Bronchial Blood Flow Research Articles

Bronchial Arterial Devascularization. An Experimental Study in Pigs

Objective - The lungs have dual blood supply: The bronchial and the pulmonary circulation. The importance of bronchial circulation is disputed. The purpose of this study was to establish an experimental model to examine the importance of the bronchial artery. Design - Comparative porcine experimental study. The surgical technique was evaluated in group A (n = 9). Group B (n = 8) underwent left bronchial arterial devascularization. In group C (n = 9) the left principal bronchus was devascularized, transsected, and reanastomosed. In groups B and C bronchial mucosal blood flow was studied with laser-Doppler velocimetry. Devascularization was controlled by angiography at section, and specimens were examined with conventional histology and scanning electron microscopy. The right bronchus served as control. Results - In group B devascularization caused considerable, yet insignificant reduction in bronchial mucosal blood flow index (p = 0.1282) postoperatively, and after 1 week (p = 0.0678), insignificant histologic (p > 0.2) changes, and no scanning electron microscopy differences. In group C devascularization with bronchial transsection caused significant reduction in mucosal blood flow index (p = 0.0277) postoperatively and after 1 week (p = 0.0277), significant histologic changes (p = 0.0277), and insignificant (p = 0.069) changes in scanning electron microscopy. Conclusion - Bronchial arterial devascularization with transsection caused significant physiologic and morphologic changes, and a model with bronchial devascularization should include transsection.

Bronchovascular Role In Pulmonary Congestion

1. A postulated role for the bronchial circulation in the development of pulmonary congestion may be based on recent studies of bronchovascular control. 2. The bronchial circulation is the nutrient blood supply of the conducting airways and, therefore, plays an important role in the function of the bronchial mucosa. Mucosal swelling secondary to elevation of mucosal capillary hydrostatic pressure may decrease airway calibre, increase resistance to airflow and precipitate symptoms of pulmonary congestion. 3. Resting mucosal capillary hydrostatic pressure is relatively constant due to autoregulation of bronchial blood flow and is maintained low by nett bronchovascular constriction due to the dominance of autonomic vasoconstriction over nitric oxidedependent vasodilatation. 4. Bronchial blood flow is also regulated by cardiac afferent reflexes. Stimulation of cardiac vagal and spinal afferents produces vasodilatation and vasoconstriction, respectively. Tonic activity of cardiac spinal afferents probably contributes to the resting autonomic vasoconstriction. 5. Therefore, mild heart failure, which is associated with abnormal cardiovascular reflex function, may decrease cardiac spinal afferent-mediated bronchial vasoconstriction and produce active dilatation due to stimulation of cardiac vagal afferents by excessive myocardial stretch, leading to bronchial mucosal swelling and pulmonary congestion.

Differential effects of furosemide on porcine bronchial arterial and airway smooth muscle

Furosemide attenuates airway obstruction in asthmatic subjects when administered as an aerosol pretreatment. This protective effect of furosemide could be related to relaxation of bronchial smooth muscle or to increased bronchial blood flow. To determine whether furosemide dilates bronchial smooth muscle, isometric contractile responses in distal bronchi from young pigs were studied. In bronchial smooth muscle rings that were precontracted with 10(-5) M acetylcholine, significant relaxation occurred with 10(-8) to 3 x 10(-6) M isoproterenol but not with 10(-8) to 10(-3) M furosemide. In contrast, bronchial arteries that were precontracted with either 10(-4) M norepinephrine or 10(-8) M vasopressin significantly relaxed in response to 10(-4) to 3 x 10(-3) M and 10(-3) to 3 x 10(-3) M furosemide, respectively. We conclude that furosemide, under the described experimental conditions, relaxes airway vascular smooth muscle but not bronchial smooth muscle. These results are consistent with previous suggestions that inhaled furosemide increases blood flow to airway tissues (Gilbert IA, Lenner KA, Nelson JA, Wolin AD, and Fouke JM. J Appl Physiol 76: 409-415, 1994).

Effects of preoperative chemotherapy and radiation therapy on human bronchial blood flow

Objective: We investigated the relationship between bronchial mucosal blood flow around the area of lung resection and the state of healing of the bronchial stump in patients after chemotherapy with or without radiation therapy. Methods: Ninety patients with primary lung cancer were divided into the following 3 groups: group A, 72 patients who had no preoperative therapy; group B, 10 patients who had chemotherapy; and group C, 8 patients who had chemoradiation (60 Gy) therapy. Bronchial mucosal blood flow was measured preoperatively, intraoperatively, and postoperatively (days 8-10) with a laser Doppler flowmeter. Results: In groups A and B bronchial mucosal blood flow was preserved sufficiently around the surgical site, and the healing of the bronchial stump was satisfactory. On the contrary, preoperative blood flow in group C was 70% of the preoperative value in group A and decreased further intraoperatively. Healing of the bronchial stump was poor, and a bronchopleural fistula occurred in one patient of group C. Conclusion: Preoperative chemoradiation therapy may adversely affect bronchial mucosal blood flow and healing of the bronchial stump, although lymphadenectomy and preoperative chemotherapy had little effect. It is recommended that the bronchial stump should be covered with pedicled viable tissue after chemoradiation therapy for prophylaxis against bronchial complications. (J Thorac Cardiovasc Surg 2000;119:939-45)

Bronchial vasodilation evoked by increased lower airway osmolarity in dogs.

Hyperosmotic saline solutions stimulate lower airway sensory nerves. To determine whether airway hyperosmolarity evokes neurally mediated changes in bronchial artery blood flow (Qbr), we measured the effect of injection of small volumes (1 ml) of hyperosmotic saline into a right lobar bronchus on Qbr of anesthetized, artificially ventilated dogs. In 14 dogs, hyperosmotic saline (1,200 and 2,400 mmol/l) increased Qbr by 58 +/- 12 (SE) and 118 +/- 12%, respectively, from a baseline of 8 +/- 2 ml/min. Qbr increased within 6-8 s of the injections, peaked at 20 s, and returned to control over 2-3 min. Isosmotic saline had minimal effects. In contrast, hyperosmotic saline decreased flow in an intercostal artery that did not supply the airways. The bronchial vasodilation was decreased by 72 +/- 11% after combined blockade of alpha-adrenoceptors and muscarinic cholinergic receptors and by 66 +/- 6% when the cervical vagus nerves were cooled to 0 degrees C. Blockade of H(1) and H(2) histamine receptors did not reduce the nonvagal response. We conclude that hyperosmolarity of the lower airways evokes bronchial vasodilation by both a centrally mediated reflex that includes cholinergic and adrenergic efferent pathways and by unidentified local mechanisms.

Pulmonary and bronchial circulatory responses to segmental lung injury.

In regional lung injury, pulmonary blood flow decreases to the injured regions, and anastomotic bronchial blood flow and total bronchial blood flow increase. However, the pattern of redistribution of the two blood flows to the injured and noninjured areas is not known. In six anesthetized sheep, pulmonary and bronchial blood flows were measured with 15-microm fluorescent microspheres by using the reference flow method. Blood flows were measured in the control state and 1 h after instilling 1 ml/kg of 0. 1 N hydrochloric acid into a dependent segment of the left lung. The lungs were then removed, dried, and cubed into approximately 2-cm cubes while spatial coordinates were noted. Blood flow to each piece was calculated. Mean pulmonary blood flow to the noninjured pieces went from 730 +/- 246 to 574 +/- 347 ml/min (P = 0.22), whereas in the injured pieces the pulmonary blood flow decreased from 246 +/- 143 to 56 +/- 46 ml/min (P < 0.01). In contrast, bronchial blood flow to the injured pieces increased from 0.51 +/- 0.1 to 1.43 +/- 0. 85 ml/min (P = 0.005). We measured the change in flow as it related to the distance from the center of the injured area. Pulmonary blood flow decreased most at the center of the injury, whereas bronchial blood flow doubled at the center of injury and decreased with the distance away from the injury. The absolute increase in bronchial blood flow was substantially less than the decrease in pulmonary blood flow in the injured pieces. We also partitioned the observed variation in pulmonary and bronchial blood flow into that attributable to structure and that due to lung injury and found that 48% of the variation in pulmonary blood flow could be attributed to structure, whereas in the bronchial circulation 70% was attributable to structure. The reasons for these differences are not known and may reflect the intrinsic properties of the systemic and pulmonary circulations.

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.

Time course and pattern of pulmonary flow distribution following unilateral airway occlusion in sheep.

1. Unilateral bronchial occlusion causes ipsilateral hypoxic pulmonary vasoconstriction, which shifts blood flow towards the other lung. We studied the time course of flow diversion following acute bronchial occlusion, and the temporal effect of the latter on blood gases and vertical distribution of blood flow within the two lungs. 2. Serial infusion of radioactive or fluorescent microspheres were given to each of seven adult standing sheep before, during occlusion of the left mainstem bronchus for up to 6 min, and after release of occlusion. Pulmonary and systemic arterial pressures were recorded continuously and arterial and mixed venous blood gases were determined intermittently. Post-mortem, the lungs were inflated, dried and cut into slices. Relative blood flow at the time of infusion was expressed as the weight-normalized intensity of each tracer in each slice or lung divided by the weight-normalized intensity in the two lungs. 3. Within 30 s, 1 min and 2 min after onset of occlusion, flow in the occluded lung had decreased to 68-84% (range), 51-78% and 43-79% respectively, of the initial value. In the contralateral lung, flow increased by 10-24%, 14-37% and 23-39% respectively. The distribution of flow along the gravitational axis within each lung varied widely between animals, both before and during occlusion. The during-occlusion profiles in the occluded lung differed from those in the non-occluded lung. In either lung, during-occlusion profiles could not be predicted with certainty from the pre-occlusion profiles. Two minutes post-occlusion, inter- and intra-lung flow distribution were nearly the same as before occlusion. Arterial oxygen tension fell in the first minute of occlusion, but never below 7.5 kPa, and increased slowly thereafter. Arterial carbon dioxide tension increased slightly throughout the occlusion period. No appreciable changes in systemic or pulmonary artery pressure were observed. Post-occlusion, arterial oxygen tension was still sub-normal, while carbon dioxide tension continued to increase. 4. We conclude that acute unilateral bronchial occlusion diverts blood flow within 30 s towards the contralateral lung. This rapidly occurring flow diversion prevents the development of severe arterial hypoxaemia. The variable and largely unpredictable distribution of blood flow in the hyperfused non-occluded lung might explain some of the gas-exchange abnormalities observed in physiologically hyperfused lungs and in patients with one hyperfused lung.

Effect of reduced bronchial circulation on lung fluid flux after smoke inhalation in sheep.

We determined the effect of reduced bronchial blood flow on lung fluid flux through changes in lung lymph flow, lung wet weight-to-dry weight (wet/dry) ratios, and pulmonary microvascular reflection coefficient (sigma). In the first of two surgical procedures, Merino ewes (n = 21) were surgically prepared for chronic study. Five to seven days later, in a second operation, the bronchial artery of the injection group (n = 7) was ligated, and 4 ml of 70% ethanol were injected into the bronchial artery to cause sclerosis of the airway circulation. In the ligation group (n = 7), only the bronchial artery was ligated. In the sham group (n = 7), the bronchial artery was surgically exposed but left intact without ligation or ethanol injection. One day after these operations the animals received a tracheotomy and 48 breaths of cotton smoke. The value of sigma was determined at two points: 24 h before the second surgical procedure and 24 h after smoke inhalation. Lung lymph flow, blood-gas parameters, and hemodynamic data were measured every 4 h after injury. At the end of investigation, samples of lung were taken for determination of blood-free wet/dry ratio. In the sham group, inhalation injury induced a gradual increase in pulmonary vascular resistance and lung lymph flow, which was associated with deterioration of oxygenation. Reduction of the bronchial blood flow attenuated these pathophysiological changes, and the degree of this attenuation was greater in the injection group than in the ligation group. The value of sigma was significantly higher after smoke inhalation in the injection group compared with the sham group (0.77 +/- 0.04 vs. 0.61 +/- 0.03, means +/- SE) at 24 h. The mean wet/dry ratio value of the injection group animals was 30% less than that of the sham group. Our data show that the bronchial circulation contributes to edema formation in the lung occurring after acute lung injury with smoke inhalation.

This Month in the Journal

This Month in the Journal

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.

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.

Autonomic control of bronchial circulation in awake sheep during rest and behaviour.

1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bronchovascular dilatation induced by non-adrenergic, non-cholinergic (NANC) mechanisms observed in the dog exist in sheep. 2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prior thoracotomy. 3. Cumulative and factorial analysis of responses to randomized combinations of autonomic alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%. 4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separate alpha- and beta-adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator alpha-/beta-adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep. 5. Nitric oxide (NO) synthase inhibition in sheep using NG-nitro-L-arginine following blockade of alpha- and beta-adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects. 6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C-fibre axon reflex using substance P, calcitonin gene-related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects.

Inhalation injury increases the anastomotic bronchial blood flow in the pouch model of the left ovine lung.

Pulmonary parenchymal damage often occurs after airway injury. Bronchial venous drainage empties into the pulmonary microvasculature. We developed an in vivo model to study the bronchopulmonary portal system after smoke inhalation injury. Eight ewes were instrumented with hydraulic occluders on the left pulmonary artery (LPA), the left pulmonary vein, and the bronchoesophageal artery (BEA); a catheter in the LPA; and Swan-Ganz and femoral artery catheters. The vasculature between the occluders was defined as pouch. At stable mean arterial and right pulmonary arterial pressures, LPA occlusion reduced the left pulmonary artery pressure (LPAP) from 17 +/- 1 mmHg to 8 +/- 1 mmHg (p < .05). After left pulmonary vein occlusion, LPAP rose to 28 +/- 4 mmHg (p < .05 vs. baseline), indicating that systemic blood had entered the pouch. Opening the pouch to atmospheric pressure revealed an anastomotic bronchial blood flow (anastomotic Qbr) of .76 +/- .11% of cardiac output (CO). BEA occlusion reduced the anastomotic Qbr to .32 +/- .06% of CO (p < .05). Smoke inhalation injury resulted in a further increase in the maximal LPAP to 38 +/- 5 mmHg (p < .05 vs. right pulmonary artery pressure). The anastomotic Qbr rose to 1.29 +/- .13% of CO (p < .05) and was reduced to .40 +/- .09% of CO (p < .05) by BEA occlusion. Inhalation injury increased the anastomotic Qbr mainly due to BEA vasodilatation. Because the BEA supplies the injured airway, it may deliver deleterious material to the lung parenchyma.

Localization of cholinergic nerves in lower airways of guinea pigs using antisera to choline acetyltransferase.

Primary antiserum to choline acetyltransferase (ChAT), a specific marker for cholinergic nerves, was used to characterize the distribution of cholinergic nerve fibers and nerve cell bodies in guinea pig airways. ChAT immunoreactive nerve fibers were localized to the smooth muscle throughout the conducting airways and in the lamina propria of the trachea and large bronchi. Likewise, all nerve cell bodies in the ganglia intrinsic to the trachea and bronchi displayed a cholinergic phenotype. By contrast, ChAT immunoreactive nerve fibers were infrequently seen in the lamina propria of the peripheral airways and were absent in the airway epithelium. No evidence for colocalization of ChAT and the enzyme synthesizing the putative relaxant neurotransmitter nitric oxide was observed. These results provide further evidence for the key role played by cholinergic nerves in regulating airway smooth muscle tone and bronchial blood flow and provide further evidence that acetylcholine is not coreleased with the neurotransmitter(s) mediating relaxations of airway smooth muscle.

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.

This Month in the Journal

This Month in the Journal

How much oxygen does the human lung consume?

The amount of oxygen consumed by the lung itself is difficult to measure because it is included in whole-body gas exchange. It may be increased markedly under pathological conditions such as lung infection or adult respiratory distress syndrome. To estimate normal oxygen consumption of the human lung as a basis for further studies, respiratory gas analysis during total cardiopulmonary bypass may be a simple approach because the pulmonary circulation is separated from systemic blood flow during this period. Lung oxygen consumption was determined in 16 patients undergoing cardiac surgery. During total cardiopulmonary bypass their lungs were ventilated with low minute volumes (tidal volume, 150 ml; rate, 6 min-1; inspiratory oxygen fraction, 0.5; positive end-expiratory pressure, 3 mmHg). All expiratory gas was collected and analyzed by indirect calorimetry. As a reference value also, whole-body oxygen consumption of these patients was determined before total cardiopulmonary bypass. In a pilot study of eight additional patients (same ventilatory pattern), the contribution of systemic (bronchial) blood flow to pulmonary gas exchange during cardiopulmonary bypass was assessed. For this purpose, the amount of enflurance diffusing from the systemic blood into the bronchial system was measured. The human lung consumes about 5-6 ml oxygen per minute at an esophageal temperature of 28 degrees C. Prebypass whole-body oxygen consumption measured at nearly normothermic conditions was 198 +/- 28 ml/min. Mean lung and whole-body respiratory quotients were similar (0.84 and 0.77, respectively). Extrapolating lung oxygen consumption to 36 degrees C suggests that the lung consumes about 11 ml/min or about 5% of total body oxygen consumption. Because the amount of enflurane diffused from the systemic circulation into the bronchial system during cardiopulmonary bypass was less than 0.1%, the contribution of bronchial blood flow to lung gas exchange can be assumed to be negligible. The lung consumes about 5% of whole-body oxygen uptake.

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.