Histamine-induced pulmonary edema distal to pulmonary arterial occlusion

Histological studies provide evidence that the bronchial veins are a site of leakage in histamine-induced pulmonary edema, but the physiological importance of this finding is not known. To determine if a lung perfused by only the bronchial arteries could develop pulmonary edema, we infused histamine for 2 h in anesthetized sheep with no pulmonary arterial blood flow to the right lung. In control sheep the postmortem extravascular lung water volume (EVLW) in both the right (occluded) and left (perfused) lung was 3.7 +/- 0.4 ml X g dry lung wt-1. Following histamine infusion, EVLW increased to 4.4 +/- 0.7 ml X g dry lung wt-1 in the right (occluded) lung (P less than 0.01) and to 5.3 +/- 1.0 ml X g dry wt-1 in the left (perfused) lung (P less than 0.01). Biopsies from the right (occluded) lungs scored for the presence of edema showed a significantly higher score in the lungs that received histamine (P less than 0.02). Some leakage from the pulmonary circulation of the right lung, perfused via anastomoses from the bronchial circulation, cannot be excluded but should be modest considering the low pressures in the pulmonary circulation following occlusion of the right pulmonary artery. These data show that perfusion via the pulmonary arteries is not a requirement for the production of histamine-induced pulmonary edema.     

Ligation of the bronchial artery in sheep attenuates early pulmonary changes following exposure to smoke.

Smoke inhalation can produce acute pulmonary edema. Previous studies have shown that the bronchial arteries are important in acute pulmonary edema occurring after inhalation of a synthetic smoke containing acrolein, a common smoke toxin. We hypothesized that inhalation of smoke from burning cotton, known to contain acrolein, would produce in sheep acute pulmonary edema that was mediated by the bronchial circulation. We reasoned that occluding the bronchial arteries would eliminate smoke-induced pulmonary edema, whereas occlusion of the pulmonary artery would not. Smoke inhalation increased lung lymph flow from baseline from 2.4 +/- 0.7 to 5.6 +/- 1.2 ml/0.5 h at 30 min (P < 0.05) to 9.1 +/- 1 ml/0.5 h at 4 h (P < 0.05). Bronchial artery ligation diminished and delayed the rise in lymph flow with baseline at 2.8 +/- 0.7 ml/0.5 h rising to 3.1 +/- 0. 8 ml/0.5 h at 30 min to 6.5 +/- 1.5 ml/0.5 h at 240 min (P < 0.05). Wet-to-dry ratio was 4.1 +/- 0.2 in control, 5.1 +/- 0.3 in smoke inhalation (P < 0.05), and 4.4 +/- 0.4 in bronchial artery ligation plus smoke-inhalation group. Smoke inhalation after occlusion of the right pulmonary artery resulted in a wet-to-dry ratio after 4 h in the right lung of 5.5 +/- 0.8 (P < 0.05 vs. control) and in the left nonoccluded lung of 5.01 +/- 0.7 (P < 0.05). Thus the bronchial arteries may be major contributors to acute pulmonary and airway edema following smoke inhalation because the edema occurs in the lung with the pulmonary artery occluded but not in the lungs with bronchial arteries ligated.     

Sinoaortic deafferentation reduces intrapulmonary shunt in dogs with oleic acid lung injury

Hypoxic stimulation of the peripheral chemoreceptors has been reported to inhibit hypoxic pulmonary vasoconstriction. To evaluate the pathophysiological importance of this observation, we investigated the effects of surgical peripheral chemoreceptor denervation on pulmonary vascular tone and gas exchange in 17 pentobarbital-anesthetized dogs with oleic acid pulmonary edema. Pulmonary arterial pressure-cardiac index (Ppa/Q) plots, blood gases, and intrapulmonary shunt measured by the SF6 method were obtained at base line, after peripheral chemodenervation (n = 9) or after sham operation (n = 8), and again after 0.09 ml.kg-1 intravenous oleic acid. Over the range of Q studied (2-5 l.min-1.m-2), Ppa/Q plots were best fitted as first-order polynomials in most dogs in all experimental conditions. Chemoreceptor denervation increased Ppa at the lowest Q, while sham operation did not affect the Ppa/Q plots. Oleic acid increased Ppa over the entire range of Q and increased intrapulmonary shunt. This latter was measured at identical Q during the construction of the Ppa/Q plots. Chemoreceptor-denervated dogs, compared with sham-operated dogs, had the same pulmonary hypertension but lower intrapulmonary shunt (36 +/- 4 vs. 48 +/- 5%, means +/- SE, P less than 0.04) and venous admixture (43 +/- 4 vs. 54 +/- 3%, P less than 0.02). We conclude that in intact dogs chemoreceptor denervation attenuates the rise in intrapulmonary shunt after oleic acid lung injury. Whether this improvement in gas exchange is related to an enhanced hypoxic pulmonary vasoconstriction is uncertain.     

Developmental changes in arginase expression and activity in the lung

Arginases compete with nitric oxide (NO) synthases for L-arginine as common substrate. Pulmonary vascular and airway diseases in which arginase activity is increased are associated with decreased NO production and reduced smooth muscle relaxation. The developmental patterns of arginase activity and type I and II isoforms expression in the lung have not been previously evaluated. Hypothesizing that lung arginase activity is developmentally regulated and highest in the fetus, we measured the expression of both arginase isoforms and total arginase activity in fetal, newborn, and adult rat lung, pulmonary artery, and bronchial tissue. In addition, intrapulmonary arterial muscle force generation was evaluated in the absence and presence of the arginase inhibitor Nomega-hydroxy-nor-L-arginine (nor-NOHA). Arginase II content, as well as total arginase activity, was highest in fetal rat lung, bronchi, and pulmonary arterial tissue and decreased with age (P<0.05), and its lung cell expression was developmentally regulated. In the presence of nor-NOHA, pulmonary arterial force generation was significantly reduced in fetus and newborn (P<0.01). No significant change in force generation was noted in bronchial tissue following arginase inhibition. In conclusion, arginase II is regulated developmentally, and both expression and activity are maximal during fetal life. We speculate that the maintenance of a high pulmonary vascular resistance and decreased lung NO production prenatally may, in part, be dependent on increased arginase expression and/or activity.     

Acute increases in anastomotic bronchial systemic to pulmonary blood flow due to generalized lung injury

Since pulmonary blood flow to regions involved in adult respiratory disease syndrome (ARDS) is reduced by hypoxic vasoconstriction, compression by cuffs of edema, and local thromboses, we postulated that the bronchial circulation must enlarge to provide for the inflammatory response. We measured anastomotic bronchial systemic to pulmonary blood flow [QBr(s-p)] serially in a lung lobe in 31 open-chest dogs following a generalized lobar injury simulating ARDS. The pulmonary circulation of the weighed left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in anesthetized dogs. QBr(s-p) was measured from the amount of blood which overflowed from this closed vascular circuit corrected by any changes in the lobe weight. The LLL was ventilated with 5% CO2 in air. The systemic blood pressure (volume infusion), gases, and acid-base status (right lung ventilation) were kept constant. We injured the LLL via the airway by instilling either 0.1 N HCl or a mixture of glucose and glucose oxidase or via the pulmonary vessels by injecting either alpha-naphthylthiourea or oleic acid into the LLL pulmonary artery. In both types of injury, there was a prompt rise in QBr(s-p) (mean rise = 247% compared with control), which was sustained for the 2 h of observation. The cause of this increase in flow was studied. Control instillation of normal saline into the airways or into the pulmonary vessels did not change QBr(s-p) nor did a similar increase in lobar fluid (weight) due to hydrostatic edema. Neither cardiac output nor systemic blood pressure increased.(ABSTRACT TRUNCATED AT 250 WORDS)     

Measurement of bronchial blood flow with radioactive microspheres in awake sheep

Distribution of bronchial blood flow was measured in unanesthetized sheep by the use of two modifications of the microsphere reference sample technique that correct for peripheral shunting of microspheres: 1) A double microsphere method in which simultaneous left and right atrial injections of 15-microns microspheres tagged with different isotopes allowed measurement of both pulmonary blood flow and shunt-corrected bronchial blood flow, and 2) a pulmonary arterial occlusion method in which left atrial injection and transient occlusion of the left pulmonary artery prevented delivery to the lung of microspheres shunted through the peripheral circulation and allowed systemic blood flow to the left lung to be measured. Both methods can be performed in unanesthetized sheep. The pulmonary arterial occlusion method is less costly and requires fewer calculations. The double microsphere method requires less surgical preparation and allows measurement without perturbation of pulmonary hemodynamics. There was no statistically significant difference between bronchial blood flow measured with the two methods. However, total bronchial blood flow measured during pulmonary arterial occlusion (1.52 +/- 0.98% of cardiac output, n = 9) was slightly higher than that measured with the double microsphere method (1.39 +/- 0.88% of cardiac output, n = 9). In another series of experiments in which sequential measurements of bronchial blood flow were made, there was a significant increase of 15% in left lung bronchial blood flow during the first minute of occlusion of the left pulmonary artery. Thus pulmonary arterial occlusion should be performed 5 s after microsphere injection as originally described by Baile et al. (1).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lack of alveolar O2 during lung reperfusion does not decrease edema formation

We previously reported that pulmonary arterial occlusion for 48 h followed by 4 h of reperfusion in awake dogs results in marked edema and inflammatory infiltrates in both reperfused and contralateral lungs (Am. Rev. Respir. Dis. 134: 752-756, 1986; J. Appl. Physiol. 63: 942-950, 1987). In this experiment we study the effects of alveolar hypoxia on this injury. Anesthetized dogs underwent thoracotomy and occlusion of the left pulmonary artery. Twenty-four hours later the dogs were reanesthetized, and a double-lumen endotracheal tube was placed. The right lung was continuously ventilated with an inspiratory O2 fraction (FIO2) of 0.35. In seven study animals the left lung was ventilated with an FIO2 of 0 for 3 h after the left pulmonary artery occluder was removed. In six control animals the left lung was ventilated with an FIO2 of 0.35 during the same reperfusion period. Postmortem bloodless wet-to-dry weight ratios were 5.87 +/- 0.20 for the left lower lobe and 5.32 +/- 0.12 for the right lower lobe in the dogs with hypoxic ventilation (P less than 0.05 for right vs. left lobes). These values were not significantly different from the control dog lung values of 5.94 +/- 0.22 for the left lower lobe and 5.11 +/- 0.07 for the right lower lobe (P less than 0.05 for right vs. left lobes). All values were significantly higher than our laboratory normal of 4.71 +/- 0.06. We conclude that reperfusion injury is unaffected by alveolar hypoxia during the reperfusion phase.     

Lung mechanics in hypervolemic pulmonary edema.

Extravascular thermal volume of the lung (ETVL) is a double indicator dilution technique of use in measuring pulmonary edema. ETVL and lung mechanics measurements were followed to find a less invasive monitor of pulmonary edema than the double indicator dilution technique. Pulmonary edema was induced by overloading the dogs' circulation with dextran. Phases of overload were defined on the basis of a previous electron microscopic study (Noble et al., Can. Anesthetists Soc. J. 21:275, 1974) of lung biopsies relating anatomic changes to physiologic measurements of ETVL and central blood volume (CBV). Congestion occurred when CBV was elevated and ETVL was not, interstitial edema when ETVL was elevated but smaller than 60% above control and alveolar edema when ETVL greater than 85% above control. Once the dogs were in alveolar edema, they were mechanically ventilated with 4, 8, 12, and 16 cmH2O end-tidal pressure (CPPV). Mean functional residual capacity (FRC) for all 15 dogs did not change up to the time CPPV was applied. Pulmonary resistance did not rise until alveolar edema was present. Once in pulmonary edema, lung compliance always fell as lung water increased. In individual dogs, the compliance fall was directly proportional to the rising lung water. However, the variations in slope and beginning point among dogs made it difficult to predict the amount of lung water from dynamic compliance values. PaO2 fell markedly in alveolar edema as a result of a widened A-a gradient. CPPV did not decrease lung water but did increase FRC and PaO2.     

Bronchial collateral vessel micropuncture pressure in postobstructive pulmonary vasculopathy.

Postobstructive pulmonary vasculopathy, produced by chronic ligation of one pulmonary artery, markedly increases bronchial blood flow. Previously, using arterial and venous occlusion, we determined that bronchial collaterals enter the pulmonary circuit at the distal end of the arterial segment. In this study, we tested the hypothesis that pressure in bronchial collaterals (Pbr) closely approximates that at the downstream end of the arterial segment (Pao). We pump perfused [111 +/- 10 (SE) ml/min] left lower lobes of seven open-chest live dogs 3-15 mo after ligation of the left main pulmonary artery. Bronchial blood flow was 122 +/- 16 ml/min. We measured pulmonary arterial and venous pressures and, by arterial and venous occlusion, respectively, Pao and the pressure at the upstream end of the venous segment (Pvo). Pbr was obtained by micropuncture of 34 pleural surface bronchial vessels 201 +/- 16 microns in diameter. We found that Pbr (14.4 +/- 1.0 mmHg) was similar to Pao (15.0 +/- 0.8 mmHg) but differed significantly (P < 0.01) from Pvo (11.3 +/- 0.5 mmHg). In addition, Pbr was independent of systemic arterial pressure and bronchial vessel diameter. Light and electron microscopy revealed that, in the lobes with the ligated pulmonary artery, the new bronchial collaterals entered the thickened pleura from the parenchyma via either bronchovascular bundles or interlobular septa and had sparsely muscularized walls. We conclude that, in postobstructive pulmonary vasculopathy, bronchial collateral pressure measured by micropuncture is very close to the pressure in precapillary pulmonary arteries and that most of the pressure drop in the bronchial collaterals occurs in vessels > 350 microns in diameter.     

Bronchial blood flow affects recovery from constriction in dog lung periphery

We investigated the effect of eliminating the bronchial circulation on recovery time from intravenous histamine challenge in canine lung periphery. Results from animals with intact bronchial circulations were compared with a second group in which the left lower lobe was isolated in situ. The pulmonary artery to this lobe was perfused and a bronchoscope was wedged in a small airway, which provided an index of resistance to airflow through the collateral system. The lobe was challenged with intravenous histamine, and the time constant of recovery (tau) from bronchoconstriction was measured. With or without pulmonary blood flow, elimination of the bronchial circulation increased tau 44.4 and 48.5%, respectively. This increase was similar to that found by stopping pulmonary blood flow alone (56.5%). Histamine challenges were also performed in sympathectomized or vagotomized animals with intact bronchial circulations. Neither of these conditions increased tau. We conclude that blood flow through the bronchial circulation affects the recovery time from intravenous histamine challenge in the lung periphery to a degree similar to that of the pulmonary circulation.     

Bronchial artery ligation modifies pulmonary edema after exposure to smoke with acrolein

Pulmonary edema can follow smoke inhalation and is believed to be due to the multiple chemical toxins in smoke, not the heat. We have developed a synthetic smoke composed of aerosolized charcoal particles to which one toxin at a time can be added to determine whether it produces pulmonary edema. Acrolein, a common component of smoke, when added to the synthetic smoke, produced a delayed-onset pulmonary edema in dogs in which the extravascular lung water (EVLW) as detected by a double-indicator technique began to rise after 42 +/- 2 (SE) min from 148 +/- 16 to 376 +/- 60 ml at 165 min after smoke exposure. The resulting pulmonary edema was widespread macroscopically but appeared focal microscopically with fibrin deposits in alveoli adjacent to small bronchi and bronchioles. Bronchial vessels were markedly dilated and congested. Monastral blue B when injected intravenously leaked into the walls of the bronchial vessels down to the region of the small bronchioles (less than or equal to 0.5 mm ID) of acrolein-smoke-exposed dogs but not into the pulmonary vessels. Furthermore, ligation of the bronchial arteries delayed the onset of pulmonary edema (87 +/- 3 min, P less than 0.05) and lessened the magnitude (232 +/- 30 ml, P less than 0.05) at 166 +/- 3 min after acrolein-smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expiratory muscle activity during pulmonary edema in the anesthetized dog.

The present study evaluated the reflex response of the expiratory muscles to pulmonary congestion and edema. The electromyograms of two thoracic and four abdominal expiratory muscles were recorded in 12 anesthetized dogs. Pulmonary edema was induced by rapid saline infusion in six dogs and injection of oleic acid into the pulmonary circulation in the remaining six dogs. Both forms of pulmonary edema reduced pulmonary compliance, interfered with gas exchange, and induced a rapid and shallow breathing pattern. The electrical activity of all abdominal muscles was suppressed during both forms of pulmonary edema. In contrast, the electromyogram activity of the thoracic expiratory muscles was not significantly affected by pulmonary edema. Acute pulmonary arterial hypertension produced in two dogs by inflating a balloon in the left atrium had no effect on ventilation or expiratory muscle electrical activity. In two vagotomized dogs, pulmonary edema did not inhibit the expiratory muscles. We conclude that pulmonary edema suppresses abdominal but not thoracic expiratory muscle activity by vagal reflex pathway(s). Extravasation of fluid into the lung appears to be more important than an increase in pulmonary vascular pressure in eliciting this response.     

Reflex tracheal smooth muscle contraction and bronchial vasodilation evoked by airway cooling in dogs

Pisarri, Thomas E., and Gordon G. Giesbrecht. Reflextracheal smooth muscle contraction and bronchial vasodilation evoked byairway cooling in dogs. J. Appl.Physiol. 82(5): 1566-1572, 1997.Coolingintrathoracic airways by filling the pulmonary circulation with coldblood alters pulmonary mechanoreceptor discharge. To determine whetherthis initiates reflex changes that could contribute to airwayobstruction, we measured changes in tracheal smooth muscle tension andbronchial arterial flow evoked by cooling. In ninechloralose-anesthetized open-chest dogs, the right pulmonary artery wascannulated and perfused; the left lung, ventilated separately, providedgas exchange. With the right lung phasically ventilated, filling theright pulmonary circulation with 5°C blood increased smooth muscletension in an innervated upper tracheal segment by 23 ± 6 (SE) gfrom a baseline of 75 g. Contraction began within 10 s of injection andwas maximal at ~30s. The response was abolished by cervical vagotomy.Bronchial arterial flow increased from 8 ± 1 to 13 ± 2 ml/min, withlittle effect on arterial blood pressure. The time course wassimilar to that of the tracheal response. This response was greatlyattenuated after cervical vagotomy. Blood at 20°C also increasedtracheal smooth muscle tension and bronchial flow, whereas 37°Cblood had little effect. The results suggest that alteration ofairway mechanoreceptor discharge by cooling can initiate reflexes thatcontribute to airway obstruction.

     

Early radiation response of the canine heart and lung

In this study three groups of four adult beagle dogs were irradiated with a 12-Gy single dose to the thorax. The fields used were the entire thorax, the entire thorax with a heart block in place, and the heart with one-third of the lung volume. The response of the lung was evaluated by cellular and biochemical analysis of sequential bronchoalveolar lavage fluids, blood gas analysis, physical examination, and histopathology. Sparing a small volume of lung improved survival. Cardiac function was evaluated by right heart catheterization, echocardiography, physical exam, and histopathology. Pulmonary artery pressure was increased in all dogs, mean systemic artery pressure was decreased in all dogs, and no difference could be shown among the groups. These effects are likely secondary to a reduced pulmonary capillary volume. Stroke volume was significantly deceased in dogs that had their hearts included in the field but not in dogs with their hearts shielded. This effect was not thought to be secondary to lung injury. The influence of lung irradiation on cardiac function was limited to pulmonary hypertension. Pulmonary hypertension may be enhanced by the release of vasoactive compounds. Pulmonary hypertension may contribute to radiation-induced heart failure.     

Direct injury to the bronchial vasculature in anesthetized sheep.

Injury to the bronchial vasculature may contribute to liquid and solute leakage into the lung during noncardiac pulmonary edema. The purpose of this study was to measure changes in hemodynamics, pulmonary mechanics, extravascular lung water, and lung morphometry after selectively injuring the bronchial vasculature in anesthetized sheep. In two groups of seven sheep, we injected oleic acid (0.1 ml/kg) or normal saline directly into the bronchoesophageal artery. We measured systemic and pulmonary arterial pressures, cardiac output, oxygen saturation, pulmonary resistance and compliance, and lung volumes before and 1 and 4 h after injection. The lungs were removed for measurement of extravascular water, histology, and morphometry. Four hours after injection of oleic acid, cardiac output decreased but pulmonary arterial pressure did not change. In addition, pulmonary resistance increased and dynamic compliance and vital capacity decreased. Extravascular lung water was slightly but significantly greater in the oleic acid group. Histological examination showed interstitial edema and leukocytes in airway walls and sloughing of bronchial epithelium but little or no alveolar edema. Morphometric analysis showed significant thickening of airway walls. We conclude that direct injury to the bronchial vasculature increases lung resistance, decreases dynamic compliance, and increases extravascular lung water by the accumulation of an inflammatory infiltrate in airway walls.     

Effect of bronchial artery blood flow on cardiopulmonary bypass-induced lung injury

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37 degrees C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po(2) at a fraction of inspired oxygen of 1.0 (52 +/- 5 vs. 312 +/- 58 mmHg) and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4 mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6 +/- 1 mmHg x l(-1) x min), plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng/ml), extravascular lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (sigma(alb); 0.53 +/- 0.1 vs. 0.82 +/- 0.05). There was a negative correlation (R = 0.95, P < 0.001) between sigma(alb) and the 25-min plasma TNF-alpha concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.     

Respiratory failure after endotoxin infusion in sheep: lung mechanics and lung fluid balance

Infusion of Escherichia coli endotoxin (0.12-1.5 micrograms/kg) into unanesthetized sheep causes transient pulmonary hypertension and several hours of increased lung vascular permeability, after which sheep recover. To produce enough lung injury to result in pulmonary edema with respiratory failure, we infused larger doses of E. coli endotoxin (2.0-5.0 micrograms/kg) into 11 chronically instrumented unanesthetized sheep and continuously measured pulmonary arterial, left atrial and aortic pressures, dynamic lung compliance, lung resistance, and lung lymph flow. We intermittently measured arterial blood gas tensions and pH, made interval chest radiographs, and calculated postmortem extravascular bloodless lung water-to-dry lung weight ratio (EVLW/DLW). Of 11 sheep 8 developed respiratory failure; 7 died spontaneously 6.3 +/- 1.1 h, and one was killed 10 h after endotoxin infusion. All sheep that had a premortem room air alveolar-arterial gradient in partial pressure of O2 (PAo2-Pao2) greater than 42 Torr (58 +/- 5 (SE) Torr) died. Of eight sheep that had radiographs made, six developed radiographically evident interstitial or interstitial and alveolar edema. Pulmonary artery pressure rose from base line 22 +/- 2 to 73 +/- 3 cmH2O and remained elevated above baseline levels until death. There was an initial fourfold decrease in dynamic compliance and sixfold increase in pulmonary resistance; both variables remained abnormal until death. EVLW/DLW increased with increasing survival time after endotoxin infusion, suggesting that pulmonary edema accumulated at the same rate in all fatally injured sheep, regardless of other variables. The best predictor of death was a high PAo2-Pao2. The marked increase in pulmonary resistance and decrease in dynamic compliance occurred too early after endotoxin infusion (15-30 min) to be due to pulmonary edema. The response to high-dose endotoxin in sheep closely resembles acute respiratory failure in humans following gram-negative septicemia. Respiratory failure and death in this model were not due to pulmonary edema alone.     

Bronchial circulation and cyclooxygenase products in acute lung injury

The role of cyclooxygenase products in the response of the bronchial circulation to acute lung injury was examined in 30 dogs. By use of an open-chest preparation the left lower lobe (LLL) pulmonary circulation was isolated, continuously weighed, and perfused in situ. The anastomotic bronchial blood flow [Qbr(s-p)] was measured as the rate of increase in the volume of the LLL-perfusion circuit. Four groups of dogs were studied. In group A, six dogs received cyclooxygenase inhibition (COI) with either indomethacin (2 mg/kg) or ibuprofen (10 mg/kg). In group B (n = 10) lung injury caused by airway instillation of glucose (15 mg) with glucose oxidase (500 micrograms/kg) (G/GO) or LLL pulmonary arterial infusion of alpha-napthyl thiourea (ANTU, 2 mg/kg). Group C (n = 10) received COI, and 30 min later injury was induced as above with either ANTU or G/GO. Group D (n = 4) received COI immediately after anesthesia; then, 30 min after completion of the surgical preparation, injury was induced with ANTU or G/GO. After COI, Qbr(s-p) decreased to 35 +/- 9% of the basal values (P less than 0.05). After administration of ANTU or G/GO, Qbr(s-p) increased irrespective of whether COI was present. 6-Ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2) were measured by radioimmunoassay in the LLL pulmonary artery and systemic venous blood, demonstrating an increase in 6-keto-PGF1 alpha due to surgical preparation and confirming complete COI in those animals receiving COI immediately after anesthesia. These findings demonstrate that 1) the bronchial circulation is capable of a sevenfold increase in flow in response to acute lung injury.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary circulation in embolic pulmonary edema

The ultrasonic method was used in acute experiments on cats with open chest under artificial lung ventilation to obtain blood flow in low-lobar pulmonary artery and vein, the blood pressure in pulmonary artery, as well as the left atrial pressure in fat (olive oil) and mechanical (Lycopodium spores) pulmonary embolism. It is shown that pulmonary embolism produces the decrease in the blood flow in pulmonary artery and vein, the increase of the pressure in pulmonary artery and left atria, the increase of lung vessels resistance. The decrease is observed of systemic arterial pressure, bradycardia, and extrasystole. After 5-10 min the restoration of arterial pressure and heart rhythm occur and partial restoration of blood flow in pulmonary artery and vein. In many experiments the blood flow in vein outdoes that in the artery--it allows to suppose the increase of the blood flow in bronchial artery. After 60-90 min there occur sudden decrease of systemic arterial pressure, the decrease of the blood flow in pulmonary artery and vein. The pressure in pulmonary artery and resistance of pulmonary vessels remain high. Pulmonary edema developed in all animals. The death occurs in 60-100 min after the beginning of embolism.     

Systemic blood flow to sheep lung: comparison of flow probes and microspheres.

Discrepancies exist between experimental measurements of the systemic blood flow to sheep lung by use of microsphere techniques and flow probes on the bronchial artery. In these studies, we simultaneously measured the blood flow through the bronchial artery, using a transit time flow probe, and the systemic blood flow to left lung, using radioactive microspheres. All measurements were made on conscious sheep previously prepared with chronic catheterizations of the left atrium, aorta, and vena cava and a flow probe around the bronchial artery. Inflatable occluder cuffs were placed around the pulmonary and bronchoesophageal arteries. Bronchial artery blood flow in six sheep was 25.3 +/- 5.2 ml/min or 0.4% of the cardiac output. Systemic blood flow to left lung, measured with microspheres, was 54.1 +/- 14.2 ml/min. Calculated systemic blood flow to that portion of sheep lung perfused by the bronchial artery was 127.6 +/- 35.3 ml/min or 1.9% of cardiac output. Occlusion of the bronchoesophageal artery reduced bronchial artery flow to near zero, whereas total systemic blood to the lung was reduced by only 55%. Blood flow to the intraparenchymal cartilaginous airways was reduced 60-90% after occlusion of the bronchoesophageal artery. Sheep, like most mammals, have multiple and complex systemic arterial inputs to the lungs. We conclude that multiple branches of the bronchoesophageal artery provide most but not all of the systemic blood flow to the intraparenchymal cartilaginous airways but that over one-half of the total systemic blood flow to sheep lung comes from sources other than the common bronchial artery.