Modification of bronchial blood flow during allergic airway responses

Ascaris suum antigen effects on mean airflow resistance (RL) and bronchial arterial blood flow (Qbr) were studied in allergic anesthetized sheep with documented airway responses. Qbr was measured with electromagnetic flow probes, and supplemental O2 prevented antigen-induced hypoxemia. Aerosol challenge with this specific antigen increased RL and Qbr significantly. Cromolyn sodium aerosol pretreatment prevented antigen-induced increases in RL but not in Qbr. Intravenous cromolyn, however, prevented increases in Qbr and RL, suggesting a role for mast cell degranulation in both bronchomotor and bronchovascular responses to antigen. Antigen-induced increases in Qbr were not solely attributable to histamine release. Indomethacin pretreatment attenuated the antigen-induced increase in Qbr, thus suggesting that vasodilator cyclooxygenase products contribute to the vascular response. Antigen challenge significantly decreased Qbr after indomethacin and metiamide pretreatment, which suggests that vasoconstrictor substances released after antigen exposure also modulate Qbr; however, released vasodilators overshadow vasoconstrictor effects. Thus antigen challenge affects Qbr by locally releasing histamine and vasodilator prostaglandins as well as vasoconstrictor substances. These effects were independent of antigen-induced changes in systemic and pulmonary hemodynamics.     

Effects of histamine on bronchial artery blood flow and bronchomotor tone

The effects of aerosolized 5% histamine (10 breaths) on bronchial artery blood flow (Qbr), airflow resistance (RL), and pulmonary and systemic hemodynamics were studied in mechanically ventilated sheep anesthetized with pentobarbital sodium. Histamine increased mean Qbr and RL to 252 +/- 45 and 337 +/- 53% of base line, respectively. This effect was significantly different from base line for 30 min after challenge. The histamine-induced increase in RL was blocked by pretreatment with the histamine H1 receptor antagonist, chlorpheniramine, whereas the histamine-induced elevation in Qbr was prevented by the H2 antagonist, metiamide. Both responses were blocked only when both antagonists were present. Changes in Qbr were not directly associated with alterations in systemic and pulmonary hemodynamics or arterial blood gas composition. In vitro histamine caused a dose-dependent contraction of ovine bronchial artery strips that was prevented by H1 antagonist. The H2 agonist, impromidine, caused relaxation of precontracted arterial strips and was more potent and efficacious than histamine, whereas H1 agonists failed to elicit a relaxant response. Thus these findings indicate that histamine aerosol induces a vasodilation in the bronchial vascular bed; histamine has a direct effect on Qbr that is independent of alterations in RL, systemic and pulmonary hemodynamics, or arterial blood gas composition; and, histamine-induced bronchoconstriction is mediated predominantly by H1-receptors, whereas increased Qbr is controlled predominantly by H2-receptors, probably located in resistance vessels. This local effect of histamine on Qbr may have important implications in the pathophysiology of bronchial asthma and pulmonary edema.     

Bronchial circulation in pulmonary artery occlusion and reperfusion

Obstruction of pulmonary arterial blood flow results in minimal biochemical and/or morphological changes in the involved lung. If the lung is reperfused, a syndrome of leukopenia and lung edema occurs. We used the radiolabeled microsphere technique to measure the response of the bronchial circulation in rabbits to acute pulmonary artery occlusion (PAO) and to pulmonary artery reperfusion. We found that the bronchial blood flow (Qbr) decreased from a base line of 0.37 +/- 0.10 to 0.09 +/- 0.04 (SE) ml.min-1.g dry lung-1 (P less than or equal to 0.05) after 4 h of PAO. In a separate group of animals, Qbr 24 h after PAO remained low (0.20 +/- 0.07 ml.min-1.g dry lung-1, P = 0.06). Qbr during PAO was inversely correlated with the wet-to-dry ratio after reperfusion (r = -0.68, P = 0.06). Qbr did not change during 4 h of reperfusion. We speculate that a critical level of Qbr may be necessary during PAO to prevent ischemia/reperfusion injury from occurring.     

Measurement of bronchial arterial blood flow and bronchovascular resistance in sheep

We studied the bronchial arterial blood flow (Qbr) and bronchial vascular resistance (BVR) in sheep prepared with carotid-bronchial artery shunt. Nine adult sheep were anesthetized, and through a left thoracotomy a heparinized Teflon-tipped Silastic catheter was introduced into the bronchial artery. The other end of the catheter was brought out through the chest wall and through a neck incision was introduced into the carotid artery. A reservoir filled with warm heparinized blood was connected to this shunt. The height of blood column in the reservoir was kept constant at 150 cm by adding more blood. Qbr was measured, after interrupting the carotid-bronchial artery flow, by the changes in the reservoir volume. The bronchial arterial back pressure (Pbr) was measured through the shunt when both carotid-bronchial artery and reservoir Qbr had been temporarily interrupted. The mean Qbr was 34.1 +/- 2.9 (SE) ml/min, Pbr = 17.5 +/- 3.3 cmH2O, BVR = 3.9 +/- 0.5 cmH2O X ml-1 X min, mean pulmonary arterial pressure = 21.5 +/- 3.6 cmH2O, and pulmonary capillary wedge pressure (Ppcw) = 14.3 +/- 3.7 cmH2O. We further studied the effect of increased left atrial pressure on these parameters by inflating a balloon in the left atrium. The left atrial balloon inflation increased Ppcw to 25.3 +/- 3.1 cmH2O, Qbr decreased to 21.8 +/- 2.4 ml/min (P less than 0.05), and BVR increased to 5.5 +/- 1.0 cmH2O.ml-1.min (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

Effects of lung inflation on pulmonary arterial blood volume in intact dogs.

The isolated effects of alterations of lung inflation and transmural pulmonary arterial pressure (pressure difference between intravascular and pleural pressure) on pulmonary arterial blood volume (Vpa) were investigated in anesthetized intact dogs. Using transvenous phrenic nerve stimulation, changes in transmural pulmonary arterial pressure (Ptm) at a fixed transpulmonary pressure (Ptp) were produced by the Mueller maneuver, and increases in Ptp at relatively constant Ptm by a quasi-Valsalva maneuver. Also, both Ptm and Ptp were allowed to change during open airway lung inflation. Vpa was determined during these three maneuvers by multiplying pulmonary blood flow by pulmonary arterial mean transit time obtained by an ether plethysmographic method. During open airway lung inflation, mean (plus or minus SD) Ptp increased by 7.2 (plus or minus 3.7) cmH2O and Ptm by 4.3 (plus or minus 3.4) cmH2O for a mean increase in Vpa by 26.2 (plus or minus 10.7) ml. A pulmonary arterial compliance term (Delta Vpa/Delta Ptm) calculated from the Mueller maneuver was 3.9 ml/cmH2O and an interdependence term (Delta Vpa/Delta Ptp) calculated from the quasi-Valsalva maneuver was 2.5 ml/cmH2O for a 19% increase in lung volume, and 1.2 ml/cmH2O for an increase in lung volume from 19% to 35%. These findings indicate that in normal anesthetized dogs near FRC for a given change in Ptp and Ptm the latter results in a greater increase of Vpa.     

Effect of lung volume on plateau response of airways and tissue to methacholine in dogs.

We have recently shown in dogs that much of the increase in lung resistance (RL) after induced constriction can be attributed to increases in tissue resistance, the pressure drop in phase with flow across the lung tissues (Rti). Rti is dependent on lung volume (VL) even after induced constriction. As maximal responses in RL to constrictor agonists can also be affected by changes in VL, we questioned whether changes in the plateau response with VL could be attributed in part to changes in the resistive properties of lung tissues. We studied the effect of changes in VL on RL, Rti, airway resistance (Raw), and lung elastance (EL) during maximal methacholine (MCh)-induced constriction in 8 anesthetized, paralyzed, open-chest mongrel dogs. We measured tracheal flow and pressure (Ptr) and alveolar pressure (PA), the latter using alveolar capsules, during tidal ventilation [positive end-expiratory pressure (PEEP) = 5.0 cmH2O, tidal volume = 15 ml/kg, frequency = 0.3 Hz]. Measurements were recorded at baseline and after the aerosolization of increasing concentrations of MCh until a clear plateau response had been achieved. VL was then altered by changing PEEP to 2.5, 7.5, and 10 cmH2O. RL changed only when PEEP was altered from 5 to 10 cmH2O (P < 0.01). EL changed when PEEP was changed from 5 to 7.5 and 5 to 10 cmH2O (P < 0.05). Rti and Raw varied significantly with all three maneuvers (P < 0.05). Our data demonstrate that the effects of VL on the plateau response reflect a complex combination of changes in tissue resistance, airway caliber, and lung recoil.     

Effects of continuous positive airway pressure breathing on lung volume and distensibility

In this study the effects on lung elastic behavior of 10 min of breathing at a continuous positive airway pressure (CPAP) of 10 cmH2O were examined in 10 normal subjects. To investigate whether any changes were induced by release of prostaglandins, the subjects were also pretreated with the cyclooxygenase inhibitor indomethacin. CPAP produced a significant (P less than 0.001) upward shift of the pressure-volume (PV) curve [change in total lung capacity (delta TLC) 374 +/- 67 (SE) ml, mean delta volume at a transpulmonary pressure of 15 cmH2O (delta VL15) 279 +/- 31 ml] with no change in K, an index of lung distensibility. After CPAP the PV curves returned to normal base line within 20 min. The same pattern was observed after indomethacin, but the increase in TLC was significantly less (P less than 0.01) (mean delta TLC 206 +/- 42 ml) mainly because of a slight and not statistically significant increase in base-line TLC. In five subjects further PV curves with and without CPAP were obtained greater than or equal to 7 days after indomethacin. The responses were not significantly different from those obtained before indomethacin (mean delta TLC 366 +/- 89, mean delta VL15 296 +/- 42 ml). We conclude that CPAP produces an upward shift of the PV curve without a change in lung distensibility. In addition, there may be a small degree of resting alveolar duct tone that is influenced by indomethacin.     

Relationship of end-expiratory pressure, lung volume, and 99mTc-DTPA clearance

We investigated the dose-response effect of positive end-expiratory pressure (PEEP) and increased lung volume on the pulmonary clearance rate of aerosolized technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA). Clearance of lung radioactivity was expressed as percent decrease per minute. Base-line clearance was measured while anesthetized sheep (n = 20) were ventilated with 0 cmH2O end-expiratory pressure. Clearance was remeasured during ventilation at 2.5, 5, 10, 15, or 20 cmH2O PEEP. Further studies showed stepwise increases in functional residual capacity (FRC) (P less than 0.05) measured at 0, 2.5, 5, 10, 15, and 20 cmH2O PEEP. At 2.5 cmH2O PEEP, the clearance rate was not different from that at base line (P less than 0.05), although FRC was increased from base line. Clearance rate increased progressively with increasing PEEP at 5, 10, and 15 cmH2O (P less than 0.05). Between 15 and 20 cmH2O PEEP, clearance rate was again unchanged, despite an increase in FRC. The pulmonary clearance of aerosolized 99mTc-DTPA shows a sigmoidal response to increasing FRC and PEEP, having both threshold and maximal effects. This relationship is most consistent with the hypothesis that alveolar epithelial permeability is increased by lung inflation.     

Partitioning of pulmonary resistance in calves

Nine right apical lobes of healthy Friesian calves and 10 right apical lobes of double-muscled calves of Belgian White and Blue (BWB) breed were suspended in an airtight box, inflated at a constant transpulmonary pressure (Ptp), and subjected to quasi-sinusoidal pressure changes (amplitude: 0.5 kPa) at a frequency of 30 cycles/min. Lobar resistance (RL) was partitioned at six different lung volumes into three components: central airway resistance (Rc), small airway resistance (Rp), and tissue resistance (Rt). Pressure in small airways (2-3 mm ID) was measured with a retrograde catheter. Alveolar pressure was sampled in capsules glued onto the punctured pleural surface. RL was minimal at values of Ptp comprised between 0.5 and 0.7 kPa and increased at higher and lower values of Ptp. At a Ptp of 0.5 kPa, Rc, Rp, and Rt represented 30, 15, and 55% of RL, respectively, in Friesian calves and 25, 25, and 50% in BWB calves. Rp increased markedly at low lung volumes. Rt was responsible for the increase of RL at high Ptp. Rc tended to decrease at high Ptp. The significantly higher values of Rp in BWB calves (P less than 0.05) might explain the sensitivity of this breed to severe bronchopneumonia.     

Acute increase in anastomotic bronchial blood flow after pulmonary arterial obstruction

We examined the acute changes in anastomotic bronchial blood flow (Qbr) serially for the 1st h after pulmonary arterial obstruction and subsequent reperfusion. We isolated and perfused the pulmonary circulation of the otherwise intact left lower lobe (LLL) with autologous blood in the widely opened chest of anesthetized dogs. Qbr was measured from the amount of blood overflowing from the closed pulmonary vascular circuit and the changes in the lobe weight. The right lung and the test lobe (LLL) were ventilated independently. The LLL, which was in zone 2 (mean pulmonary arterial pressure = 14.8 cm H2O, pulmonary venous pressure = 0, alveolar pressure = 5-15 cmH2O), was weighed continuously. The systemic blood pressure, gases, and acid-base status were kept constant. In control dogs without pulmonary arterial obstruction, the Qbr did not change for 2 h. Five minutes after pulmonary arterial obstruction, there was already a marked increase in Qbr, which then continued to increase for 1 h. After reperfusion, Qbr decreased. The increase in Qbr was greater after complete lobar than sublobar pulmonary arterial obstruction. It was unaltered when the downstream pulmonary venous pressure was increased to match the preobstruction pulmonary microvascular pressure. Thus, in zone 2, reduction in downstream pressure was not responsible for the increase in Qbr; neither was the decrease in alveolar PCO2, since ventilating the lobe with 10% CO2 instead of air did not change the Qbr. These findings suggest that there is an acute increase in Qbr after pulmonary arterial obstruction and that is not due to downstream pressure or local PCO2 changes.     

Role of vagal C-fiber afferents in the bronchomotor response to lactic acid in the newborn dog.

We addressed the hypothesis that vagal C-fiber afferents and cyclooxygenase products are the mechanisms responsible for lactic acid (LA)-induced bronchoconstriction in the newborn dog. Perineural capsaicin and indomethacin were used to block conduction of vagal C fibers and production of cyclooxygenase products, respectively. Perineural capsaicin eliminated (85%) the increase in lung resistance (RL; 45 +/- 5.6%) due to capsaicin (25 microg/kg), whereas the increase in RL (54 +/- 6.9%) due to LA (0.4 mmol/kg) was only inhibited by 37 +/- 4.7% (P < 0.05). Atropine reduced LA-induced bronchoconstriction (42 +/- 2.1%) by an amount similar to that obtained with perineural capsaicin. However, inhibition was significantly increased when atropine was combined with indomethacin (61 +/- 2.7%; P < 0.05), implicating cyclooxygenase products in the LA-induced bronchoconstrictor response. We conclude that the mechanisms responsible for LA-induced bronchoconstriction in the newborn are 1) activation of vagal C-fibers, which, through projections to medullary respiratory centers, leads to activation of vagal cholinergic efferents; 2) production of cyclooxygenase products, which cause bronchoconstriction independent of medullary involvement; and 3) an unknown bronchoconstrictor mechanism, putatively tachykinin mediated. On the basis of our data, pharmaceutical targeting of pulmonary afferents would prevent multiple downstream mechanisms that lead to airway narrowing due to inflammatory lung disease.     

Large-volume ventilation results in bronchoconstriction of Basenji-Greyhound dogs

We compared the effects of large-volume ventilation on airway responses to aerosolized histamine in anesthetized mongrel dogs with its effects in Basenji-Greyhound crossbred (B-G) dogs. Before bronchoconstriction, large inflations resulted in only small changes of dynamic compliance (Cdyn) and pulmonary resistance (RL) in both groups of dogs. After the induction of a moderate degree of bronchoconstriction with aerosolized histamine, large inflations had a more substantial effect; Cdyn increased by 7.5 +/- 2.3% (mean +/- SE; P less than 0.05), and RL decreased by 32 +/- 3.4% (P less than 0.001) in the mongrel dogs. In the B-G group, Cdyn increased by only 0.2 +/- 1.8% (NS), and RL increased by 29.3 +/- 9.2% (P less than 0.05); these changes differed significantly (P less than 0.05) from those observed in the mongrel dogs. Large-volume ventilation following the administration of indomethacin (10 mg/kg iv) and histamine increased Cdyn by 11.4 +/- 1.8% (NS vs. without indomethacin) and decreased RL by 43.9 +/- 3.4% (P less than 0.05) in the mongrel group. In the B-G group large-volume ventilation increased Cdyn by 7.6 +/- 1.7% (P less than 0.01) and decreased RL by 15.7 +/- 8.1% (P less than 0.05). Thus indomethacin enhanced the bronchodilator effects of large-volume ventilation in mongrel dogs and reversed the bronchoconstrictor effect of this maneuver on RL in B-G dogs.     

Inhaled porcine pancreatic elastase causes bronchoconstriction via a bradykinin-mediated mechanism.

Neutrophil elastase has been linked to inflammatory lung diseases such as chronic obstructive pulmonary disease, adult respiratory distress syndrome, emphysema, and cystic fibrosis. In guinea pigs, aerosol challenge with human neutrophil elastase causes bronchoconstriction, but the mechanism by which this occurs is not completely understood. Our laboratory previously showed that human neutrophil elastase releases tissue kallikrein (TK) from cultured tracheal gland cells. TK has been identified as the major kininogenase of the airway and cleaves both high- and low-molecular weight kininogen to yield lysyl-bradykinin. Because inhaled bradykinin causes bronchoconstriction and airway hyperresponsiveness in asthmatic patients and allergic sheep, we hypothesized that elastase-induced bronchoconstriction could be mediated by bradykinin. To test this hypothesis, we measured lung resistance (RL) in sheep before and after inhalation of porcine pancreatic elastase (PPE) alone and after pretreatment with a bradykinin B(2) antagonist (NPC-567), the specific human elastase inhibitor ICI 200,355, the histamine H(1)-antagonist diphenhydramine hydrochloride, the cysteinyl leukotriene 1 receptor antagonist montelukast, or the cyclooxygenase inhibitor indomethacin. Inhaled PPE (125-1,000 microg) caused a dose-dependent increase in RL. Aerosol challenge with a single 500 microg dose of PPE increased RL by 132 +/- 8% over baseline. This response was blocked by pretreatment with NPC-567 and ICI-200,355 (n = 6; P < 0.001), whereas treatment with diphenhydramine hydrochloride, montelukast, or indomethacin failed to block the PPE-induced bronchoconstriction. Consistent with pharmacological data, TK activity in bronchial lavage fluid increased 134 +/- 57% over baseline (n = 5; P < 0.02). We conclude that, in sheep, PPE-induced bronchoconstriction is in part mediated by the generation of bradykinin. Our findings suggest that elastase-kinin interactions may contribute to changes in bronchial tone during inflammatory diseases of the airways.     

Response of slowly adapting pulmonary stretch receptors to reduced lung compliance

We examined the steady-state response of slowly adapting pulmonary stretch receptors (SAPSRs) to reduced lung compliance in open-chest cats with lungs ventilated at eupneic rate and tidal volume (VT) and with a positive end-expiratory pressure (PEEP) of 3-4 cmH2O. Transient removal of PEEP decreased compliance by approximately 30% and increased transpulmonary pressure (Ptp) by 1-2.5 cmH2O. Reduction of compliance significantly decreased SAPSR discharge in deflation and caused a small increase in discharge at the peak of inflation; it had little effect on discharge averaged over the ventilatory cycle. Increasing VT to produce a comparable increase in Ptp significantly increased peak discharge. Thus unlike rapidly adapting receptors, whose discharge is increased more effectively by reduced compliance than by increased VT, SAPSRs are stimulated by increased VT but not by reduced compliance. We speculate that the most consistent effect of reduced compliance on SAPSRs (the decrease in deflation discharge) was due to the decreased time constant for deflation in the stiffer lung. This alteration in firing may contribute to the tachypnea evoked as the lungs become stiffer.     

Temperature alters bronchial blood flow response to pulmonary arterial obstruction

Lobar bronchial blood flow has been reported to increase and decrease acutely after pulmonary arterial obstruction (PAO). Because bronchial blood flow (Qbr) to the trachea and bronchi is influenced by inspired air temperature, we investigated whether temperature differences could explain these disparate results. In 10 open-chested dogs the left lower lobe (LLL) was isolated and perfused in situ with autologous blood at a controlled temperature with an independent vascular circuit. The abdomen and the chest of the dog were enclosed in a Plexiglas box in which air was fully humidified and temperature could be regulated. Qbr, determined by the reference flow technique using 16 micron microspheres, was measured before and 30 min after onset of PAO with the air in the box being either at 27 or 39 degrees C and with warmed LLL blood (37 degrees C) in the latter condition. Anastomotic bronchial blood flow [Qbr(s-p), determined as overflow from the closed LLL vascular circuit and measured in ml X min-1 X 100 g dry lung wt-1 X 100 Torr mean systemic pressure-1] was measured continuously at both temperatures. Both before and after PAO, Qbr and Qbr(s-p) were closely correlated: Qbr (ml/min) = 1.12 + 0.978Qbr(s-p); R = 0.912. This was true regardless of the presence or the absence of pulmonary flow, showing that the distribution of bronchial blood flow between the anastomotic and the nonanastomotic portion does not change acutely during PAO. When the air in the box was 27 degrees C, Qbr(s-p) was 19.5 +/- 5.2 (SE) and increased to 38.6 +/- 8.1 with PAO (P less than 0.007).(ABSTRACT TRUNCATED AT 250 WORDS)     

Late-phase bronchial vascular responses in allergic sheep

Sheep were classified on the basis of their airway response to Ascaris suum antigen aerosols as allergic or nonsensitive. Allergic sheep were classed as acute or dual responders. Acute responders had only an immediate increase in mean airflow resistance after antigen, whereas dual responders had an immediate and late-phase (6-8 h after antigen challenge) increase in mean airflow resistance; nonsensitive sheep had minimal airway responses to antigen (less than 30% increase from base line). The sheep were anesthetized 2 wk later and, after a left thoracotomy, were challenged with antigen to determine bronchial vascular responses; bronchial artery blood flow was measured with an electromagnetic flow probe. Airway responses to antigen aerosol challenge were similar in the anesthetized and conscious animals. The mean fall in bronchial vascular resistance (BVR) immediately after antigen challenge was similar in acute and dual responders (41 +/- 7 and 47 +/- 9% of base line, respectively). In dual responders, late-phase airway responses were preceded by a significant increase from base line in Qbr and a fall in bronchovascular resistance (BVR). The mean fall in BVR 6-8 h after antigen challenge in documented dual responders was significantly different from bronchial vascular responses in acute responders (59 +/- 3 vs. 89 +/- 10%, respectively). Sheep without airway responses to A. suum had no significant changes in bronchial hemodynamics or airways mechanics. Late-phase-associated changes in BVR are a specific response to antigen challenge and may be a sensitive index of mediators being released.(ABSTRACT TRUNCATED AT 250 WORDS)     

Response of the bronchial circulation to acute hypoxemia and hypercarbia in the dog

We have examined the effect of acute hypoxemia and hypercarbia on bronchial blood flow (Qbr) in 10 anesthetized, ventilated, open-chest dogs using a modification of the radioactive microsphere technique. After surgery, dogs were divided into two groups of five. Group 1 was ventilated for 30 min with each of the following gas mixtures: 1) room air; 2) 15% O2-85% N2; 3) 10% O2-90% N2, and group 2 with 1) room air; 2) 5% CO2-30% O2-65% N2; 3) 10% CO2-30% O2-60% N2. Measurements of pulmonary arterial, left atrial and aortic pressures, cardiac output, and blood gases were made before injection of 46Sc-, 153Gd-, and 103Ru-labeled microspheres into the left atrium as a marker of Qbr. After the final measurements, dogs were killed and the lungs removed and the parenchyma stripped off the large and small airways of the left lung. Knowing the radioactivity in the trachea, bronchi, parenchyma, and in the blood from the reference-flow sample and also the aortic and left atrial pressures, total and regional Qbr, and bronchovascular resistance (BVR) were calculated. Results showed that acute hypoxemia (10% O2) caused a significant (P less than 0.05) decrease in Qbr and increase in BVR and acute hypercarbia (10% CO2) caused a significant (P less than 0.05) increase in Qbr and decrease in BVR.     

Airway responsiveness to inhaled and intravenous carbachol in sheep: effect of airway mucus

Excessive airway mucus can alter both the mass and site of aerosol deposition, which, in turn, may affect airway responsiveness to inhaled materials. In six prone sheep, we therefore measured pulmonary airflow resistance (RL) and cumulative aerosol deposition during five standard breaths (AD5) at base line and 3 min after inhalation challenge with 2% carbachol in buffered saline (10 breaths, tidal volume = 500 ml) or after an intravenous loading dose of carbachol (3 micrograms/kg) followed by a constant infusion of 0.3 micrograms.kg-1.min-1 with and without instillation of 20 ml of a mucus simulant (MS) into the distal end of each of the main bronchi or 30 ml of MS into the right main bronchus only by means of a flexible fiber-optic bronchoscope. Before carbachol challenge, RL did not change with MS into either both lungs or one lung only. AD5 increased from 36 +/- 2% (SE) before to 42 +/- 2% after MS instillation into both lungs (P less than 0.05) but remained unchanged after MS into one lung. After carbachol inhalation, RL increased significantly by 154 +/- 20 before and 126 +/- 25% after MS into both lungs and 162 +/- 24 before and 178 +/- 31% after MS into one lung (P less than 0.05). When the percent increase in RL was normalized for total aerosol deposition (% delta RL/AD5), the normalized values were lower after MS (3.0 +/- 0.5) than before MS (4.4 +/- 0.3) into both lungs (P less than 0.05) but were not significantly different before and after MS into the right lung only.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of increase in anastomotic blood flow following pulmonary arterial occlusion

We have previously shown that there is an acute increase in anastomotic bronchial blood flow (Qbr) after pulmonary arterial obstruction in dogs. We examined the role of arachidonic acid metabolites in mediating this increase. The left lower lobe (LLL) was isolated and perfused (zone 2) with autologous blood in open-chested anesthetized dogs (n = 19). Qbr was measured from the amount of blood that overflowed from the closed vascular circuit of the suspended LLL and changes in its weight. In the control animals, there was a prompt and significant increase in Qbr following pulmonary arterial obstruction. Pretreatment with indomethacin (n = 6) or sodium salicylate (n = 4) almost completely blocked this rise in Qbr. Following pulmonary arterial occlusion, there was a rise in both thromboxane and a prostacyclin metabolite (6-keto-PGF1 alpha) in the blood of the pulmonary circulation of the LLL, although the 6-keto-PGF1 alpha rose relatively more. Pretreatment with indomethacin caused a fall in both thromboxane and prostacyclin levels (n = 3), which no longer rose after pulmonary arterial occlusion. These findings suggested that the balance of the vasodilator (prostacyclin) and vasoconstrictor (thromboxane) prostaglandins may play an important role in mediating the rise in Qbr that follows pulmonary arterial obstruction.