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.     

Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax

Carvalho, Paula, Jacob Hildebrandt, and Nirmal B. Charan.Changes in bronchial and pulmonary arterial blood flow with progressive tension pneumothorax. J. Appl.Physiol. 81(4): 1664-1669, 1996.We studied theeffects of unilateral tension pneumothorax and its release on bronchialand pulmonary arterial blood flow and gas exchange in 10 adultanesthetized and mechanically ventilated sheep with chronicallyimplanted ultrasonic flow probes. Right pleural pressure (Ppl) wasincreased in two steps from 5 to 10 and 25 cmH₂O and then decreased to 10 and5 cmH₂O. Each level of Pplwas maintained for 5 min. Bronchial blood flow, right and leftpulmonary arterial flows, cardiac output(T),hemodynamic measurements, and arterial blood gases were obtained at theend of each period. Pneumothorax resulted in a 66% decrease inT, bronchialblood flow decreased by 84%, and right pulmonary arterial flowdecreased by 80% at Ppl of 25 cmH₂O(P < 0.001). At peak Ppl, themajority ofT was due toblood flow through the left pulmonary artery. With resolution ofpneumothorax, hemodynamic parameters normalized, although abnormalitiesin gas exchange persisted for 60-90 min after recovery and wereassociated with a decrease in total respiratory compliance.

     

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)     

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)     

Cerebral blood flow velocity response to induced and spontaneous sudden changes in arterial blood pressure

The influence of different types of maneuvers that can induce sudden changes of arterial blood pressure (ABP) on the cerebral blood flow velocity (CBFV) response was studied in 56 normal subjects (mean age 62 yr, range 23-80). ABP was recorded in the finger with a Finapres device, and bilateral recordings of CBFV were performed with Doppler ultrasound of the middle cerebral arteries. Recordings were performed at rest (baseline) and during the thigh cuff test, lower body negative pressure, cold pressor test, hand grip, and Valsalva maneuver. From baseline recordings, positive and negative spontaneous transients were also selected. Stability of PCO2 was monitored with transcutaneous measurements. Dynamic autoregulatory index (ARI), impulse, and step responses were obtained for 1-min segments of data for the eight conditions by fitting a mathematical model to the ABP-CBFV baseline and transient data (Aaslid's model) and by the Wiener-Laguerre moving-average method. Impulse responses were similar for the right- and left-side recordings, and their temporal pattern was not influenced by type of maneuver. Step responses showed a sudden rise at time 0 and then started to fall back to their original level, indicating an active autoregulation. ARI was also independent of the type of maneuver, giving an overall mean of 4.7 +/- 2.9 (n = 602 recordings). Amplitudes of the impulse and step responses, however, were significantly influenced by type of maneuver and were highly correlated with the resistance-area product before the sudden change in ABP (r = -0.93, P < 0.0004). These results suggest that amplitude of the CBFV step response is sensitive to the point of operation of the instantaneous ABP-CBFV relationship, which can be shifted by different maneuvers. Various degrees of sympathetic nervous system activation resulting from different ABP-stimulating maneuvers were not reflected by CBFV dynamic autoregulatory responses within the physiological range of ABP.     

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.     

Senescence alters blood flow responses to acute heat stress

Renal and splanchnic sympathetic nerve discharge (SND) responses to heating are significantly reduced in senescent compared with young Fischer-344 (F344) rats (Kenney MJ and Fels RJ. Am J Physiol Regul Integr Comp Physiol 283: R513-R520, 2002). However, the functional significance of this finding is not known. We tested the hypothesis that blood flow distribution profiles to heating are altered in senescent (24 mo old) compared with mature (12 mo old) and young (3 mo old) F344 rats. Visceral organ, skeletal muscle, and tail blood flows were determined with the radionuclide-tagged microsphere technique before (control, 38 degrees C) and during heating that increased body temperature to 41 degrees C in anesthetized F344 rats. Vascular conductance in the kidney, stomach, large intestine, pancreas, spleen, and tail was significantly reduced during control before heating in senescent compared with young F344 rats. Heating significantly decreased kidney, stomach, small and large intestine, and pancreas vascular conductance in young and mature but not senescent F344 rats. Vascular conductance at 41 degrees C in the kidney and small intestine was significantly lower and in the stomach tended to be lower in young compared with senescent rats. Splenic conductance increased during heating in young and senescent rats but was highest in young rats. Tail conductance during heating was significantly increased in young rats but remained unchanged in mature and senescent rats. These results demonstrate a marked attenuation in heating-induced vascular conductance changes in senescent rats, suggesting an important functional consequence for the attenuated SND responses to heating in aged rats.     

Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta -agonists

Carvalho, Paula, Shane R. Johnson, Nirmal B. Charan.Non-cAMP-mediated bronchial arterial vasodilation in response toinhaled -agonists. J. Appl.Physiol. 84(1): 215-221, 1998.We studied thedose-dependent effects of inhaled isoetharine HCl, a -adrenergicbronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow(br) in anesthetized sheep. Isoetharine resulted ina dose-dependent increase in br. With atotal dose of 17.5 mg, br increased from baselinevalues of 22 ± 3.4 (SE) to 60 ± 16 ml/min(P < 0.001), an effect independentof changes in cardiac output and systemic arterial pressure. To furtherstudy whether synthesis of endogenous nitric oxide (NO) affects-agonist-induced increases in br, weadministered isoetharine (20 mg) by inhalation before and after theNO-synthase inhibitorN-nitro-L-argininemethyl ester (L-NAME).Intravenous L-NAME (30 mg/kg) rapidly decreased br by ~80% of baseline,whereas L-NAME via inhalation(10 mg/kg) resulted in a delayed and smaller (~22%) decrease.Pretreatment with L-NAME viaboth routes of administration attenuated bronchial arterialvasodilation after subsequent challenge with isoetharine. We concludethat isoetharine via inhalation increases br in adose-dependent manner and that -agonist-induced relaxation ofvascular smooth muscle in the bronchial vasculature is partiallymediated via synthesis of NO.

     

Dynamic response of local pulmonary blood flow to alveolar gas tensions: experiment

The purpose of this study was to investigate the mechanism that causes a damped oscillatory response of local pulmonary blood flow to local hypoxia. The left lower lobe (LLL) of 10 anesthetized dogs was ventilated independently but synchronously with the rest of the lungs. Blood flow to the LLL as a proportion of total flow (QLLL/QT) was measured during the on-transient of the hypoxic response when LLL inspirate was changed from O2 to N2. There was a damped oscillatory response of QLLL/QT to hypoxia (34 of 40 trials). In contrast, the off-transient was always monotonic. There was no enhancement of the steady state or dynamic hypoxic response with repeated challenges. Local alveolar hypercapnia caused a damped oscillatory response in the presence of local hypoxia (15 of 20 trials), but there was no response in the presence of local hyperoxia. We conclude that 1) the dynamic pulmonary vascular response to O2 and CO2 are not additive because the response to CO2 is attenuated by hyperoxia and 2) the damped oscillatory response that occurs during hypoxia is the result of changes of local alveolar CO2 per se.     

Analysis of pulmonary arterial pressure profile after occlusion of pulsatile blood flow

In isolated canine lung lobes perfused with a pulsatile pump, arterial occlusions were performed and the postocclusion arterial pressure profiles were analyzed to estimate the pulmonary capillary pressure. A solenoid valve interposed between the pump and the lobar artery was used to perform arterial occlusions at several instants equally distributed within a pressure cycle. Double occlusions were also accomplished by simultaneously activating the solenoid valve and clamping the venous outflow of the lung lobe. To analyze an arterial occlusion pressure profile, we computed the best monoexponential fit of the pressure decay over a short period of time after the occlusion maneuvers. Two estimates of the capillary pressure were derived from this analysis: 1) the extrapolation of the exponential fit to the instant of occlusion, and 2) the point at which the recorded pressure decay curve merges with the exponential fit. The pressures thus determined were compared with the double occlusion pressure that provided an independent estimate of the pulmonary capillary pressure. Our results show that, under a wide range of conditions, the estimates of the capillary pressure obtained from the arterial occlusion data are nearly equal to the double occlusion pressures. Additionally, we estimated the capillary pressure variations within a pressure cycle by examining the occlusion pressures sampled at different instants of the cycle. The pulsatility of the pulmonary microvascular pressure varied with the pump frequency as well as the state of arterial and venous vasoaction. These variations are consistent with the representation of the lung vasculature as a low-pass filter.     

Measurements of bronchial arterial flow and bronchopulmonary flow at high altitudes

The bronchial arterial and bronchopulmonary flows were measured in sheep born and bred at altitudes above 4,000 m and sheep from sea level.Both flows were 50% smaller in animals of high altitudes. This phenomenon seems to be part of the normal mechanism of adaptation to life at high altitudes. The decrease of the bronchopulmonary flow implies a diminution of the venous admixture into the left heart,and could contribute to some extent to the maintenance of an almost null gradient of oxygen between the alveolar air and the arterial blood,which is characteristic of adaptation to life At high altitudes.

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Zusammenfassung Der bronchoarterielle und bronchopulmonale Durchfluss wurde an in Seehöhe und 4.000 m Höhe einheimischen Schafen gemessen. Die Werte waren bei den Hochgebirgs-Schafen 50% niedriger als bei den Schafen der Niederungen.Diese Verminderung scheint eine der normalen Reaktionen bei der sich über Generationen erstreckenden Anpassung des Organismus an das Leben in grossen Höhen zu sein. Die Verminderung des bronchopulmonalen Durchflusses führt zur Verkleinerung der venösen Beimischung im linken Herzen und kann dazu beitragen, das Sauerstoff-Gefälle zwischen der Alveolarluft und dem arteriellen Blut, wie es für die bestehende Akklimatisation an die Höhe charakteristisch ist' bei fast null zu halten.

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Resume On a mesuré les circulations bronco artérielle et bronchopulmonaire chez les mountons nés et élevés les uns au niveau de la mer et les autres à haute altitude, audessus de 4.000 m. Chez les moutons de haute montagne la quantité de sang relevée dans les deux circulations étaient de 50% plus basses que chez ceux de la plaine.Ce phenomène semble faire partie de mécanisme normal d'adaptation à la vie à haute altitude. L'abaissement de la circulation bronchopulmonaire entraîne une diminution du mélange veneux dans le ventricule gauche et peut contribuer dans une certaine mesure à maintenir aux environs de zéro la différence de teneur en oxygène entre l'air alvéolaire et le sang artériel,ce qui constitue une des charactéristiques de l'adaptation à la vie à haut altitude.

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This investigation was supported by the P.H.S. Research Grant No. 08732-01, from the National Heart Institute, Public Health Service, U.S.A.     

Exercise alters fractal dimension and spatial correlation of pulmonary blood flow in the horse.

We determined the changes in fractal dimensions and spatial correlations of regional pulmonary blood flow with increasing exercise in race horses (n = 4) by using 15-microm fluorescent microspheres. Fluorescence was measured to quantitate regional blood to 1.3-cm(3) samples (n = 1,621-2,503). Perfusion distributions were characterized with fractal dimensions (a measure of spatial variability) and spatial correlations. On average, the fractal dimension decreased with exercise (trot 1.216 to gallop 1.173; P < 0. 05) despite a variable fractal dimension at rest. Spatial correlation of flow to neighboring pieces increased with exercise (trot 0.57 +/- 0.074 to gallop 0.73 +/- 0.051) and was inversely correlated with fractal dimension, indicating better spatial correlation as blood flow distribution becomes more uniform. This is the first study to document a change in fractal dimension as a result of increasing pulmonary blood flow. Spatial differences in response to vasoregulatory mediators may play a role in this phenomenon.     

Angiogenesis in bronchial circulatory system after unilateral pulmonary artery obstruction

Charan, Nirmal B., and Paula Carvalho. Angiogenesis inbronchial circulatory system after unilateral pulmonary artery obstruction. J. Appl. Physiol. 82(1):284-291, 1997.We studied the effects of left pulmonary artery(LPA) ligation on the bronchial circulatory system (BCS) by using asheep model. LPA was ligated in the newborn lambs soon after birth(n = 8), and when the sheep were ~3yr of age anatomic studies revealed marked angiogenesis in BCS.Bronchial blood flow and cardiac output were studied by placing flowprobes around the bronchial and pulmonary arteries in four adult sheep.After LPA ligation, bronchial blood flow increased from 35 ± 6 to134 ± 42 ml/min in ~3 wk (P < 0.05). We also studied gas-exchange functions of BCS ~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 was16 ± 3 ml/min and was similar to the chronic model, whereasCO₂ 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 iscapable of performing some gas-exchange functions.

     

Small disturbance in arterial blood flow

The behaviour of a small disturbance in an arterial blood flow has been studied analytically. The growth equation governing growth or decay of a disturbance has been obtained and solved. The behaviour of wave amplitude has been investigated as the wave propagates in time. The application of results to the human arterial system shows that the shock waves are not expected under normal physiological conditions. In the case of a pathologically increased pressure rise at the root of aorta, shock-like transitions may develop in the periphery. It is observed that the friction effects are to resist the tendency of shock formation in arteries.