Effect of zonal conditions and posture on pulmonary blood flow distribution to subpleural and interior lung.

Observations made on vessels seen directly beneath the pleura may not accurately reflect what occurs in vessels located deeper in the interior of the lung. We quantified flow to subpleural and deeper, interior regions under zone 1 or 2 conditions in excised (n = 5) and in vivo (n = 6) rabbit lungs, in the head-up or inverted position. After infusion of radiolabeled microspheres, lungs were dried at alveolar pressure of 25 cmH(2)O and sliced in 1-cm sections along the gravitational plane and in three planes in the dorsal-ventral axis. Regions located <1 mm from the pleural surface were dissected away from the remaining tissue. In both zonal conditions, 1) weight-normalized flow to the interior exceeded that found in subpleural regions; and 2) flow followed the gravitational gradient, with the correlation varying with the scale of measurement. We conclude that flow through subpleural vessels is less than that which occurs deeper in the interior, but the regional distributions of flow and the effects of zonal conditions are similar in the two regions.     

Bronchial vascular contribution to lung lymph flow

The lymphatic vessels of thelung provide an important route for clearance of interstitial edemafluid filtered from pulmonary blood vessels. However, the importance oflung lymphatics for the removal of airway liquid filtered from thesystemic circulation of the lung has not been demonstrated. We studiedthe contribution of the bronchial vasculature to lung lymph flow inanesthetized, ventilated sheep (n = 35). With the bronchial artery cannulated and perfused (control flow = 0.6 ml · min¹ · kg¹),lymph flow from the efferent duct of the caudal mediastinal lymph nodewas measured 1) during increasedbronchial vascular perfusion (300% of control flow);2) with a hydrated interstitium induced by a 1-h period of left atrial hypertension and subsequent recovery, both with and without bronchial perfusion; and3) during infusion (directly intothe bronchial artery) of bradykinin, an inflammatory mediator known tocause changes in bronchial vascular permeability. Increased bronchialperfusion for 90 min resulted in an average 35% increase in lung lymphflow. During left atrial hypertension, the increase in lung lymph flowwas significantly greater with bronchial perfusion (339% increase overbaseline) than without bronchial perfusion (138% increase).Furthermore, recovery after left atrial hypertension was more completeafter 90 min without bronchial perfusion (91%) than with bronchialperfusion (63%). Infusion of bradykinin into the bronchial arteryresulted in a prompt and prolonged 107% increase in lung lymph flow.This was not seen if the same dose was infused into the pulmonaryartery. Thus bronchial vascular transudate contributes significantly to lymph flow from the efferent duct of the caudal mediastinal lymph node.These results demonstrate that lymph vessels clear excess fluid fromthe airway wall and should be considered when evaluating the effect ofvascular leak in airway obstruction.

     

Systemic blood flow to the lung after bronchial artery occlusion in anesthetized sheep.

To compare the effectiveness of different embolizing agents in reducing or redistributing bronchial arterial blood flow, we measured systemic blood flow to the right lung and trachea in anesthetized sheep by use of the radioactive microsphere method before and 1 h after occlusion of the bronchoesophageal artery (BEA) as follows: injection of 4 ml ethanol (ETOH) into BEA (group 1, n = 5), injection of approximately 0.5 g polyvinyl alcohol particles (PVA) into BEA (group 2, n = 5), or ligation of BEA (group 3, n = 5). After occlusion, angiography showed complete obstruction of the bronchial vessels. There were no changes in tracheal blood flow in any of the groups. Injection of ETOH produced a 75 +/- 14% (SD) reduction in flow to the middle lobe (P less than 0.02) and a 75 +/- 13% reduction to the caudal lobe (P less than 0.01), whereas injection of PVA produced a smaller reduction in flow to these two lobes (41 +/- 66 and 51 +/- 54%, respectively). After BEA ligation there was a 52 +/- 29% reduction in flow to the middle lobe and a 53 +/- 38% reduction to the caudal lobe (P less than 0.05). This study has significant implications both clinically and experimentally; it illustrates the importance of airway collateral circulation, in that apparently complete radiological obstruction of the BEA does not necessarily mean complete obstruction of systemic blood flow. We also conclude that, in experimental studies in which the role of the bronchial circulation in airway pathophysiology is examined, ETOH is the agent of choice.     

Human bronchial artery blood flow after lung Tx with direct bronchial artery revascularization.

The inaccuracy of measuring human bronchial artery blood flow has previously been considerable. En bloc double-lung transplantation with bronchial artery revascularization (BAR) using a single conduit offers the unique opportunity of direct measurement of the total bronchial artery blood flow. In eight en bloc double-lung-transplanted patients with complete BAR, the basal blood flow was measured by using a 0.014-in. Doppler guide wire and arteriography. The average peak velocity in the conduit was 12-73 cm/s [+/-2.1 (SD) cm/s], and the conduit diameter was 1.7-3.1 mm [+/-0.10 (SD) mm], giving individual basal flow values between 19 and 67 ml/min [+/-5 (SD) ml/min], or 0.2-1.9% of estimated cardiac output. In three patients basal measurements were followed by injection of nitroglycerin and verapamil into the conduit. This increased the bronchial artery flow to 121-262% of basal values (31-89 ml/min). The measured values appear more physiologically plausible than previous bronchial artery blood flow measurements in humans.     

Relative contribution of gravity to pulmonary perfusion heterogeneity.

We designed a series of experiments and analyses to quantify the contribution of gravity to pulmonary perfusion heterogeneity. Regional pulmonary perfusion was measured in five anesthetized and ventilated dogs in both supine and prone positions by use of radiolabeled microspheres injected during apnea at functional residual capacity. Measurements of flow were repeated in each position, and the sequence of positions was prospectively designed to nullify any effect of order. The lungs of each animal were excised, perfused with saline until clear, dried at an inflation pressure of 25 cmH2O, and cut into 1.9-cm3 pieces. Each piece was weighed and the radioactivity determined in a scintillation counter. Measurement errors were minimized by excluding lung pieces that had greater than 25% airway and weighed less than 10 mg or greater than 60 mg. Weight-normalized flows in each position and repetition were determined for each lung piece. An analysis of variance model was used to identify the percentage of variation in regional flow that was due to position (supine vs. prone), to random error and time (measurement and repetition), and to structure, where structure was defined as the component of flow that remained constant across position and replication. The contributions of position, error/time, and structure to the total variability of flow across the five dogs were 7.8 +/- 0.6, 8.4 +/- 8.3, and 83.8 +/- 8.4%, (SD), respectively. Because the contribution of position represents the additive effect of gravity between two opposite positions, the contribution of gravity to perfusion heterogeneity in one position may be as little as 4%.(ABSTRACT TRUNCATED AT 250 WORDS)     

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)     

No gravity-independent gradient of blood flow distribution in dog lung

The existence of a major gravity-independent gradient of blood flow in lungs has recently been described based on single photon emission computed tomography after intravenous injection of radioactively labeled macroaggregates. We wanted to test this hypothesis of a major gravity-independent gradient in lung blood flow in experiments with direct measurement of macroaggregate distribution in the dog lung. In six anesthetized (4 prone spontaneously breathing, 2 mechanically ventilated) dogs we injected 111In-labeled albumin macroaggregates intravenously. We killed the dogs, removed, inflated, and froze the lower lobes. We sliced the lobes 1 cm thick and made gamma camera images of the slices. We then cut three or four slices in each lobe into two or three concentric layers and measured the radioactivity per gram of tissue in a well-type gamma counter. In three of the dogs we also labeled the red cells (99mTc) so that blood volume in each sample could be determined. The gamma camera images were acquired on a 64 X 64 matrix with 4 X 4 mm pixels. On the numeric printouts from the individual slices we made two or three concentric layers and calculated activity per pixel in each layer. Neither by the well counting nor by the pixel analysis of the gamma scans did we detect any gravity-independent distribution of blood flow. With the well counting the distribution was the same whether macroaggregate activity was expressed per gram of tissue or per gram of blood-free tissue. We conclude that by direct measurements no major gravity-independent gradient of pulmonary blood flow can be detected in dog lungs.     

Relative contribution of neurotransmission failure to diaphragm fatigue

Two procedures were used to estimate the relative contribution of neurotransmission failure (NF) to fatigue of the rat diaphragm at different rates of phrenic nerve stimulation. In one, direct muscle stimulation was intermittently superimposed on neural stimulation of the diaphragm, and the relative contribution of NF was estimated by the difference in generated tension. In a second procedure, diaphragm fatigue was induced by using either direct muscle stimulation (with complete blockade of the neuromuscular junction by d-tubocurare) or phrenic nerve stimulation. The relative contribution of NF to diaphragm fatigue was then estimated by comparing the force loss during these two modes of stimulation. With both procedures, it was observed that 1) the relative contribution of NF to diaphragm fatigue was less than 45% at each frequency of phrenic nerve stimulation; 2) the relative contribution of NF to diaphragm fatigue increased at higher rates of phrenic stimulation, reaching a maximum at 75 pulses/s; and 3) the relative contribution of NF to diaphragm fatigue reached a plateau after 2 min of repetitive stimulation.     

A method for microinjection into subpleural alveoli of rat lung in situ

A new technique is described for the micropuncture of rat lung in the intact thorax. Under pentobarbital sodium anesthesia a glass micropipette is passed through a small area of the parietal pleura, which has been cleared of overlying intercostal muscle. The micropipette is passed into the lung parenchyma and withdrawn again without collapsing the lung. The current application of this technique is in the microinjection of fluid into subpleural alveoli, which is illustrated using a suspension of colloidal gold. The gold particles are immediately dispersed over the surface of many alveoli, a small proportion spreading laterally as far as 4-6 mm. There is no evidence of alveolar flooding.     

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.