Detection of A/H5N1 virus from asymptomatic native ducks in mid-summer in Egypt.

In spite of all the efforts to control H5N1 in Egypt, the virus still circulates endemically, causing significant economic losses in the poultry industry and endangering human health. This study aimed to elucidate the role of clinically healthy ducks in perpetuation of H5N1 virus in Egypt in mid-summer, when the disease prevalence is at its lowest level. A total of 927 cloacal swabs collected from 111 household and 71 commercial asymptomatic duck flocks were screened by using a real-time reverse transcription polymerase chain reaction. Only five scavenging ducks from a native breed in three flocks were found infected with H5N1 virus. This study indicates that H5N1 virus can persist in free-range ducks in hot weather, in contrast to their counterparts confined in household or commercial settings. Surveillance to identify other potential reservoirs is essential.

Pulmonary embolism: comparison of gadolinium-enhanced MR angiography with contrast-enhanced spiral CT in a porcine model.

RATIONALE AND OBJECTIVES: The purpose of this study was to compare gadolinium-enhanced magnetic resonance (MR) angiography with contrast material-enhanced computed tomography (CT) for the detection of small (4-5-mm) pulmonary emboli (PE), with a methacrylate cast of the porcine pulmonary vasculature used as the diagnostic standard. MATERIALS AND METHODS: In 15 anesthetized juvenile pigs, colored methacrylate beads (5.2 and 3.8 mm diameter-the size of segmental and subsegmental emboli in humans) were injected via the left external jugular vein. After embolization, MR angiographic and CT images were obtained. The pigs were killed, and the pulmonary arterial tree was cast in clear methacrylate, allowing direct visualization of emboli. Three readers reviewed CT and MR angiographic images independently and in random order. RESULTS: Forty-nine separate embolic sites were included in the statistical analysis. The mean sensitivity (and 95% confidence intervals) for CT and MR angiography, respectively, were 76% (68%-82%) and 82% (75%-88%) (P > .05); the mean positive predictive values, 92% (85%-96%) and 94% (88%-97%) (P > .05). In this porcine model, PE were usually seen as parenchymal perfusion defects (98%) with MR angiography and as occlusive emboli (100%) with CT. CONCLUSION: MR angiography is as sensitive as CT for the detection of small PE in a porcine model.

Spiral computed tomography is comparable to angiography for the diagnosis of pulmonary embolism.

The use of spiral computed tomography (CT) for the diagnosis of pulmonary embolism has been compared to angiography, the current gold standard. However, the accuracy of pulmonary angiography has never been evaluated against an independent gold standard. The aim of this study was to compare contrast-enhanced spiral CT to pulmonary angiography for the detection of subsegmental-sized pulmonary emboli by using a methacrylate cast of porcine pulmonary vessels as an independent gold standard. We studied 16 anesthetized, juvenile pigs and injected colored methacrylate beads (3.8 mm, small; 4.2 mm, large) via the jugular vein. After embolization spiral CT (3 mm and 1 mm collimation), and pulmonary angiography were performed. Pigs were killed and the pulmonary arterial tree was cast using methacrylate. Spiral CT and angiography were interpreted independently by two radiologists. Sensitivity and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 82% (73 to 88%), 87% (79 to 93%), 87% (79 to 93%) (p = 0.42). Positive predictive values and 95% confidence intervals for 3 mm and 1 mm collimation CT and angiography, respectively, were: 94% (86 to 94%), 81% (73 to 88%), and 88% (80 to 93%). There was no difference between spiral CT and angiography for detection of subsegmental-sized pulmonary emboli. We conclude that spiral CT is comparable to angiography for detection of pulmonary emboli.

Effect of contrast media on coronary vascular resistance: contrast-induced coronary vasodilation.

STUDY OBJECTIVES: To determine if the vasodilatory response to the intracoronary injection of ionic and nonionic contrast media in intact pigs is dependent on nitric oxide (NO). The mechanisms responsible for inducing the increase in coronary blood flow in response to the intracoronary injection of contrast media during angiography are still not entirely understood. There is evidence to suggest that the response could be partially mediated by NO. PARTICIPANTS: We studied 14 anesthetized, open-chested pigs receiving ventilation. MEASUREMENTS AND RESULTS: Changes in coronary blood flow and coronary vascular resistance were measured in response to the coronary artery injection of saline solution (0.5 mol/L, isosmolar with plasma) and three different contrast agents: meglumine sodium ioxaglate (Hexabrix; Mallinckrodt Medical; Point-Claire, Quebec, Canada), a low osmolar ionic contrast agent; iohexol (Omnipaque 300; Sanofi Winthrop; Markham, Ontario, Canada), a nonionic contrast agent; and diatrizoate meglumine 66%, diatrizoate sodium 10% (MD-76; Mallinckrodt Medical), an ionic contrast agent. Measurements were made during three experimental conditions: the coronary artery infusion of (1) saline solution, control; (2) L-nitro-arginine (LNNA; 10(-3) mol/L and 10(-2) mol/L), a competitive inhibitor of NO synthase; and (3)L-arginine 10(-1) mol/L, a substrate for NO synthase. The infusion of LNNA produced an increase in baseline coronary vascular resistance (p < 0.001), but it did not attenuate the vasodilatory response to the infusion of the contrast agents. Both the high and low osmolar ionic and nonionic contrast media caused a decrease in baseline coronary vascular resistance. For all three conditions, MD-76, which has the highest osmolality, produced the greatest decrease in coronary vascular resistance. CONCLUSION: The vasodilatory response of the coronary vasculature to contrast agents is directly related to osmolality and is not mediated by NO.

Effect of site and rate of contrast material injection on pulmonary vascular distention.

RATIONALE AND OBJECTIVES: The authors performed this study to determine if there were differences in vascular caliber measured on angiograms obtained with the injection protocol used for spiral computed tomography (CT) versus that used for pulmonary angiography. MATERIALS AND METHODS: The authors studied seven juvenile anesthetized pigs by using a prospective repeated measures experimental design. All pigs received injections of nonionic contrast material via catheters in the brachial vein, superior vena cava, main pulmonary artery, and left pulmonary artery. Weight-adjusted injection rates and volumes ranged from 0.05 mL/kg/sec (3.5 mL/sec, spiral CT protocol) to 0.56 mL/kg/sec (40 mL/sec, pulmonary angiography protocol). Heart rate and pulmonary artery and systemic artery pressures were recorded. During each injection, identically positioned pulmonary angiograms were obtained at full inspiration. Vessel diameters were measured at identical locations after each injection by two observers. The relationship between vessel diameter and hemodynamic parameters and injection site and rate was assessed with analysis of variance. RESULTS: At suspended full inspiration, no statistically significant difference (P > .05) in vessel diameter or hemodynamic parameters was found between the different injection sites or rates. There was no difference in vascular caliber between systole and diastole. CONCLUSION: The improved detection of subsegmental pulmonary emboli at pulmonary angiography compared with contrast material-enhanced spiral CT is not due to differences in vascular distention.

NO does not mediate inhibitory neural responses in sheep airway and bronchial vascular smooth muscle.

Endogenous nitric oxide (NO) influences acetylcholine-induced bronchovascular dilation in sheep and is a mediator of the airway smooth muscle inhibitory nonadrenergic, noncholinergic neural response in several species. This study was designed to determine the importance of NO as a neurally derived modulator of ovine airway and bronchial vascular smooth muscle. We measured the response of pulmonary resistance (RL) and bronchial blood flow (Qbr) to vagal stimulation in 14 anesthetized, ventilated, open-chest sheep during the following conditions: 1) control; 2) infusion of the alpha-agonist phenylephrine to reduce baseline Qbr by the same amount as would be produced by infusion of Nomega-nitro-L-arginine (L-NNA), a NO synthase inhibitor; 3) infusion of L-NNA (10(-2) M); and 4) after administration of atropine (1.5 mg/kg). The results showed that vagal stimulation produced an increase in RL and Qbr in periods 1, 2, and 3 (P < 0.01) that was not affected by L-NNA. After atropine was administered, there was no increase in Qbr or RL. In vitro experiments on trachealis smooth muscle contracted with carbachol showed no effect of L-NNA on neural relaxation but showed a complete blockade with propranolol (P < 0.01). In conclusion, the vagally induced airway smooth muscle contraction and bronchial vascular dilation are not influenced by NO, and the sheep's trachealis muscle, unlike that in several other species, does not have inhibitory nonadrenergic, noncholinergic innervation.

Distribution of blood flow and neutrophil kinetics in bronchial vasculature of sheep.

The bronchial circulation, as opposed to the pulmonary circulation, is the likely source of the edema and inflammatory cells that contribute to airflow obstruction and airway narrowing associated with asthma and pulmonary edema. The purpose of this study was to understand the mechanism of edema formation and inflammation in airway walls. Therefore, we sought first to determine the normal bronchial venous drainage pathways. In anesthetized, ventilated, open-chest sheep we measured the relative distribution of 51Cr-labeled red blood cells to the right and left ventricles after injection into the bronchial artery (n = 7). Using this information, we then studied the kinetics of leukocytes in the bronchial vascular bed. We measured the extraction of 111In-labeled neutrophils during their first pass through the microvasculature after injection into the bronchial artery or right ventricle (n = 6). In the first set of experiments, we found > 85% of the systemic blood flow to the lung returns to the left ventricle. In the second set of experiments, we found that extraction of neutrophils in the bronchial vasculature (50-60%) was less (P < 0.05) than that in the pulmonary vasculature (80%). This finding may be explained by differences in the anatomy and/or hydrodynamic dispersal forces between the pulmonary and bronchial vascular beds or may reflect sequestration of neutrophils within the pulmonary microvasculature while traversing bronchial-to-pulmonary anastomotic pathways.

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.

Bronchial vasodilatory response to ionic and nonionic contrast media.

It has recently been shown that bronchial arterial injection of conventional contrast medium causes a significant increase in bronchial blood flow (Qbr) and that this response is partially attenuated after infusion of N omega-nitro-L-arginine (L-NNA). However, the precise mechanism for this increase in Qbr is unknown. In this study we examined the effect of bronchial arterial injection of conventional ionic as well as nonionic contrast media. We measured Qbr in nine anesthetized, ventilated, open-chest sheep. Qbr was recorded before (baseline) and at the peak response to injection of 0.5 ml of either 0.9% saline (control; isosmolar with plasma), Omnipaque 300 (iohexol; nonionic), Conray 66 (sodium iothalamate; ionic), or 50% dextrose (viscous control). Measurements were made during a control period, after infusion of the alpha-agonist phenylephrine (5 x 10(-6) to 5 x 10(-7) M), and after bronchial arterial infusion of L-NNA (10(-2) M). The results were as follows: bronchial arterial injection of saline, Omnipaque, Conray, and dextrose caused an increase in Qbr (P < 0.05). During the control period, increases in peak Qbr on injection of saline, Omnipaque, Conray, and dextrose were 55 +/- 29, 112 +/- 62, 280 +/- 99, and 388 +/- 125% of baseline, respectively. Bronchial arterial infusion of L-NNA lowered baseline Qbr and partially attenuated the response to injection of saline, Omnipaque, and Conray (P < 0.05). Phenylephrine, in doses that decreased baseline Qbr to the same extent as did L-NNA, did not attenuate the bronchial vasodilation. There was a linear relationship between osmolality and the percentage increase in bronchial blood flow. We conclude that an osmolar stress is the trigger for the contrast-induced bronchial vasodilation and that the response is partially mediated by endothelial release of nitric oxide.

The anatomy and physiology of the bronchial circulation.

The origin and distribution of the bronchial vasculature vary considerably between and among species both at the macro- and microvascular level. Bronchial vessels usually originate from the aorta or intercostal arteries, entering the lung at the hilum, branching at the mainstem bronchus to supply the lower trachea, extrapulmonary airways, and supporting structures; this fraction of the bronchial vasculature drains into the right heart via systemic veins. Bronchial vessels also supply the intrapulmonary airways as far as the level of the terminal bronchioles where they form extensive anastomoses with the pulmonary vasculature; this systemic-to-pulmonary blood drains via pulmonary veins to the left heart. Repeated arborization of the bronchial artery along the length of the tracheal bronchial tree results in a vast increase in the total surface area of the vascular bed. The tracheal bronchial vasculature consists of a continuous dense network of subepithelial capillaries that converge to form venules extending to a deeper plexus of larger venules and arterioles on the adventitial side of the smooth muscle. Innervation is under the control of vasodilatory parasympathetic nerves that release acetylcholine and vasoactive intestinal polypeptide; vasoconstrictor sympathetic nerves that release norepinephrine and neuropeptide Y; and sensory nerves that release substance P, neurokinin A, and calcitonin gene-related peptide, all of which are vasodilators. Mechanical factors such as the downstream pressure and alveolar pressure also influence the distribution of blood flow through the tracheal bronchial vasculature.

Bronchial arterial response to contrast medium.

RATIONALE AND OBJECTIVES: Contrast agents have been shown to produce vasodilatory responses in several vascular beds. To our knowledge, however, their effect on the bronchial vasculature has not been examined. Clinically, contrast-induced bronchial vasodilation could potentially exacerbate life-threatening pulmonary hemorrhage during bronchial angiography for hemoptysis. In the current study, we systematically measured the bronchial vasodilatory response to diatrizoate meglumine 66% and diatrizoate sodium 10% (MD-76) and examined whether vasodilation would be mediated by nitric oxide (NO). METHODS: We measured bronchial blood flow in seven anesthetized, ventilated, open-chested sheep using an ultrasonic flow probe placed around the bronchial artery. Bronchial blood flow was recorded before and after injection of 2 ml MD-76 into the bronchial artery. The protocol was repeated after 20 min infusion of N omega-nitro-L-arginine (L-NA; 10(-2) mol/l), an NO-synthase inhibitor, into the bronchial artery. RESULTS: There was a 45 +/- 8 ml/min increase (p < .01) in bronchial blood flow after injection of MD-76, which was reduced to 20 +/- 6 ml/min (p < .01) after infusion of L-NA. CONCLUSION: Bronchial arterial injection of MD-76 results in a consistent increase in bronchial blood flow that is mediated partly by NO.

Pulmonary arterial contribution to airway blood flow after lung transplantation in dogs.

Despite the improved success of lung transplantation, ischemia of the donor bronchus continues to be the most important factor influencing airway healing. Recent studies have shown that at the level of the mainstem bronchi the pulmonary contribution to the airway blood flow may be equivalent to or greater than the systemic contribution and could therefore assist early healing of the newly anastomosed bronchus and, in addition, might facilitate the improved healing associated with omentopexy. The aim of this study was to measure the pulmonary contribution to airway blood flow in dogs after allotransplantation of the left lung and to determine whether omentopexy might improve the healing process. Using the radioactive microsphere technique, we measured the pulmonary contribution to airway blood flow in 25 dogs 1 week after allotransplantation of the left lung. Half the dogs had an omental wrap around the anastomotic site. Results showed that pulmonary blood flow increased progressively from lower trachea to distal mainstem bronchus and supplied the left mainstem bronchus above as well as below the anastomotic site. Omentopexy did not increase flow or enhance healing.

Endogenous nitric oxide influences acetylcholine-induced bronchovascular dilation in sheep.

To test whether endogenous endothelial nitric oxide (NO) influences baseline bronchial vascular tone and mediates acetylcholine (ACh)-induced bronchial vascular dilation and/or modulates bronchoconstriction in ovine airways, we studied anesthetized ventilated open-chest sheep and measured bronchial blood flow (Qbr) and pulmonary resistance (RL). In six sheep we measured the response of Qbr and RL to the dose of ACh required to produce 50% of the maximal increase in Qbr at baseline during infusion of the NO synthase inhibitor NG-nitro-L-arginine (L-NNA; 10(-2) M). Infusion of L-NNA decreased both the baseline Qbr (28 +/- 13 to 8 +/- 2 ml/min, P < 0.01) and the change in Qbr (delta Qbr) from the baseline value (84 +/- 42 to 33 +/- 18 ml/min, P < 0.05). There was no difference in baseline RL or in the response of RL to ACh at any time. In another six sheep, phenylephrine (5 x 10(-6) to 5 x 10(-7) M) decreased baseline Qbr (22 +/- 6 to 10 +/- 3 ml/min, P < 0.05) but not delta Qbr (62 +/- 13 to 66 +/- 21 ml/min, not significant). Infusion of L-NNA in these sheep decreased the baseline Qbr to a similar extent (11 +/- 5 ml/min) and also decreased delta Qbr (42 +/- 16 ml/min, P < 0.05). We conclude that endogenous endothelial NO influences baseline vascular tone and ACh-induced vasodilation of the ovine bronchial vasculature but has no effect on baseline RL or ACh-induced bronchoconstriction.

Measurement of lung water content and pleural pressure gradient with magnetic resonance imaging.

The aim of this study was to develop a magnetic resonance (MR) sequence capable of measuring water content and the gravity-dependent gradient in lung density in normal lung. First, the MR signal from excised normal pig lung was characterized using a 2.1 T nuclear magnetic resonance (NMR) spectrometer. A multiecho sequence was then developed on a 0.15 T Picker MR scanner. This sequence was validated in excised normal pig lung by comparison with gravimetric lung water content. Finally, this sequence was used in five normal volunteers in the prone and supine positions during quiet breathing and in the supine position at total lung capacity (TLC). The ratio of lung water measured by MR and gravimetric techniques was 0.95 +/- 0.03. There was no significant difference in average lung density in the prone (0.21 +/- 0.03 g/ml) and in the supine (0.20 +/- 0.03 g/ml) positions. Lung density decreased at TLC (0.12 +/- 0.01 g/ml) (p < 0.01). Gradients in lung density were visible in all prone and supine scans at functional residual capacity (FRC), and on average the gradients were decreased by 90% at TLC. The average estimated pleural pressure gradient in the prone position was 0.13 +/- 0.08 cm H2O/cm lung and in the supine position was 0.38 +/- 0.23 cm H2O/cm lung. MRI allows measurement of lung water content and pleural pressure gradient.

Airway blood flow and bronchovascular congestion in sheep.

Vascular congestion could play an important role in causing airway narrowing in asthma. However, the effects of altered bronchial vascular volume and blood flow on airway morphology and pulmonary resistance have not been studied. The aim of this study was to measure airway calibre and vascular volume during inhalation of reputed dilators and constrictors of the airway vasculature in sheep. After baseline measurements of pulmonary resistance (RL) and airway blood flow (Qaw), anaesthetized sheep inhaled an aerosol of either: 0.9% saline (n = 6); histamine 16 mg.ml-1 (n = 5); phenylephrine 0.1-10 mg.ml-1 (n = 6), or methoxamine 1 mg.ml-1 (n = 5). RL and Qaw were measured at the time of peak bronchoconstriction, and the sheep were rapidly killed and lung blood loss prevented. Right lung Qaw was calculated and left lung processed for histology; measurements of cartilaginous airway size, wall thickness and fraction of the wall occupied by blood were made using morphometric techniques. Results showed that 20-30% of the airway wall was occupied by blood vessels. Inhalation of histamine caused an increase in Qaw and RL, and a 50% increase in the vascular volume fraction of the airway wall, whereas inhaled alpha-agonists did not reduce Qaw or vascular volume fraction. We conclude that the major cause of airway narrowing after inhalation of histamine is contraction of the smooth muscle, and the bronchovascular congestion contributes little to airway narrowing in cartilaginous airways of sheep. In addition inhaled alpha-agonists do not constrict the bronchial microvasculature under baseline conditions. Therefore, our results do not support the hypothesis that protection against bronchoconstriction provided by alpha-agonists is due to vasoconstriction.

Blood flow to the trachea and bronchi: the pulmonary contribution.

It is generally assumed that when pulmonary vascular pressures are normal the pulmonary contribution to central airway blood flow (Qp) is negligible compared with systemic blood flow (Qs). However, it has been suggested in recent reports that a substantial portion of central airway blood flow is Qp. We have attempted to confirm whether there is a pulmonary contribution to central airway blood flow and to describe how it is anatomically distributed. Measurements of Qp were made using the radioactive microsphere technique in anesthetized ventilated dogs (n = 7) and sheep (n = 6). Qs to the central airways was also measured in another group of sheep (n = 10). At the end of each study, animals were killed and the lungs and trachea were excised. Qp to the upper and lower trachea, mainstem bronchi, and lobar bronchi was calculated, and the relative distribution of Qp and Qs to mucosa, cartilage, and adventitia was determined. Results showed a progressive increase (P < 0.01) in Qp (in ml.min-1 x 100 g-1) from upper trachea to lobar bronchi in both dogs and sheep. Qp and Qs supplied mainly the airway adventitia and the mucosa, respectively. Expressed as a percentage, 89 +/- 4% (SE) of Qp was to the adventitia and 0.1 +/- 0.07% was to the mucosa (P < 0.01), whereas 60 +/- 3.2% of Qs was to the mucosa and 22 +/- 4.6% was to the adventitia. In conclusion, in dogs and sheep there is a pulmonary contribution to central airway blood flow that increases from upper trachea to lobar bronchi and that supplies mainly the peritracheal adventitia.

Bronchial vascular occlusion does not attenuate or accentuate oleic acid lung injury in anesthetized sheep.

To determine if bronchial blood flow affects the consequences of acute pulmonary vascular injury, we studied oleic acid lung injury in 12 anesthetized sheep. In six sheep (group 1), we injected 2 ml of ethanol directly into the bronchoesophageal artery to decrease bronchial blood flow. In the control sheep (group 2), we injected 2 ml of normal saline. One hour later, oleic acid (0.1 ml/kg) was injected into the right ventricle in both groups. We measured hemodynamics and lung mechanics at baseline, 1 h after injection into the bronchoesophageal artery but just before the injection of oleic acid, and 3 h after injection of oleic acid. We measured bronchial blood flow at baseline and 3 h after injection of oleic acid and extravascular lung water at 3 h after injection of oleic acid. One hour after injection of ethanol or saline into the bronchoesophageal artery, hemodynamics and lung mechanics did not change. Three hours after injection of oleic acid, systemic arterial pressure decreased, pulmonary arterial pressure increased, cardiac output decreased, dynamic compliance decreased, pulmonary resistance increased, arterial oxygen tension decreased, and extravascular lung water was greater than normal. There were no differences in these measurements between the two groups. However, bronchial blood flow decreased only in group 1. We conclude that decreasing bronchial blood flow does not attenuate or accentuate the consequences of oleic acid lung injury.

Blood flow distribution to upper airway muscles.

Radiolabeled (15-microns) microspheres were used to measure blood flow to upper airway muscles [alae nasi (AN), intrinsic laryngeal, tongue, cervical strap, and hyoid musculature], diaphragm (DI), and parasternals (PS) during spontaneous breathing in 24 anesthetized tracheotomized supine dogs. Six dogs were also studied while -28 +/- 3 (SE) cmH2O tracheal airway pressure was generated against an inspiratory resistance (IR) (upper airway bypassed). Blood flow to posterior cricoarytenoid muscle (PCA) [24.0 +/- 2.1 (SE) ml.min-1.100 g-1] was greater than that to DI (18.0 +/- 2.3 ml.min-1.100 g-1) and comparable to that to PS (21.4 +/- 2.9 ml.min-1.100 g-1). Blood flow per unit weight did not differ between AN, tongue muscles, laryngeal adductors, cervical strap muscles, and cricothyroid (CT). Average blood flow to these muscles was only 8.0 +/- 0.8 ml.min-1.100 g-1. With the exception of CT, blood flow to these upper airway muscles was less than that to DI and PCA. Relative to blood flow during spontaneous breathing, IR loading increased blood flow to AN by a factor of 7.5, to PCA by 3.4, to DI by 3.2 and to PS by 1.9. There was no change in blood flow in the other muscles during loading. Our results show that at rest blood flow to main glottic dilator (PCA) is similar to that to main inspiratory muscles. Furthermore, in response to an IR load, blood flow to PCA and AN increased by an equivalent or greater amount than that to DI.(ABSTRACT TRUNCATED AT 250 WORDS)