Distribution Of Pulmonary Vascular Resistance Research Articles

Species differences in pulmonary vasoactive responses to histamine, 5-hydroxytryptamine, and KCl

Species differences in the longitudinal distribution of pulmonary vascular resistance (PVR) in response to 5-hydroxytryptamine (5-HT) or histamine (His) may be attributed to variations in the distribution of functional smooth muscle between arteries and veins estimated by the response to KCl. Isolated dog, guinea pig, or rabbit lungs were perfused at a constant flow = 55-75 ml.min-1.kg body wt-1. Pulmonary arterial (Ppa); arterial, double, and venous occlusion (Po,a; Pdo; Po,v, respectively); and pulmonary venous (Ppv) pressures were measured before and after increasing PVR by infusing His, 5-HT, or KCl. 5-HT and His increased Ppa--Pdo in rabbits but Pdo--Ppv in guinea pigs. In dogs, 5-HT increased Ppa--Po,a, but His increased Pdo--Ppv. Dynamic (Co,v) and static vascular compliance (CP-Q), as well as critical closing pressure (Pcc, the gamma-intercept of pressure-flow curves), were also measured. At baseline, Co,v was the same among species. However, CP-Q was higher than Co,v in all lungs and was significantly different among species in order of (in ml.cmH2O-1.100 g-1) rabbit (4.54 +/- 0.28) > guinea pig (3.31 +/- 0.18) > dog (2.21 +/- 0.13). Increases in Pcc correlated with increases in microvascular resistance (Po,a--Po,v) but not with increases in PVR after agonist infusion. KCl responses suggest that guinea pigs and rabbits have relatively more functional smooth muscle in venous and arterial microvessels, respectively, whereas dogs have approximately equal amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

The pulmonary circulation

Recent studies have emphasized the complex regulation of the pulmonary circulation. This increased understanding should result in new therapeutic approaches in the treatment of hypoxia and pulmonary hypertension. This review will discuss some of the recent advances in our understanding of the pulmonary circulation. The effects of anesthetics on the pulmonary circulation are reviewed, emphasizing the multiple modulatory systems which are altered by specific anesthetic agents. The therapeutic role of inhaled nitric oxide, and the modulatory role of endogenous nitric oxide, on the pulmonary circulation are discussed. New insights into the mechanism of hypoxic pulmonary vasoconstriction (HPV) are presented. Clinical advances in the epidemiology of pulmonary hypertension, the use of vasodilators, the role of single lung transplantation, and the anesthetic management of pulmonary hypertension are discussed. Pulmonary capillary pressure (PCP) and its dependence on the longitudinal distribution of pulmonary vascular resistance are reviewed. Finally, the role of the pulmonary circulation in acute lung injury is emphasized.

K+ATP-channel activation causes marked vasodilation in the hypertensive neonatal pig lung.

We studied the potential role of ATP-sensitive potassium (K+ATP) channel activation in mediating pulmonary vasodilation in newborn piglets. Piglet lungs (n = 14, ages 1-4 days) were artificially perfused with recirculating Ringer solution containing bovine serum albumin and statistically inflated using 95% O2-5% CO2. We measured pulmonary arterial pressure (Ppa) and distribution of pulmonary vascular resistance (using double-occlusion method). Under resting conditions (Ppa 13.7 +/- 1.6 cmH2O, mean +/- SE), the K+ATP channel agonist BRL 38227 (lemakalim, 10(-7) and 10(-6) M) caused small dose-dependent pulmonary vasodilation. This response was diminished by the K+ATP-channel blocker glibenclamide (10(-5) M). Pretreatment of lungs with indomethacin (10(-5) M) and N omega-nitro-L-arginine (10(-5) M) to inhibit cyclooxygenase- and nitric oxide (NO)-related vasodilation, respectively, resulted in a marked increase in the baseline Ppa to 85.6 +/- 11.2 cmH2O. Injection of BRL 38227 (10(-7) M and 10(-6) M) in these lungs decreased Ppa to 72.5 +/- 8.5 (P < 0.01) and 19.3 +/- 0.9 cmH2O (P < 0.01), respectively; the corresponding times for half-recovery of Ppa (t1/2R) were 5.7 +/- 4.3 and > 20 min. Glibenclamide (10(-5) M) abolished the response to 10(-7) M BRL 38227 and significantly diminished (P < 0.05) the decreases in Ppa and t1/2R in response to 10(-6) M BRL 38227 but not to acetylcholine (10(-10) M). We conclude that activation of K+ATP channels has a minimal role in maintaining basal pulmonary vasomotor tone but is able to induce marked vasodilation when NO and cyclooxygenase-dependent vasodilatory mechanisms are inhibited.

Pulmonary capillary pressure: a review.

To demonstrate the importance of a) measuring effective pulmonary capillary pressure and b) evaluating the longitudinal distribution of pulmonary vascular resistance relative to pre- and postcapillary resistances. To review the development of methods used to determine pulmonary capillary pressure in experimental animal and clinical studies. Human, animal, and modeling studies published since 1966 identified through MEDLINE and a review of bibliographies of relevant articles. All studies identified were reviewed with an emphasis on recent studies and those studies identifying various methodologies used to determine capillary pressure. Experimental studies were selected for their historical value and applicability to the clinical setting. Different models of the pulmonary circulation have been proposed. The electrical circuit model, which incorporated capacitance elements and two or four resistive elements, has been the basis for the determination of pulmonary capillary pressure in isolated lungs and in situ lungs in animals and patients. Methods used to determine pulmonary capillary pressure from a pulmonary arterial pressure tracing after balloon occlusion are: a) division of waveform into two components and logarithmic extrapolation of the slow component to occlusion time; b) visual determination of the pressure inflection point of the pulmonary arterial pressure tracing; and c) computer processing of the total arterial pressure transient. Both ease of calculations and difficulties can arise when each method is used. Pulmonary capillary hydrostatic pressure is an important determinant of pulmonary edema especially in the setting of pulmonary hypertension and adult respiratory distress syndrome. Hypoxia, sepsis, cardiac valvular disease, and inflammatory mediators produce variable changes in the longitudinal distribution of pulmonary vascular resistance so that an increased capillary pressure cannot be predicted by the pulmonary arterial or occlusion pressure. For proper therapy aimed at decreasing pulmonary vascular resistance, it is important to determine whether or not the particular therapy increases capillary pressure. Pulmonary capillary pressure is the most important determinant of lung fluid balance and is the major physiologic parameter that should be measured when various forms of plasma volume expansion and pulmonary vasodilators are used in the critically ill patient.

Longitudinal distribution of pulmonary vascular resistance after endotoxin administration in sheep

Pulmonary hypertension may increase pulmonary capillary pressure and exacerbate pulmonary edema in acute respiratory failure. The effects of pulmonary hypertension on pulmonary capillary pressure depend on the longitudinal distribution of pulmonary vascular resistance. Since pulmonary hypertension occurs during acute respiratory failure, we hypothesized that acute respiratory failure may produce time-dependent changes in the longitudinal distribution of pulmonary vascular resistance. Therefore, we measured pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in an animal model of acute respiratory failure. Escherichia coli endotoxin (2.5 to 5.0 micrograms/kg) was administered over a 1-hr period in eight anesthetized sheep. Pulmonary and systemic hemodynamics, including pulmonary artery occlusion pressure (PAOP), pulmonary capillary pressure, and the longitudinal distribution of pulmonary vascular resistance, were measured over the next 5 hrs. Pulmonary capillary pressure was estimated by analysis of the pressure decay following pulmonary artery balloon inflation. Endotoxin administration resulted in sustained pulmonary hypertension for the subsequent 5 hrs of the study. Pulmonary capillary pressure was increased 7 mm Hg above baseline at 0.5 and 0.75 hrs during the infusion of endotoxin but returned to baseline values at 1.5 hrs. Despite sustained pulmonary hypertension, pulmonary capillary pressure remained at baseline values for the duration of the study. Similar to pulmonary capillary pressure, pulmonary venous (or postcapillary) resistance was increased approximately four-fold over baseline at 0.5 and 0.75 hrs after initiating endotoxin administration, but returned to baseline values by the end of endotoxin administration and remained at baseline values throughout the remainder of the study. In contrast, pulmonary arterial (or precapillary) resistance remained at values approximately three times baseline during the infusion and throughout the duration of the study. In this experimental model of acute respiratory failure, the effects of endotoxin on the longitudinal distribution of pulmonary vascular resistance are time-dependent. If these data from animals can be extrapolated to humans, we speculate that the importance of pulmonary venoconstriction in exacerbating pulmonary edema may vary over time in patients with acute respiratory failure.

Effects of Prostaglandin E1 and Hydralazine on the Longitudinal Distribution of Pulmonary Vascular Resistance during Vasoconstrictor Pulmonary Hypertension in Sheep

Pulmonary capillary pressure (Ppc) is dependent upon left atrial pressure, pulmonary venous resistance, and cardiac output. The effects of pulmonary vasodilators on Ppc will therefore depend upon any alterations in the longitudinal distribution of pulmonary vascular resistance (precapillary [arterial] and postcapillary [venous] components). We therefore studied the effects of two pulmonary vasodilators (prostaglandin E1 and hydralazine) on Ppc and the longitudinal distribution of pulmonary vascular resistance. Pulmonary hypertension was produced in sheep by the continuous administration of the thromboxane A2-mimetic U46619. Ppc was measured by analysis of pulmonary artery occlusion pressure decay curves. U46619 increased Ppc by 9 mmHg and increased both the arterial and venous components of pulmonary vascular resistance. Subsequent administration of prostaglandin E1 decreased Ppc by 5 mmHg and decreased both the arterial and venous components of pulmonary vascular resistance (by 50 and 69% respectively). Hydralazine produced smaller decreases in the arterial and venous components of pulmonary vascular resistance (by 35 and 49% respectively) and did not significantly reduce Ppc. We conclude that prostaglandin E1 but not hydralazine is effective in decreasing Ppc in this experimental model of pulmonary hypertension.

Derived pulmonary capillary pressure changes after smoke inhalation in sheep

We determined derived pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance in chronically instrumented sheep with inhalation injury by using analysis of pressure decay curves after pulmonary artery occlusion. There was an increase in derived pulmonary capillary pressure and an increase in the lung lymph flow after smoke inhalation. The pulmonary vascular, arterial, and venous resistances increased significantly in the inhalation group. Pulmonary venous resistance increased proportionately more than pulmonary arterial resistance in the inhalation group. The plasma osmotic pressure-derived pulmonary capillary pressure gradient decreased to a greater extent in the inhalation group than in the control group. The present experiments suggest that the estimates of derived pulmonary capillary pressure can predict filtration pressure better than pulmonary artery occlusion pressure. The derived pulmonary capillary pressure can be measured easily in man with a pulmonary arterial catheter.

Mechanism of endothelin-1-induced pulmonary vasoconstriction.

Endothelins are endothelial cell-derived peptides with potent vasoconstrictor properties. We investigated the actions of porcine/human endothelin-1 (ET-1) on the microvasculature of the guinea pig lung perfused at constant flow with Ringers-albumin. We measured the perfusion pressure, distribution of pulmonary vascular resistance (using the double occlusion method), lung weight change, and the pulmonary capillary filtration coefficient. At concentrations of greater than or equal to 10(-10) M, ET-1 produced dose-dependent increases in mean pulmonary artery pressure (EC50, approximately 10(-9.5) M), which were rapid in onset and biphasic (first phase peaking at 1-2 minutes; second phase peaking at 10-15 minutes) up to 60 minutes of the perfusion period. The vasoconstrictor response was sustained for the 60-minute perfusion period. The pulmonary vasoconstriction was inhibited by pretreatment with indomethacin (10(-5) M), the thromboxane A2 receptor antagonist SQ-29,548 (4 x 10(-6) M), or papaverine (10(-5) M). Nifedipine (10(-5) or 10(-7) M) had no effect on the first phase but prevented the second phase of the vasoconstriction. The vasoconstriction was primarily the result of a 10-fold increase in pulmonary venous resistance. Pulmonary edema developed after ET-1 challenge because of the venoconstriction and the resultant pulmonary capillary hypertension. However, the pulmonary capillary filtration coefficient was unchanged, indicating that pulmonary vascular permeability did not increase. ET-1 also had no effect on transendothelial 125I-albumin flux. The results indicate that ET-1 is a potent thromboxane-dependent venoconstrictor in the guinea pig lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary capillary pressure and gas exchange after E. coli bacteremia in pigs

In 9 Goettingen minipigs we studied the effect of E. coli bacteremia on effective pulmonary capillary pressure and the longitudinal distribution of pulmonary vascular resistance. Precapillary pressure gradient (dPa) was calculated as the difference between mean pulmonary artery pressure (MPP) and effective pulmonary capillary pressure (Pc) (dPa = MPP-Pc), postcapillary pressure gradient (dPv) as the difference between Pc and left atrial pressure (dPv = Pc-LAP). The disturbance of pulmonary gas exchange was quantified by the AaDO2 quotient 1-PaO2/PAO2. Live E. coli infusion resulted in hypodynamic circulatory failure. Cardiac index fell from 3.7 +/- 0.81 . min-1.m-2 to 2.2 +/- 0.71 .min-1.m-2 after bacteremia lasting for 3.5 h. Simultaneously venous pulmonary vascular resistance rose from 25% of total pulmonary vascular resistance before to 32% after 3.5 h bacteremia, thus raising Pc from 11 mmHg to 16 mmHg. The degree of respiratory insufficiency was correlated with changes of MPP, dPa and dPv: 1-PaO2/PAO2 = 0.2 + 0.035.dPv (r = 0.829). Our results show, that the longitudinal distribution of pulmonary vascular resistance changes during septicemia, thus raising Pc. This may be an important factor in the genesis of septic pulmonary failure.

Distribution of pulmonary vascular resistance during lactic acid infusion in dogs

We sought to determine the longitudinal distribution of pulmonary vascular resistance (PVR) in acute lactic acidosis utilizing pulmonary artery and vein balloon occlusion techniques (Holloway et al. J. Appl. Physiol. 54: 840-851, 1983). In anesthetized dogs, both a systemic vein (I-V) infusion and systemic artery (I-A) infusion of L-lactic acid were studied to control for potential effects of factors other than pH on PVR. During progressive I-A infusion (n = 9) to a pH of 6.94 +/- 0.06 there was no significant change in PVR or its distribution. In contrast, I-V infusion (n = 9) to a pH of 7.08 +/- 0.09 increased median PVR from 3.6 to 21.7 mmHg.1(-1).min (P less than 0.001), due to an increase in middle segment resistance (0.0-15.4 mmHg.1(-1).min, P less than 0.02). Examination by light and electron microscopy demonstrated pulmonary capillary obstruction with hemolyzed erythrocyte (RBC) membranes with I-V infusion, but representative I-A animals did not demonstrate these findings. Conceivably, the systemic vascular bed filtered the fragmented RBC membranes in the I-A model, but this microvascular obstruction with altered RBCs and RBC fragments caused the pulmonary hypertension observed in the I-V infusion. We conclude that lactic acidosis does not increase pulmonary vascular tone in dogs, a finding compatible with most previous studies in which observed increases in PVR may be attributed to other effects from I-V acid infusion on circulating blood elements.

Distribution of pulmonary vascular pressure as a function of perinatal age in lambs.

The distribution of pulmonary vascular resistance (PVR) with respect to compliance was determined using vascular occlusion in isolated lungs from lambs at five ages, from 2 wk before birth to 1 mo of age. The major change in PVR occurred in the pressure gradient across the middle compliant region (delta Pm), which dropped sharply at birth, remained low for 2 wk, and increased at 1 mo. Pulmonary vasoreactivity also varied with ages. Lungs at 0-4 days did not respond to hypoxia and responded poorly to prostaglandin F2 alpha (PGF2 alpha). In contrast, lungs at 13-33 days had significant increases in delta Pm and the gradient across relatively indistensible arterial vessels during hypoxia and increases in all gradients with PGF2 alpha. Ventilation of fetal lungs reduced PVR, mainly because of a 50% reduction in delta Pm. Our results demonstrate that the magnitude and distribution of PVR relative to compliance varied as a function of perinatal age and that pulmonary vasoreactivity depended on postnatal age. The major effect of ventilating fetal lungs was on the middle region.

Distribution of pulmonary vascular resistance in experimental fibrosis

To elucidate mechanisms of pulmonary hypertension in interstitial fibrosis, we compared the left lower lobes (LLL) of six dogs in which fibrosis was induced by radiation and bleomycin with the normal right lower lobes (RLL) for 1) slope and intercept of the vascular pressure-flow (P-Q) curves, 2) segmental resistances with arterial and venous occlusion under base-line conditions, after serotonin and vasodilators, and 3) light-microscopic morphology and morphometry. We found that 1) the total volume and vascular compliance of the fibrotic LLL were five and four times less, respectively, than controls, 2) the slope and intercept of the P-Q curves in the LLL were 154.0 +/- 65.8 (SE) mmHg.l-1.min-1 and 8.2 +/- 1.5 mmHg, respectively, compared with 18.3 +/- 2.3 and 3.2 +/- 0.9 for the RLL, 3) the resistance of the arterial, middle, and venous segments in the LLL were higher than in the RLL, but middle segment resistance rose disproportionately, and 4) constriction of the arterial segment with serotonin was similar in LLL and RLL, and vasodilators were ineffective. Histologically, fibrosis involved 36% of the lung, and the capillary bed was severely obliterated. Arteries showed an increased percentage of medial and intimal thickening and peripheral muscularization; venous abnormalities were less marked. We conclude that pulmonary fibrosis increases vascular resistance mainly in the middle segment, largely by loss of tissue and obliteration of the microvasculature.

Measurement of the Longitudinal Distribution of Pulmonary Vascular Resistance from Pulmonary Artery Occlusion Pressure Profiles

Measurement of the Longitudinal Distribution of Pulmonary Vascular Resistance from Pulmonary Artery Occlusion Pressure Profiles

Bedside measurement of pulmonary capillary pressure in patients with acute respiratory failure.

In this report, the authors present the results of 34 estimates of pulmonary capillary pressure (Pcap) in 15 adult patients receiving intensive care for acute respiratory failure (ARF). Within the pulmonary artery pressure profile during transient balloon occlusion, the authors identified two exponential pressure decay components-the slower one representing the discharge of the pulmonary capillary pressure through the pulmonary venous resistance. By extrapolating this exponential to its origin at the moment of pulmonary artery occlusion, a pressure within the pulmonary vascular bed which approximates pulmonary capillary pressure (Pcap) was identified. Pcap, and not the pulmonary artery occlusion pressure (PAOP), is the major driving pressure forcing fluid from the pulmonary microvasculature. The results indicate that a discrete value for pulmonary capillary pressure can be reproducibly measured in paralyzed ventilated patients. The data report that mean pulmonary artery pressure, pulmonary capillary pressure, and total pulmonary vascular resistance (PVR) are increased in acute respiratory failure, but there is considerable variation in the distribution of pulmonary vascular resistance between the arterial and venous beds. The data suggest that there is unequal and variable partitioning of the increased PVR during acute respiratory failure. Bedside pressure profile Pcap measurements will allow optimum reduction of Pcap during ARF by infusing vasoactive agents to modify the distribution of PVR or reducing the PAOP.

Longitudinal distribution of pulmonary vascular resistance with very high pulmonary blood flow.

Dog left upper lobes (LUL) were perfused in situ via the left lower lobe artery. Lobe weight was continuously monitored. Increasing lobar flow from normal to 10 times normal had little effect on left atrial pressure, which ranged from 1 to 5 mmHg. There was a flow threshold (Qth) below which lobar weight was stable. Qth ranged from 1.1 to 1.55 l/min (mean 1.27) corresponding to four times normal LUL blood flow. Above Qth, step increases in lobar flow resulted in progressive weight gain at a constant rate that was proportional to flow. The effective pressure at the filtration site (EFP) at different flow rates was estimated from the static vascular pressure that resulted in the same rate of weight gain. From this value and from mean pulmonary arterial (PA) and left atrial (LA) pressures, we calculated resistance upstream (Rus) and downstream (Rds) from filtration site. At Qth, Rds accounted for 60% of total resistance. This fraction increased progressively with flow, reaching 83% at Q of 10 times normal. We conclude that during high pulmonary blood flow EFP is closer to PA pressure than it is to LA pressure, and that this becomes progressively more so as a function of flow. As a result, the lung accumulates water at flow rates in excess of four times normal despite a normal left atrial pressure.

Effects of Escherichia coli endotoxin on pulmonary vascular resistance in intact dogs.

The effects of endotoxin on pulmonary hemodynamics were studied in seven intact dogs. The distribution of pulmonary vascular resistance was estimated by the effective pulmonary capillary pressure, which was derived from the pressure transient recorded while the pulmonary artery catheter was rapidly wedged. After the injection of endotoxin, cardiac output and aortic pressure consistently fell. Pulmonary artery occlusion (wedge) pressure also decreased, but not significantly. Although pulmonary artery pressure did not necessarily rise, total pulmonary vascular resistance increased in every dog. The absolute increase in pulmonary artery resistance was greater (142 mm Hg/L X min/kg); than in venous resistance (111 mm Hg/L X min/kg); however, the relative increase in venous resistance was higher (410% for venous resistance vs. 220% for pulmonary artery resistance). As a result of venoconstriction, there was a consistent increase in effective pulmonary capillary pressure (from 2.5 to 6.3 mm Hg). Our data indicate that the pulmonary vascular response to endotoxin injection is characterized by constriction of both pulmonary arteries and pulmonary veins. The capillary wedge pressure did not reflect the pulmonary microvascular pressure, since it varied in the opposite direction to the effective capillary pressure.

Limits on the continuous distribution of pulmonary vascular resistance versus compliance from outflow occlusion

Rapid occlusion of the venous outflow from a lung lobe perfused with constant flow causes the arterial and venous pressure to increase with time. Pressure values obtained by linear extrapolation of the nearly linear portions of the resulting arterial and venous pressure versus time curves back to the instant of occlusion provide data which can be used to place limits on the actual unknown distribution of resistance versus compliance. This has been proven deductively for the case of compartmental models having a small number of resistances and compliances. For compartmental models having a large number of resistances and compliances approaching a continuous distribution, an inductive approach was used in which a large number of simulations indicated that the actual continuous distribution is confined by the experimental data to the same limits as those for the small number of resistances and compliances.

Lung inflation and longitudinal distribution of pulmonary vascular resistance during hypoxia.

Using the low-viscosity bolus method, we examined the influence of lung inflation on the longitudinal distribution of vascular resistance during hypoxia in isolated cat lungs. During hypoxia, increasing transpulmonary pressure decreased vascular resistance but did not change the volume into the lung at which the maximum local resistance was located. This was in contrast to the normoxic situation in which inflation caused an increase in resistance over much of the transpulmonary pressure range studied and moved the maximum local resistance downstream. These results indicate that during hypoxia the major increase in resistance was in extra-alveolar vessels and that distension of these vessels by lung inflation decreased the magnitude of the pressor response. The increase in resistance in alveolar vessels, which occurred on inflation, was similar during control and hypoxic conditions but was a smaller part of the total resistance during hypoxia because of the much larger extra-alveolar vessel resistance.

Influence of hypoxia on the longitudinal distribution of pulmonary vascular resistance.

We have examined the influence of hypoxia on the longitudinal distribution of vascular resistance and intravascular pressure in isolated cat lungs using the low-viscosity bolus technique. Hypoxia increased total vascular resistance, decreased total lung blood volume, and moved the maximum local resistance downstream away from the main pulmonary artery. The circumference of the main pulmonary artery was increased and the extravascular lung water (double indicator dilution technique) was decreased by hypoxia. Thus, it would appear that distension of the large pulmonary arteries and a decrease in the amount of lung tissue perfused contributed to the change in resistance distribution brought about by hypoxia.

Effects of lung inflation on longitudinal distribution of pulmonary vascular resistance

A low-viscosity bolus technique was employed to determine the influence of lung inflation on the distribution of pulmonary vascular resistance in isolated cat lungs. When the lungs were collapsed, the longitudinal distribution of resistance was concentrated near the proximal (arterial) part of the vascular bed. As the lungs were inflated, the resistance became more evenly distributed with the maximum located close to the midpoint of the total blood volume. The fraction of total pressure drop across the lung which occurred proximal to the midpoint of the total lung blood volume decreased from 0.69 in the collapsed lung to 0.43 at a transpulmonary pressure of 16 cmH2O.