Bronchial blood flow, cardiac output, and systemic and pulmonary arterial pressures were continuously monitored. Phenylephrine (1.2-3.4 microg. kg(-1). min(-1)) was infused intravenously to increase mean systemic arterial pressure above 95 Torr for 10 min and then was discontinued. When hemodynamic parameters returned to baseline, nebulized phenylephrine (10 mg) was given over 10 min. When parameters again normalized, L-NAME (30 mg/kg) was infused intravenously over 1 min. Intravenous phenylephrine increased systemic vascular resistance by 40% at 10 min with no concurrent increase in bronchovascular resistance, but inhaled phenylephrine increased bronchovascular resistance by 66% at 10 min. By comparison, intravenous L-NAME produced a rapid and sustained fivefold increase in bronchovascular resistance at 10 min. We conclude that, although alpha-agonist stimulation has some influence on bronchovascular resistance in sheep, the nitrergic system has predominant control of bronchovascular tone.

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.

Effect of increased coronary venous pressure on left ventricular function in sheep.

We studied the effect of increased coronary venous pressure (Pcv) on left ventricular (LV) function in nine anesthetized open-chested sheep. Pcv was increased by inflating a balloon in the coronary sinus. LV function was estimated by measuring maximum rate of change in LV pressure (dP/dt max) and LV end-diastolic pressure (LVEDP). Left anterior descending (LAD) coronary artery blood flow was measured with an electromagnetic flow probe. A control group (n=6) was studied similarly except that Pcv was not elevated. After completion of the experiment, LV wet/dry weight ratios were measured to estimate LV myocardial water content. The balloon inflation increased Pcv from 8.6+/-1.1 to 23.8+/-1.7 mmHg (mean+/-SEM), which decreased dP/dt max from 1611+/-236 at baseline to 1041+/-210 after 120 min of increased Pcv (P < 0.05). The dP/dt max in the control group did not change significantly. Heart rate, LAD flow, LVEDP, and aortic pressures were similar in two groups but the LV water content was significantly higher (P < 0.05) in the experimental group (76.2+/-1.0 vs. 79.1+/-0.5%). These data suggest that acute increases in Pcv result in LV dysfunction and that coronary vascular congestion and myocardial edema may, at least in part, be responsible for this finding.

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.

Bronchial vascular congestion and angiogenesis.

The bronchial vasculature is the systemic arterial blood supply to the lung. Although small relative to the pulmonary blood flow, the bronchial vasculature serves important functions and is modified in a variety of pulmonary and airway diseases. Congestion of the bronchial vasculature may narrow the airway lumen in inflammatory airway diseases, and formation of new bronchial vessels (angiogenesis) is implicated in the pathology of a variety of chronic inflammatory, infectious and ischaemic pulmonary diseases. The remarkable ability of the bronchial vasculature to remodel has implications for disease pathogenesis. The contributions of the bronchial vasculature to the pathogenesis of pulmonary disease are reviewed in this article.

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.

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.

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.

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.

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.

Impaired bronchodilator response to albuterol in healthy elderly men and women.

BACKGROUND: Lymphocytes of normal elderly subjects and young asthmatics display dysfunctional beta-adrenoceptors. If beta-adrenoceptor dysfunction were found in senescent airways, it might help explain the pathogenesis of late onset asthma. METHODS: The bronchodilatory effects of albuterol after methacholine-provoked bronchoconstriction were compared in 17 healthy young (age 20 to 36 years) and 17 healthy elderly (age 60 to 76 years) volunteer subjects. Albuterol was inhaled via dosimeter (initially 7.8 micrograms, doubling every 7.5 min) with forced expiratory flow at 50% vital capacity (FEF50) measured prior to each dose. Albuterol sensitivity was expressed as the cumulative logarithm of the area under the FEF50 recovery curve (AUC); a greater AUC meant lower sensitivity. On another study day, spontaneous recovery from methacholine was assessed similarly. RESULTS: There was no intergroup difference in spontaneous recovery. Despite lower methacholine doses provoking similar (35%) FEF50 falls in elderly subjects, albuterol AUC was greater in elderly subjects (6,552%.min.microgram) than young subjects (3,922%.min microgram; p = 0.03). Multiple regression showed that AUC and age were related (p = 0.02). CONCLUSION: Airway beta 2-adrenoceptor responsiveness is diminished in old age, suggesting that airway beta-adrenoceptor dysfunction may be implicated in late-onset asthma.

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.