L-NAME does not affect exercise-induced pulmonary hypertension in Thoroughbred horses

The present study was carried out to examine theeffects of nitric oxide synthase inhibition withN-nitro-L-arginine methyl ester(L-NAME) on the right atrial as well as on the pulmonary arterial, capillary, and venous blood pressures of horses during rest and exercise performed at maximal heartrate (HR_max). Experiments werecarried out on seven healthy, sound, exercise-trained Thoroughbredhorses. Using catheter-tip manometers, with signals referenced at thepoint of the shoulder, we determined phasic and mean right atrial andpulmonary vascular pressures in two sets of experiments [control(no medications) and L-NAME (20 mg/kg iv given 10 min before exercise studies)]. The studies werecarried out in random order 7 days apart. Measurements were made atrest and during treadmill exercise performed on a 5% uphill grade at6, 8, and 14.2 m/s. Exercise on a 5% uphill grade at 14.2 m/s elicitedHR_max and could not be sustainedfor >90 s. In quietly standing horses,L-NAME administration caused asignificant rise in right atrial, as well as pulmonary arterial, capillary, and venous pressures. This indicates that nitric oxide synthase inhibition modifies the basal pulmonary vasomotor tone. Inboth treatments, exercise caused progressive significant increments inright atrial and pulmonary vascular pressures, but the values recordedin the L-NAME study were notdifferent from those in the control study. The extent ofexercise-induced tachycardia was significantly decreased in theL-NAME study at 6 and 8 m/s butnot at 14.2 m/s. Thus, L-NAMEadministration may not modify the equine pulmonary vascular tone duringexercise at HR_max. However, asindicated by a significant reduction in heart rate,L-NAME seems to modify thesympathoneurohumoral response to submaximal exercise.

     

PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat

In vivo pulmonary arterialcatheterization was used to determine the mechanism by whichplatelet-activating factor (PAF) produces pulmonary edema inrats. PAF induces pulmonary edema by increasing pulmonarymicrovascular permeability (PMP) without changing the pulmonarypressure gradient. Rats were cannulated for measurement of pulmonaryarterial pressure (Ppa) and mean arterial pressure. PMP wasdetermined by using either in vivo fluorescent videomicroscopy or theex vivo Evans blue dye technique. WEB 2086 was administeredintravenously (IV) to antagonize specific PAF effects. Threeexperiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAFinduced systemic hypotension with a decrease in Ppa. PMP increasedafter IV PAF in a dose-related manner. Topical PAF increased PMP butdecreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa(50 ± 3%) increased during E. coli bacteremia.PAF-receptor blockade prevents changes in Ppa and PMP after bothtopical PAF and E. coli bacteremia. PAF, which has beenshown to mediate pulmonary edema in prior studies, appears to act inthe lung by primarily increasing microvascular permeability. Thepresence of PAF might be prerequisite for pulmonary vascularconstriction during gram-negative bacteremia.

     

Very high pressures are required to cause stress failure of pulmonary capillaries in Thoroughbred racehorses

Birks, Eric K., Odile Mathieu-Costello, Zhenxing Fu, WalterS. Tyler, and John B. West. Very high pressures are required tocause stress failure of pulmonary capillaries in Thoroughbred racehorses. J. Appl. Physiol. 82(5):1584-1592, 1997.Thoroughbred horses develop extremely highpulmonary vascular pressures during galloping, all horses in trainingdevelop exercise-induced pulmonary hemorrhage, and we have shown thatthis is caused by stress failure of pulmonary capillaries. It is knownthat the capillary transmural pressure (Ptm) necessary for stressfailure is higher in dogs than in rabbits. The present study wasdesigned to determine this value in horses. The lungs from 15 Thoroughbred horses were perfused with autologous blood at Ptm values(midlung) of 25, 50, 75, 100 and 150 mmHg, and then perfusion fixed,and samples (dorsal and ventral, from caudal region) were examined byelectron microscopy. Few disruptions of capillary endothelium wereobserved at Ptm  75 mmHg, and 5.3 ± 2.2 and 4.3 ± 0.7 breaks/mm endothelium were found at 100 and 150 mmHg Ptm, respectively.Blood-gas barrier thickness did not change with Ptm. At low Ptm,interstitial thickness was greater than previously found in rabbits butnot in dogs. We conclude that the Ptm required to cause stress failureof pulmonary capillaries is between 75 and 100 mmHg and is greater inThoroughbred horses than in both rabbits and dogs.

     

Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds.

The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O2 content increased significantly with exercise in both treatments, while the mixed venous blood O2 content decreased as O2 extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.     

Effect of prior high-intensity exercise on exercise-induced arterial hypoxemia in Thoroughbred horses.

Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pulmonary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was carried out to examine whether the structural changes in the blood-gas barrier caused by a prior bout of high-intensity short-term exercise capable of inducing EIPH would affect the arterial hypoxemia induced during a successive bout of exercise performed at the same workload. Two sets of experiments, double- and single-exercise-bout experiments, were carried out on seven healthy, sound Thoroughbred horses. Experiments were carried out in random order, 7 days apart. In the double-exercise experiments, horses performed two successive bouts (each lasting 120 s) of galloping at 14 m/s on a 3.5% uphill grade, separated by an interval of 6 min. Exertion at this workload induced arterial hypoxemia within 30 s of the onset of galloping as well as desaturation of Hb, a progressive rise in arterial PCO2, and acidosis as exercise duration increased from 30 to 120 s. In the single-exercise-bout experiments, blood-gas/pH data resembled those from the first run of the double-exercise experiments, and all horses experienced EIPH. Thus, in the double-exercise experiments, before the horses performed the second bout of galloping at 14 m/s on a 3.5% uphill grade, stress failure of pulmonary capillaries had occurred. Although arterial hypoxemia developed during the second run, arterial PO2 values were significantly (P < 0.01) higher than in the first run. Thus prior exercise not only failed to accentuate the severity of arterial hypoxemia, it actually diminished the magnitude of exercise-induced arterial hypoxemia. The decreased severity of exercise-induced arterial hypoxemia in the second run was due to an associated increase in alveolar PO2, as arterial PCO2 was significantly lower than in the first run. Thus our data do not support a role for structural changes in the blood-gas barrier related to the stress failure of pulmonary capillaries in causing the exercise-induced arterial hypoxemia in horses.     

Effect of platelet-activating factor-receptor antagonism on endotoxin-induced lung dysfunction in sheep

To further define the role ofplatelet-activating factor (PAF) in endotoxin-induced lung dysfunction,we examined the effect of ABT-299, a specific and potent PAF-receptorantagonist, on the response to endotoxemia in six chronicallyinstrumented awake sheep. We administered Escherichiacoli endotoxin (0.5 µg/kg) intravenously with orwithout pretreatment with ABT-299 while monitoring mean pulmonaryarterial pressure (Ppa), mean systemic arterial pressure (Psa), dynamiccompliance of the lungs (Cdyn), and functional residual capacity (FRC).Endotoxin administration caused pulmonary hypertension, reduced Cdyn,leukopenia, and hypoxemia while having no significant effect on Psa orFRC. Administration of ABT-299 did not affect any of the measuredvariables at baseline. Pretreatment with ABT-299 attenuated the peakPpa seen after endotoxin administration but had minimal effects onendotoxin-induced changes in Cdyn, white blood cell count, oralveolar-to-arterial oxygen difference. ABT-299 was shown to completelyblock the pulmonary hypertension and reduction in Cdyn seen afterintravenous administration of exogenous PAF. We conclude that PAF doesnot play an essential role in the sheep's response to endotoxin.

     

NO inhalation reduces pulmonary arterial pressure but not hemorrhage in maximally exercising horses.

In horses, the exercise-induced elevation of pulmonary arterial pressure (Ppa) is thought to play a deterministic role in exercise-induced pulmonary hemorrhage (EIPH), and thus treatment designed to lower Ppa might reasonably be expected to reduce EIPH. Five Thoroughbred horses were run on a treadmill to volitional fatigue (incremental step test) under nitric oxide (NO; inhaled 80 ppm) and control (N(2), same flow rate as per NO run) conditions (2 wk between trials; order randomized) to test the hypothesis that NO inhalation would reduce maximal Ppa but that this reduction may not necessarily reduce EIPH. Before each investigation, a microtipped pressure transducer was placed in the pulmonary artery 8 cm past the pulmonic valve to monitor Ppa. EIPH severity was assessed via bronchoalveolar lavage (BAL) 30 min postrun. Exercise time did not differ between the two trials (P > 0.05). NO administration resulted in a small but consistent and significant reduction in peak Ppa (N(2), 102.3 +/- 4.4; NO, 98.6 +/- 4.3 mmHg, P < 0.05). In the face of lowered Ppa, EIPH severity was significantly higher in the NO trial (N(2), 22.4 +/- 6.8; NO, 42.6 +/- 15.4 x 10(6) red blood cells/ml BAL fluid, P < 0.05). These findings support the notion that extremely high Ppa may reflect, in part, an arteriolar vasoconstriction that serves to protect the capillary bed from the extraordinarily high Ppa evoked during maximal exercise in the Thoroughbred horse. Furthermore, these data suggest that exogenous NO treatment during exercise in horses may not only be poor prophylaxis but may actually exacerbate the severity of EIPH.     

Modulation of pulmonary arterial input impedance during transition from inspiration to expiration

Castiglioni, P., R. Tommasini, M. Morpurgo, and M. DiRienzo. Modulation of pulmonary arterial input impedance during transition from inspiration to expiration. J. Appl.Physiol. 83(6): 2123-2130, 1997.We investigatedwhether respiration influences pulmonary arterial input impedanceduring transition from inspiration to expiration in five anesthetized,spontaneously breathing dogs. Impedance (Z) was separately assessed forheart beats occurring in inspiration, in expiration, and during thetransition from inspiration to expiration (transitional beat).Transitional beats were scored by the ratio between the fraction ofbeat falling in expiration and the total beat duration[expiratory fraction (E_fr)] to quantify theirposition within the transition. In transitional beats, input resistancelinearly increased with E_fr; Zmodulus at the heart-rate frequency(f_HR) decreased up to50% for E_fr = 50%. Z phase at f_HR was greaterthan in inspiration for E_fr <40% and lower for E_fr >50%.Unlike blood flow velocity, mean value and first harmonic of pulmonaryarterial pressure were correlated toE_fr and paralleled the changes ofinput resistance and Z at f_HR.This indicates that respiration influences Z through modifications inarterial pressure. The evidence of important respiratory influences onZ function may help the pathophysiological interpretation of dysfunctions of the right heart pumping action, such as the so-called cor pulmonale.

     

Systemic and pulmonary hemodynamic responses to normal and obstructed breathing during sleep

Schneider, H., C. D. Schaub, K. A. Andreoni, A. R. Schwartz,R. L. Smith, J. L. Robotham, and C. P. O'Donnell. Systemic andpulmonary hemodynamic responses to normal and obstructed breathing during sleep. J. Appl. Physiol. 83(5):1671-1680, 1997.We examined the hemodynamic responses to normalbreathing and induced upper airway obstructions during sleep in acanine model of obstructive sleep apnea. During normal breathing,cardiac output decreased (12.9 ± 3.5%,P < 0.025) from wakefulness tonon-rapid-eye-movement sleep (NREM) but did not change from NREM torapid-eye-movement (REM) sleep. There was a decrease(P < 0.05) in systemic (7.2 ± 2.1 mmHg) and pulmonary (2.0 ± 0.6 mmHg) arterial pressures fromwakefulness to NREM sleep. In contrast, systemic (8.1 ± 1.0 mmHg,P < 0.025), but not pulmonary,arterial pressures decreased from NREM to REM sleep. During repetitiveairway obstructions (56.0 ± 4.7 events/h) in NREM sleep, cardiacoutput (17.9 ± 3.1%) and heart rate (16.2 ± 2.5%) increased(P < 0.05), without a change instroke volume, compared with normal breathing during NREM sleep. Duringsingle obstructive events, left (7.8 ± 3.0%,P < 0.05) and right (7.1 ± 0.7%, P < 0.01)ventricular outputs decreased during the apneic period. However, left(20.7 ± 1.6%, P < 0.01) andright (24.0 ± 4.2%, P < 0.05)ventricular outputs increased in the postapneic period because of anincrease in heart rate. Thus 1) thesystemic, but not the pulmonary, circulation vasodilates during REMsleep with normal breathing; 2)heart rate, rather than stroke volume, is the dominant factormodulating ventricular output in response to apnea; and3) left and right ventricular outputs oscillate markedly and in phase throughout the apnea cycle.

     

Nitric oxide decreases lung liquid production in fetal lambs

Cummings, James J. Nitric oxide decreases lung liquidproduction in fetal lambs. J. Appl.Physiol. 83(5): 1538-1544, 1997.To examine theeffect of nitric oxide on fetal lung liquid production, I measured lungliquid production in fetal sheep at 130 ± 5 days gestation (range122-137 days) before and after intrapulmonary instillation ofnitric oxide. Thirty-one studies were done in which net lung luminalliquid production (Jv) was measured by plotting the change in lung luminal liquid concentration ofradiolabeled albumin, an impermeant tracer that was mixed into the lungliquid at the start of each study. To see whether changes inJvmight be associated with changes in pulmonary hemodynamics, pulmonary and systemic pressures were measured and left pulmonary arterial flowwas measured by an ultrasonic Doppler flow probe. Variables weremeasured during a 1- to 2-h control period and for 4 h after a smallbolus of isotonic saline saturated with nitric oxide gas (10 or 100%)was instilled into the lung liquid. Control (saline) instillations(n = 6) caused no change in anyvariable over 6 h. Nitric oxide instillation significantly decreasedJv and increased pulmonary blood flow;these effects were sustained for 1-2 h. There was also asignificant but transient decrease in pulmonary arterial pressure. Thusintrapulmonary nitric oxide causes a significant decrease in lungliquid and is associated with a decrease in pulmonary vascularresistance. In a separate series of experiments either amiloride orbenzamil, which blocks Na⁺transport, was mixed into the lung liquid before nitric oxide instillation; still, there was a similar reduction in lung liquid production. Thus the reduction in lung liquid secretion caused bynitric oxide does not appear to depend on apicalNa⁺ efflux.

     

Nitric oxide-endothelin-1 interaction in humans

Ahlborg, Gunvor, and Jan M. Lundberg. Nitricoxide-endothelin-1 interaction in humans. J. Appl.Physiol. 82(5): 1593-1600, 1997.Healthy menreceived N^G-monomethyl-L-arginine(L-NMMA) intravenously to studycardiovascular and metabolic effects of nitric oxide synthase blockadeand whether this alters the response to endothelin-1 (ET-1) infusion.Controls only received ET-1.L-NMMA effects were that heartrate (17%), cardiac output (17%), and splanchnic and renal blood flow(both 33%) fell promptly (all P < 0.01). Mean arterial blood pressure (6%), and systemic (28%) andpulmonary (40%) vascular resistances increased(P < 0.05 to 0.001). Arterial ET-1levels (21%) increased due to a pulmonary net ET-1 release(P < 0.05 to 0.01). Splanchnic glucose output (SGO) fell (26%, P < 0.01). Arterial insulin and glucagon were unchanged. Subsequent ET-1infusion caused no change in mean arterial pressure, heart rate, orcardiac output, as found in the present controls, or in splanchnic andrenal blood flow or splanchnic glucose output as previously found withET-1 infusion (G. Ahlborg, E. Weitzberg, and J. M. Lundberg.J. Appl. Physiol. 79: 141-145,1995). In conclusion, L-NMMAlike ET-1, induces prolonged cardiovascular effects and suppresses SGO.L-NMMA causes pulmonary ET-1release and blocks responses to ET-1 infusion. The results indicatethat nitric oxide inhibits ET-1 production and thereby interacts withET-1 regarding increase in vascular tone and reduction of SGO inhumans.

     

Pulse pressure response to the strain of the Valsalva maneuver in humans with preserved systolic function

Arterial pulsepressure response during the strain phase of the Valsalva maneuver hasbeen proposed as a clinical tool for the diagnosis of left heartfailure, whereas responses of subjects with preserved systolic functionhave been poorly documented. We studied the relationship between theaortic pulse amplitude ratio (i.e., minimum/maximum pulse pressure)during the strain phase of the Valsalva maneuver and cardiachemodynamics at baseline in 20 adults (42 ± 14 yr) undergoingroutine right and left heart catheterization. They were normal subjects(n = 5) and patients withvarious forms of cardiac diseases(n = 15), and all had a leftventricular ejection fraction 40%. High-fidelity pressures wererecorded in the right atrium and the left ventricle at baseline and atthe aortic root throughout the Valsalva maneuver. Aortic pulseamplitude ratio 1) did not correlatewith baseline left ventricular end-diastolic pressure, cardiac index(thermodilution), or left ventricular ejection fraction(cineangiography) and 2) waspositively related to total arterial compliance (area method) (r = 0.59) and to basal mean rightatrial pressure (r = 0.57) (eachP < 0.01). Aortic pulse pressureresponses to the strain were not related to heart rate responses duringthe maneuver. In subjects with preserved systolic function, the aorticpulse amplitude ratio during the strain phase of the Valsalva maneuver relates to baseline total arterial compliance and right heart fillingpressures but not to left ventricular function.

     

Effects of transient intrathoracic pressure changes (hiccups) on systemic arterial pressure

Mathew, Oommen P. Effects of transient intrathoracicpressure changes (hiccups) on systemic arterial pressure.J. Appl. Physiol. 83(2): 371-375, 1997.The purpose of the study was to determine the effect oftransient changes in intrathoracic pressure on systemic arterialpressure by utilizing hiccups as a tool. Values of systolic anddiastolic pressures before, during, and after hiccups were determinedin 10 intubated preterm infants. Early-systolic hiccups decreasedsystolic blood pressure significantly (P < 0.05) compared with control(39.38 ± 2.72 vs. 46.46 ± 3.41 mmHg) and posthiccups values,whereas no significant change in systolic blood pressure occurredduring late-systolic hiccups. Diastolic pressure immediately after thehiccups remained unchanged during both early- and late-systolichiccups. In contrast, diastolic pressure decreased significantly(P < 0.05) when hiccups occurred during diastole (both early and late). Systolic pressures of the succeeding cardiac cycle remained unchanged after early-diastolic hiccups, whereas they decreased after late-diastolic hiccups. Theseresults indicate that transient decreases in intrathoracic pressurereduce systemic arterial pressure primarily through an increase in thevolume of the thoracic aorta. A reduction in stroke volume appears tocontribute to the reduction in systolic pressure.

     

Blood flow vs. venous pressure effects on filtration coefficient in oleic acid-injured lung

On the basis ofchanges in capillary filtration coefficient(K_fc) in 24 rabbit lungs, we determined whether elevations in pulmonary venouspressure (Ppv) or blood flow (BF) produced differences infiltration surface area in oleic acid-injured (OA) or control (Con)lungs. Lungs were cyclically ventilated and perfused under zone 3 conditions by using blood and 5% albumin with no pharmacological modulation of vascular tone. Pulmonary arterial, venous, and capillary pressures were measured by using arterial, venous, and double occlusion. Before and during eachK_fc-measurementmaneuver, microvascular/total vascular compliance was measured by usingvenous occlusion.K_fc was measuredbefore and 30 min after injury, by using a Ppv elevation of 7 cmH₂O or a BF elevation from 1 to2 l · min¹ · 100 g¹ to obtain a similardouble occlusion pressure. Pulmonary arterial pressure increased morewith BF than with Ppv in both Con and OA lungs [29 ± 2 vs. 19 ± 0.7 (means ± SE) cmH₂O;P < 0.001]. In OA lungscompared with Con lungs, values ofK_fc (200 ± 40 vs. 83 ± 14%, respectively; P < 0.01) and microvascular/total vascular compliance ratio (86 ± 4 vs. 68 ± 5%, respectively; P < 0.01) increased more with BF than with Ppv. In conclusion, for a given OA-induced increase in hydraulic conductivity, BF elevation increased filtration surface area more than did Ppv elevation. The steep pulmonary pressure profile induced by increased BF could result in therecruitment of injured capillaries and could also shift downstream thecompression point of blind (zone 1) and open injured vessels (zone 2).

     

Circulatory effects of prolonged hypoxia before and during antihistamine.

Five chronically instrumented healthy dogs were exposed to a 5-day period of breathing 10% oxygen in a chamber. The response to hypoxia was found to be time dependent. During the first 24 h of hypoxia the circulatory response was characterized by increases in cardiac output, heart rate, pulmonary and systemic arterial blood pressures, and pulmonary vascular resistance. Systemic vascular resistance increased; left atrial pressure decreased. During the early part of hypoxia the animals became hypocapnic; the arterial blood pH rose significantly. During the rest of the hypoxic period cardiac output, heart rate, and arterial blood pH returned to the control values; pulmonary and systemic arterial pressures and pulmonary vascular resistance remained significantly elevated. Systemic vascular resistance rose; left atrial pressure remained below control. This response to hypoxia was not substantially modified when the experiment was repeated during the administration of the antihistamine promethazine, an H1-receptor blocking agent, in a dose which blocked the pulmonary vasoconstrictor response to small doses of exogenous histamine. The circulatory response to acute hypoxia in five anesthetized dogs was not modified by intravenous administration of metiamide, an H2-receptor blocking agent.     

Efficacy of nasal strip and furosemide in mitigating EIPH in Thoroughbred horses.

The purpose of this investigation was to study the effects of an equine nasal strip (NS), furosemide (Fur), and a combination of both (NS + Fur) on exercise-induced pulmonary hemorrhage (EIPH) at speeds corresponding to near-maximal effort. Five Thoroughbreds (526 +/- 25 kg) were run on a flat treadmill from 7 to 14 m/s in 1 m x s(-1) x min(-)1 increments every 2 wk (treatment order randomized) under control (Con), Fur (1 mg/kg iv 4 h prior), NS, or NS + Fur conditions. During each run, pulmonary arterial (Ppa) and esophageal (Pes) pressures were measured. Severity of EIPH was quantified via bronchoalveolar lavage (BAL) 30 min postrun. Furosemide (Fur and NS + Fur trials) reduced peak Ppa approximately 7 mmHg compared with Con (P < 0.05) whereas NS had no effect (P > 0.05). Maximal Pes swings were not different among groups (P > 0.05). NS significantly diminished EIPH compared with the Con trial [Con, 55.0 +/- 36.2; NS, 30.8 +/- 21.8 x 10(6) red blood cells (RBC)/ml BAL fluid; P < 0.05]. Fur reduced EIPH to a greater extent than NS (5.2 +/- 3.0 x 10(6) RBC/ml BAL; P < 0.05 vs. Con and NS) with no additional benefit from NS + Fur (8.5 +/- 4.2 x 10(6) RBC/ml BAL; P > 0.05 vs. Fur, P < 0.05 vs. Con and NS). In conclusion, although both modalities (NS and Fur) were successful in mitigating EIPH, neither abolished EIPH fully as evaluated via BAL. Fur was more effective than NS in constraining the severity of EIPH. The simultaneous use of both interventions appears to offer no further gain with respect to reducing EIPH.     

Bedside determination of left atrial pressure

An investigation was conducted to assess the accuracy of left heart filling pressures determined by a right heart catheter introduced at the bedside. Twelve patients were studied after open cardiac surgery by simultaneously recording pressures from both sides of the pulmonary capillary bed with a direct left atrial catheter and a flow-directed pulmonary arterial catheter. The mean pulmonary artery “occluded” pressure was shown to be a highly reliable index of mean left atrial pressure in all cases. It was much more accurate than pulmonary end-diastolic pressure, especially in six patients with pre-existing pulmonary hypertension.     

Water transport and the distribution of aquaporin-1 in pulmonary air spaces

Effros, R. M., C. Darin, E. R. Jacobs, R. A. Rogers, G. Krenz, and E. E. Schneeberger. Water transport and thedistribution of aquaporin-1 in pulmonary air spaces.J. Appl. Physiol. 83(3): 1002-1016, 1997.Recent evidence suggests that water transport between the pulmonary vasculature and air spaces can be inhibited byHgCl₂, an agent that inhibitswater channels (aquaporin-1 and -5) of cell membranes. In the presentstudy of isolated rat lungs, clearances of labeled(³HOH) and unlabeled water werecompared after instillation of hypotonic or hypertonic solutions intothe air spaces or injection of a hypotonic bolus into the pulmonaryartery. The clearance of ³HOHbetween the air spaces and perfusate after intratracheal instillation and from the vasculature to the tissues after pulmonary arterial injections was invariably greater than that of unlabeled water, indicating that osmotically driven transport of water is limited bypermeability of the tissue barriers rather than the rate of perfusion.Exposure to 0.5 mM HgCl₂ in theperfusate and air-space solution reduced the product of the filtrationcoefficient and surface area(P_fS)of water from the air spaces to the perfusate by 28% afterinstillation of water into the trachea. In contrast, perfusion of 0.5 mM HgCl₂ in air-filled lungs reducedP_fSof the endothelium by 86% after injections into the pulmonary artery, suggesting that much of the action of this inhibitor is on the endothelial surfaces. Confocal laser scanning microscopy demonstrated that aquaporin-1 is on mouse pulmonary endothelium. No aquaporin-1 wasfound on alveolar type I cells with immunogold transmission electronmicroscopy, but small amounts were present on some type II cells.

     

Morphometry of the human pulmonary vasculature

Huang, W., R. T. Yen, M. McLaurine, and G. Bledsoe.Morphometry of the human pulmonary vasculature.J. Appl. Physiol. 81(5):2123-2133, 1996.The morphometric data on the branching patternand vascular geometry of the human pulmonary arterial and venous treesare presented. Arterial and venous casts were prepared by the siliconeelastomer casting method. Three recent innovations are used to describethe vascular geometry: the diameter-defined Strahler ordering model isused to assign branching orders, the connectivity matrix is used todescribe the connection of blood vessels from one order to another, anda distinction between vessel segments and vessel elements is used toexpress the series-parallel feature of the pulmonary vessels. A totalof 15 orders of arteries were found between the main pulmonary arteryand the capillaries in the left lung and a total of 15 orders of veinsbetween the capillaries and the left atrium in the right lung. Theelemental and segmental data are presented. The morphometric data arethen used to compute the total cross-sectional areas, blood volumes, and fractal dimensions in the pulmonary arterial and venous trees.

     

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.