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.     

Temporal response of the fetal pulmonary circulation to pharmacologic vasodilators

To determine the temporal response of the fetal pulmonary circulation to pharmacologic vasodilators and to assess vasoreactivity following vasodilation, we infused either acetylcholine, histamine, or bradykinin directly into the left pulmonary artery of 21 chronically prepared fetal sheep. Blood flow (Q) to the left lung was measured by electromagnetic flow transducer. Left pulmonary artery infusion of acetylcholine at 1.5 micrograms.min-1 for 2 hr produced an increase in Q from 59 +/- 8 ml.min-1 to a peak of 113 +/- 10 ml.min-1 at 20 min into the infusion (P less than 0.001). After the peak at 20 min, Q steadily declined toward baseline to 66 +/- 7 ml.min-1 at the end of the 2-hr infusion period (P less than 0.01). Q in the 1/2-hr period following infusion was significantly less than the baseline period (47 +/- 6; P less than 0.04) with no change in pulmonary artery pressure. Similar patterns were seen with 2-hr infusions of histamine (150 ng.min-1) and bradykinin (100 ng.min-1). After a 2-hr infusion of one of the agents, a repeat infusion with that agent or a different one resulted in a diminished response. We conclude that fetal pulmonary vasodilation in response to local infusion of acetylcholine, histamine, or bradykinin is not sustained over a 2-hr period, and that following 2-hr exposure to vasodilators, pulmonary vascular resistance is increased and pulmonary vasoreactivity to pharmacologic vasodilators is decreased.     

Reduction of lung perfusion increases VA/Q heterogeneity

This study addresses the hypothesis that decreases in lung perfusion rate independently worsen gas exchange efficiency in an isolated left lower lobe in zone 2 conditions. In seven anesthetized dogs, the left lower lobe was isolated, leaving the bronchus and bronchial vasculature intact. Blood was taken from the femoral arteries and reinfused at a controlled rate into the pulmonary artery of the left lower lobe. The flow rate was varied between 100 and 400 ml/min. The multiple inert gas elimination technique was used to quantitate the matching of ventilation to perfusion. Reduction in lobe blood flow resulted in a significant increase in perfusion-related indexes of alveolar ventilation-perfusion heterogeneity, such as the log standard deviation of the perfusion distribution, the retention component of the arterial-alveolar difference area, and the retention dispersion index. The increased heterogeneity suggests a worsening of the intraregional matching between the ventilation and the perfusion when perfusion is less than normal.     

Pulmonary hemodynamics and lung water content during splanchnic ischemic shock

Pulmonary hemodynamics and lung water content were evaluated in open-chest dogs during splanchnic arterial occlusion (SAO) shock. Mean pulmonary arterial pressure [Ppa = 13.0 +/- 0.6 (SE) mmHg] and pulmonary venous pressure (4.1 +/- 0.2 mmHg) were measured by direct cannulation and the capillary pressure (Ppc = 9.0 +/- 0.6 mmHg) estimated by the double-occlusion technique. SAO shock did not produce a significant change in Ppa or Ppc despite a 90% decrease in cardiac output. An 18-fold increase in pulmonary vascular resistance occurred, and most of this increase (70%) was on the venous side of the circulation. No differences in lung water content between shocked and sham-operated dogs were observed. The effect of SAO shock was further evaluated in the isolated canine left lower lobe (LLL) perfused at constant flow and outflow pressure. The addition of venous blood from shock dogs to the LLL perfusion circuit caused a transient (10-15 min) increase in LLL arterial pressure (51%) that could be reversed rapidly with papaverine. In this preparation, shock blood produced either a predominantly arterioconstriction or a predominantly venoconstriction. These results indicate that both arterial and venous vasoactive agents are released during SAO shock. The consistently observed venoconstriction in the intact shocked lung suggests that other factors, in addition to circulating vasoactive agents, contribute to the pulmonary hemodynamic response of the open-chest shocked dog.     

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.     

Preconditioning modulates pulmonary endothelial dysfunction following ischemia-reperfusion injury in the rat lung: role of potassium channels

Ischemic preconditioning (IP) may protect the lung from ischemia-reperfusion (I/R) injury following cardiopulmonary by-pass and lung or heart transplantation. The present study was undertaken to investigate the role of ATP-dependent potassium channels (K(ATP)) in IP in the isolated buffer-perfused rat lung (IBPR) under conditions of elevated pulmonary vasoconstrictor tone (PVT). Since pulmonary arterial perfusion flow and left atrial pressure were constant, changes in pulmonary arterial pressure (PAP) directly reflect changes in pulmonary vascular resistance (PVR). When compared to control value, the pulmonary vasodilator responses to histamine and acetylcholine (ACh) following 2 h of hypothermic ischemia were significantly attenuated, whereas the pulmonary vasodilator response to sodium nitroprusside (SNP) was not altered. IP in the form of two cycles of 5 min of ischemia and reperfusion applied prior to the two-hour interval of ischemia, prevented the decrease in the pulmonary vasodilator responses to histamine and ACh. Pretreatment with glybenclamide (GLB) or HMR-1098, but not 5-hydroxydecanoic acid (5-HD), prior to IP abolished the protective effect of IP. In contrast, GLB or 5-HD did not significantly alter the pulmonary vasodilator response to histamine without IP pretreatment. The present data demonstrate that IP prevents impairment of endothelium-dependent vasodilator responses in the rat pulmonary vascular bed. The present data further suggest that IP may alter the mediation of the pulmonary vasodilator response to histamine and thereby trigger a mechanism dependent on activation of sarcolemmal, and not mitochondrial, K(ATP) channels to preserve endothelial-dependent vasodilator responses and protect against I/R injury in the lung.     

Is flow in subpleural region typical of the rest of the lung? A study using laser-Doppler flowmetry.

The microcirculation in the subpleural region of the lung is thought to be physiologically typical of the entire vasculature. To investigate this issue, an in situ blood-perfused dog lung lobe (500 ml/min) was prepared and the blood flow in the subpleural region (Qs) was monitored with laser-Doppler flowmetry (LDF). The flow rates into and out of the lobe were monitored with in-line flow probes, and the arterial and venous pressures were recorded from side ports in the cannulas. The LDF signal measures flow in arbitrary units over a region less than 2 mm deep and 1 mm2. The LDF signal was independent of site of measurement and was linearly proportional to total flow rate (r2 greater than 0.9), suggesting that during baseline conditions Qs behaves similarly to, although not necessarily the same as, blood flow in the rest of the lung. However, if the vasculature is constricted by serotonin (arterial constriction) or by histamine (venous constriction), Qs decreases significantly relative to total flow. In fact, in some cases Qs approached zero during vasoconstriction, despite the fact that total flow was maintained constant and the pulmonary arterial pressure became elevated. Reduction in Qs most likely reflects a redistribution from the subpleural to the central regions of the lung. The results of this study suggest that LDF is a useful tool for monitoring flow in the subpleural region of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal blood flow in normal dogs and in dogs with experimental liver cirrhosis following the acute continuous infusion of endotoxin

The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13-26 micrograms/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8-20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.     

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)     

Reduced sensitivity to beta-adrenergic agonists in Basenji-Greyhound dogs

To investigate the inhibitory effects of beta-adrenergic agonists and aminophylline on pulmonary responsiveness, we evaluated the ability of albuterol and aminophylline to attenuate pulmonary responses to aerosol challenge with methacholine and histamine in intact Basenji-Greyhound (BG) and selected mongrel dogs. Pulmonary responses were measured in untreated dogs and in dogs pretreated with albuterol (1 and 2.5 micrograms/kg) or aminophylline. Before aerosol challenge, baseline pulmonary resistance (RL) and dynamic compliance (Cdyn) were not significantly different between the BGs and the mongrels. In the untreated dogs, pulmonary responses to methacholine and histamine aerosols were not different between the BGs and the mongrels. Pretreatment with albuterol (1 microgram/kg) or aminophylline significantly attenuated the pulmonary response to methacholine in the mongrels but was without effect in the BGs. Albuterol (2.5 micrograms/kg) significantly attenuated the pulmonary response to methacholine in the BGs and the mongrels; however, this attenuation was significantly greater (P less than 0.05) in the mongrels than in the BGs. In response to histamine challenge, no differences were seen between the BGs and the mongrels in the control state (no pretreatment) or after pretreatment with albuterol or aminophylline. This study demonstrates that in BGs pulmonary responsiveness to methacholine but not histamine is resistant to inhibition by beta-adrenergic agonists. This may result from a qualitative or quantitative defect in either the cholinergic or beta-adrenergic receptor or to an abnormality distal to the receptors in the signal transduction mechanism at a site where the two signals interact.     

Relative contribution of bronchial flow to subpleural region in dog lung.

The bronchial flow is approximately 1% of the total pulmonary flow. Anastomosis between the bronchial and pulmonary vessels occurs primarily at the microcirculatory level. It is assumed that bronchopulmonary anastomoses are present in a homogeneous manner throughout lung parenchyma. To investigate this issue, an in situ blood-perfused left lower lung lobe (500 ml/min) was prepared in a live dog. The bronchial flow rate in the entire lobe was monitored using the rate of volume gain in the reservoir while the pulmonary and bronchial flow in the subpleural region was monitored using laser-Doppler flowmetry. The results were expressed as ratio of bronchial to pulmonary flow rate for the entire lobe and for the subpleural region. We found that, for the entire lobe, bronchial flow was 1.0% of pulmonary flow, while for the subpleural region this ratio was much higher, with an average of 12%. In two different experimental conditions that were imposed to affect the global bronchial flow, these ratios changed in the same direction as the global bronchial flow. After transfusion of blood into the animal, bronchial flow increased to 1.7%, while the subpleural bronchial flow increased to 18% of the subpleural pulmonary flow. During elevation of venous pressure, bronchial flow decreased to 0.6%, while the subpleural bronchial flow decreased to 10% of the subpleural pulmonary flow. The differences in the ratios between the global and subpleural region may be explained by having low pulmonary blood flow in the periphery compared with the interior regions of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular resistance and vasoactivity of gills and pulmonary artery of the salamander,Ambystoma tigrinum

Summary In order to understand the blood flow patterns and their regulation in the gills and pulmonary artery ofAmbystoma tigrinum, the vascular resistance and vasoactivity of the two major branchial perfusion pathways and a vascular plexus in the pulmonary artery were investigated using an isolated-tissue perfusion method. Acetylcholine and epinephrine were both pressor agents in all three vascular segments. Angiotensin II also constricted the branchial respiratory vasculature. Norephinephrine was primarily a vasodilator in the branchial respiratory vasculature, however, it had no effect on the shunt vessels of the gill or the pulmonary arterial plexus. Both gill circulations were insensitive to alterations in CO₂ and pH. Anoxia produced a slight vasodilation of the branchial respiratory vessels but had no effect on the shunt vasculature. Mild hypoxia had no effect on either branchial circulations. The results suggest that: (1) blood flow through the respiratory section of the gill may vary between 8 and 47% of total gill flow, (2) the major perfusion pathway to the lung is probably from the efferent artery of the third gill through the ductus arteriosus and then into the pulmonary artery, (3) O₂, CO₂ and pH exert no local control of branchial perfusion, (4) both cholinergic and adrenergic regulation of branchial and proximal pulmonary arterial vascular resistance is possible, (5) a rise in circulating norepinephrine should increase blood flow to the respiratory section of the gill.Abbreviations AII angiotensin II - ACh acetylcholine - EPi epinephrine - NE norepinephrine     

Role of pulmonary blood flow in postpneumonectomy lung growth.

To study the influence of blood flow on postpneumonectomy lung growth, we banded the left caudal lobe pulmonary artery of eight ferrets in such a way that blood flow to the caudal lobe did not increase when the right lung was excised 1 wk later. The fraction of the cardiac output received by the right lung before pneumonectomy was therefore directed entirely to the left cranial lobe. Three weeks after pneumonectomy the weight, volume, and protein and DNA contents of the two lobes of the left lung were measured and compared with those of five unoperated animals and eight animals after right pneumonectomy alone. Although its perfusion did not increase after pneumonectomy, the left caudal lobe of banded animals participated in compensatory growth, increasing in weight and protein and DNA contents. Although the cranial lobe of banded animals received 25% more of the cardiac output than the same lobe in pneumonectomized animals, cranial lobe volume and protein and DNA contents in the two groups were similar. Caudal lobes were smaller in banded than in simple pneumonectomized animals and tended to contain less protein, whereas the cranial lobes tended to be heavier. We conclude that increased pulmonary perfusion is not necessary for compensatory lung growth in adult ferrets, but it may modify this response.     

The effect of closing the ductus arteriosus on the pulmonary circulation of the fetal sheep

In the mammalian fetus the ductus arteriosus allows right ventricular output to be shunted away from the lungs to the systemic circulation. This study was performed to determine how closing the ductus arteriosus of the fetal sheep would affect the pulmonary circulation. Under halothane anaesthesia 6 near-term fetal sheep were delivered with the umbilical circulation intact. Catheters were placed in the right atrium, the pulmonary artery, and the aorta. Pulmonary blood flow was measured by injecting radioactive microspheres into the right atrium while a reference sample was withdrawn from the pulmonary artery. Closing the ductus arteriosus increased pulmonary arterial pressure by 22% from 51 +/- 3 to 62 +/- 3 mmHg and increased pulmonary blood flow disproportionately by 198% from 232 +/- 74 to 692 +/- 80 ml/min per 100g. Thus, pulmonary vascular resistance decreased by 75% from 0.451 +/- 0.65 to 0.095 +/- 0.010 mmHg 100g min/ml. These findings extend the observation that pressure and flow in the pulmonary circulation of the air-breathing lung do not have a linear relationship passing through the origin to include a striking example in the fluid-filled lung of the intact fetus. They also raise questions about the nature of the elevated vascular resistance in the fetal lung.     

Neutrophil retention in model capillaries: deformability, geometry, and hydrodynamic forces

The initial retention of neutrophils within the pulmonary microvascular bed occurs in both physiological and pathological states, yet the factors responsible for this retention are poorly understood. Because the diameter of the neutrophil is approximately 7.03 micron and the mean pulmonary capillary diameter is 5.5 micron, we postulated that geometric constraints imposed by the microvascular bed, the deformability of the neutrophil, and the hydrodynamic characteristics of blood were important determinants of neutrophil retention. We used a filtration system wherein 111In-labeled human neutrophils (111In-N) suspended in a serum-containing buffer were passed through Nuclepore filters of known pore size. Compared with 99mTc-labeled erythrocytes (99mTc-RBC), the passage of 111In-N was delayed and a higher percentage was retained within the filter. Because the neutrophil and RBC are approximately equal in diameter, the deformability of the neutrophil must be less than that of RBC. As the flow rate increased, retention in the filters decreased logarithmically from 72 +/- 5% (flow rate 0.5 ml/min) to 15 +/- 4% (10.0 ml/min). As the number of RBC in the buffer increased, neutrophil retention in 5-micron filters decreased in a linear fashion from 65 +/- 6% at hematocrit of 0 to 33 +/- 2% at hematocrit of 10. The perfusion pressure and shear stress were of critical importance, and there was a logarithmic relationship between retention and perfusion pressure or shear stress (tau), whether the increase in pressure or tau was generated by increasing flow or by increasing the hematocrit of the perfusate. As the pore size of the filter increased, the retention of neutrophils decreased in a logarithmic fashion: from 75 +/- 5% in the 3-micron filter to 4 +/- 1.3% in the 12-micron filter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histamine release and circulating cells after antigen inhalation in allergic dogs

Histamine can be recovered from the blood of ragweed-sensitized dogs after aerosol antigen challenge, although its source is unknown. Neutrophils and eosinophils have been recovered from bronchoalveolar lavage fluid (BALF) obtained under identical conditions. We investigated the time course of changes in histamine levels in plasma and BALF taken from ragweed-sensitized dogs after aerosol challenge. Changes in the numbers of circulating neutrophils, eosinophils, lymphocytes, monocytes, and platelets were also studied. After 3 min, total pulmonary resistance (RL) was maximally increased and systolic blood pressure was maximally decreased. Histamine levels in plasma and BALF were increased and circulating eosinophils and neutrophils were decreased. After 15 min, platelet numbers were reduced. By 90 min, changes in RL, blood pressure, plasma and BALF histamine concentrations, and circulating neutrophils and eosinophils had returned to base-line values, but platelet numbers remained significantly decreased. Sham challenge caused no significant changes in any of these variables. Intravenous administration of histamine in doses large enough to attain plasma levels comparable with those achieved after aerosol antigen challenge resulted in no concomitant rise in BALF histamine levels. We conclude that antigen challenge in sensitized dogs causes increases in BALF and plasma histamine levels and is associated with a reduction in circulating neutrophils, eosinophils, and platelets. It is likely that antigen causes airway mast cells to release mediators that move down a concentration gradient from the airways to the pulmonary circulation.     

Upstream pressure for systemic to pulmonary flow from bronchial circulation in dogs

Systemic to pulmonary flow from bronchial circulation, important in perfusing potentially ischemic regions distal to pulmonary vascular obstructions, depends on driving pressure between an upstream site in intrathoracic systemic arterial network and pulmonary vascular bed. The reported increase of pulmonary infarctions in heart failure may be due to a reduction of this driving pressure. We measured upstream element for driving pressure for systemic to pulmonary flow from bronchial circulation by raising pulmonary venous pressure (Ppv) until the systemic to pulmonary flow from bronchial circulation ceased. We assumed that this was the same as upstream pressure when there was flow. Systemic to pulmonary flow from bronchial circulation was measured in left lower lobes (LLL) of 21 anesthetized open-chest dogs from volume of blood that overflowed from pump-perfused (90-110 ml/min) pulmonary vascular circuit of LLL and was corrected by any changes of LLL fluid volume (wt). Systemic to pulmonary flow from bronchial circulation upstream pressure was linearly related to systemic arterial pressure (slope = 0.24, R = 0.845). Increasing Ppv caused a progressive reduction of systemic to pulmonary flow from bronchial circulation, which stopped when Ppv was 44 +/- 6 cmH2O and pulmonary arterial pressure was 46 +/- 7 cmH2O. A further increase in Ppv reversed systemic to pulmonary flow from bronchial circulation with blood flowing back into the dog. When net systemic to pulmonary flow from bronchial circulation by the overflow and weight change technique was zero a small bidirectional flow (3.7 +/- 2.9 ml.min-1 X 100 g dry lobe wt-1) was detected by dispersion of tagged red blood cells that had been injected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of ductus venosus in distribution of umbilical blood flow in human fetuses during second half of pregnancy

Color Doppler sonography was used to study umbilical and ductus venosus (DV) flow in 137 normal fetuses between 20 and 38 wk of gestation. Hepatic flows were also evaluated. In all parts of the venous circulation examined, blood flow increased significantly with advancing gestational age. The weight-specific amniotic umbilical flow did not change significantly during gestation (120 +/- 44 ml. min(-1). kg(-1)), whereas DV flow decreased significantly (from 60 to 17 ml. min(-1). kg(-1)). The percentage of umbilical blood flow shunted through the DV decreased significantly (from 40% to 15%); consequently, the percentage of flow to the liver increased. The right lobe flow changed from 20 to 45%, whereas the left lobe flow was approximately constant (40%). These changes are related to different patterns of growth of the umbilical veins and DV diameters. The present data support the hypothesis that the DV plays a less important role in shunting well-oxygenated blood to the brain and myocardium in late normal pregnancy than in early gestation, which leads to increased fetal liver perfusion.     

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)     

The interdependent contributions of gravitational and structural features to perfusion distribution in a multiscale model of the pulmonary circulation

Recent experimental and imaging studies suggest that the influence of gravity on the measured distribution of blood flow in the lung is largely through deformation of the parenchymal tissue. To study the contribution of hydrostatic effects to regional perfusion in the presence of tissue deformation, we have developed an anatomically structured computational model of the pulmonary circulation (arteries, capillaries, veins), coupled to a continuum model of tissue deformation, and including scale-appropriate fluid dynamics for blood flow in each vessel type. The model demonstrates that both structural and the multiple effects of gravity on the pulmonary circulation make a distinct contribution to the distribution of blood. It shows that postural differences in perfusion gradients can be explained by the combined effect of tissue deformation and extra-acinar blood vessel resistance to flow in the dependent tissue. However, gravitational perfusion gradients persist when the effect of tissue deformation is eliminated, highlighting the importance of the hydrostatic effects of gravity on blood distribution in the pulmonary circulation. Coupling of large- and small-scale models reveals variation in microcirculatory driving pressures within isogravitational planes due to extra-acinar vessel resistance. Variation in driving pressures is due to heterogeneous large-vessel resistance as a consequence of geometric asymmetry in the vascular trees and is amplified by the complex balance of pressures, distension, and flow at the microcirculatory level.