Increase In Pulmonary Capillary Pressure Research Articles

Dynamic trend of lung fluid movement during exercise in heart failure: From lung imaging to alveolar-capillary membrane function

BackgroundIn chronic heart failure (HF), exercise-induced increase in pulmonary capillary pressure may cause an increase of pulmonary congestion, or the development of pulmonary oedema. We sought to assess in HF patients the exercise-induced intra-thoracic fluid movements, by measuring plasma brain natriuretic peptide (BNP), lung comets and lung diffusion for carbon monoxide (DLCO) and nitric oxide (DLNO), as markers of hemodynamic load changes, interstitial space and alveolar-capillary membrane fluids, respectively. Methods and resultsTwenty-four reduced ejection fraction HF patients underwent BNP, lung comets and DLCO/DLNO measurements before, at peak and 1 h after the end of a maximal cardiopulmonary exercise test. BNP significantly increased at peak from 549 (328–841) to 691 (382–1207, p < 0.0001) pg/mL and almost completely returned to baseline value 1 h after exercise. Comets number increased at peak from 9.4 ± 8.2 to 24.3 ± 16.7, returning to baseline (9.7 ± 7.4) after 1 h (p < 0.0001). DLCO did not change significantly at peak (from 18.01 ± 4.72 to 18.22 ± 4.73 mL/min/mmHg), but was significantly reduced at 1 h (16.97 ± 4.26 mL/min/mmHg) compared to both baseline (p = 0.0211) and peak (p = 0.0174). DLNO showed a not significant trend toward lower values 1 h post-exercise. ConclusionsModerate/severe HF patients have a 2-step intra-thoracic fluid movement with exercise: the first during active exercise, from the vascular space toward the interstitial space, as confirmed by comets increase, without any effect on diffusion, and the second, during recovery, toward the alveolar-capillary membrane, clearing the interstitial space but worsening gas diffusion.

Inhaled nitric oxide testing in predicting prognosis in pulmonary hypertension due to left-sided heart diseases.

The pathophysiology of pulmonary hypertension (PH) due to left-sided heart disease (Group 2 PH) is distinct from that of other groups of PH, yet there are still no approved therapies that selectively target pulmonary circulation. The increase in pulmonary capillary pressure due to left-sided heart disease is a trigger event for physical and biological alterations of the pulmonary circulation, including the nitric oxide (NO)-soluble guanylate cyclase-cyclic guanosine monophosphate axis. This study investigated inhaled NO vasoreactivity tests for patients with Group 2 PH and hypothesized that these changes may have a prognostic impact. This was a single-centre, retrospective study with a median follow-up of 365days. From January 2011 to December 2015, we studied 69 patients with Group 2 PH [age, 61.5±13.0 (standard deviation) years; male:female, 49:20; left ventricular ejection fraction, 50.1±20.4%; mean pulmonary arterial pressure, ≥25mmHg; and pulmonary arterial wedge pressure (PAWP), >15mmHg]. No adverse events were observed after NO inhalation. Thirty-four patients with Group 2 PH showed increased PAWP (ΔPAWP: 3.26±2.22mmHg), while the remaining 35 patients did not (ΔPAWP: -2.11±2.29mmHg). Multivariate analysis revealed that increased PAWP was the only significant predictor of all-cause death or hospitalization for heart failure (HF) after 1year (hazard ratio 4.35; 95% confidence interval, 1.27-14.83; P=0.019). The acute response of PAWP to NO differed between HF with preserved and reduced ejection fractions. Patients with Group 2 PH were tolerant of the inhaled NO test. NO-induced PAWP is a novel prognostic indicator.

Associations between Exercise-Induced Pulmonary Hemorrhage (EIPH) and Fitness Parameters Measured by Incremental Treadmill Test in Standardbred Racehorses.

Simple SummaryExercise-induced pulmonary hemorrhage (EIPH) frequently affects racehorses worldwide and has been widely associated with poor performance; however, scientific evidence supporting this observation is low. The present retrospective study aims to evaluate objectively whether the presence and grade of EIPH could affect some fitness parameters, measured during an incremental treadmill test, in poorly performing Standardbred racehorses. For this purpose, the association between EIPH and the results of a treadmill metabolic test (including blood lactate analysis and venous blood gas analysis) were evaluated in 81 Standardbred racehorses. No relationship between EIPH and aerobic/anaerobic capacity was observed, suggesting that EIPH may affect performance in a different manner. However, EIPH-affected horses were shown to reach higher hematocrit values during exercise compared to EIPH-negative horses; therefore, it may be hypothesized that hemoconcentration may take part in the pathogenesis of EIPH by increasing the pulmonary capillary pressure.Exercise-induced pulmonary hemorrhage (EIPH) is a condition affecting up to 95% of racehorses, diagnosed by detecting blood in the trachea after exercise and/or the presence of hemosiderophages in the bronchoalveolar lavage fluid (BALf). Although EIPH is commonly associated with poor performance, scientific evidence is scarce. The athletic capacity of racehorses can be quantified through some parameters obtained during an incremental treadmill test; in particular, the speed at a heart rate of 200 bpm (V200), and the speed (VLa4) and the heart rate (HRLa4) at which the blood lactate concentration reaches 4 mmol/L are considered good fitness indicators. The present retrospective study aims to evaluate whether EIPH could influence fitness parameters in poorly performing Standardbreds. For this purpose, data from 81 patients regarding their V200, VLa4, HRLa4, peak lactate, maximum speed, minimum pH, and maximum hematocrit were reviewed; EIPH scores were assigned based on tracheobronchoscopy and BALf cytology. The association between the fitness parameters and EIPH was evaluated through Spearman’s correlation analysis. No relationship between EIPH and V200, VLa4, and HRLa4 was observed. Interestingly, EIPH-positive horses showed higher hematocrit values (p = 0.0072, r = 0.47), suggesting the possible influence of the hemoconcentration on the increase of pulmonary capillary pressure as a part of the pathogenesis of EIPH.

Acetazolamide, Nifedipine and Phosphodiesterase Inhibitors: Rationale for Their Utilization as Adjunctive Countermeasures in the Treatment of Coronavirus Disease 2019 (COVID-19).

Effective treatments for Coronavirus Disease 2019 (COVID-19) outbreak are urgently needed. While anti-viral approaches and vaccines are being considered immediate countermeasures are unavailable. The aim of this article is to outline a perspective on the pathophysiology of COVID-19 in the context of the currently available clinical data published in the literature. This article appreciates clinical data published on COVID-19 in the context of another respiratory illness - high altitude pulmonary edema (HAPE). Both conditions have significant similarities that portend pathophysiologic trajectories. Following this potential treatment options emerge.Both COVID-19 and HAPE exhibit a decreased ratio of arterial oxygen partial pressure to fractional inspired oxygen with concomitant hypoxia and tachypnea. There also appears to be a tendency for low carbon dioxide levels in both as well. Radiologic findings of ground glass opacities are present in up to 86% of patients with COVID-19 in addition to patchy infiltrates. Patients with HAPE also exhibit patchy infiltrates throughout the pulmonary fields, often in an asymmetric pattern and CT findings reveal increased lung markings and ground glass-like changes as well. Widespread ground-glass opacities are most commonly a manifestation of hydrostatic pulmonary edema. Similarly, elevated fibrinogen levels in both conditions are likely an epiphenomenon of edema formation rather than coagulation activation. Autopsy results of a COVID-19 fatality revealed bilateral diffuse alveolar damage associated with pulmonary edema, pro-inflammatory concentrates, and indications of early-phase acute respiratory distress syndrome (ARDS). HAPE itself is initially caused by an increase in pulmonary capillary pressure and induces altered alveolar-capillary permeability via high pulmonary artery hydrostatic pressures that lead to a protein-rich and mildly hemorrhagic edema. It appears that COVID-19 and HAPE both discretely converge on ARDS. In light of this, a countermeasure that has been shown to be effective in the analogous condition of HAPE is Acetazolamide. Acetazolamide has a myriad of effects on different organ systems, potently reduces hypoxic pulmonary vasoconstriction, improves minute ventilation and expired vital capacity. Other therapeutics to consider that are also directed towards decreased pulmonary pressure include Nifedipine and Phosphodiesterase inhibitors.This review describes COVID-19 in parallel to HAPE. Deranged respiratory parameters that are present in both conditions are highlighted. The utilization of medications found to be effective in HAPE, for the treatment of COVID-19, is proposed. Given the medical emergency of a growing contagion and the thousands of lives at stake, expedient attempts to improve survival are needed. Acetazolamide, Nifedipine and Phosphodiesterase inhibitors may be potential countermeasures.

7 - Glypican-1 mediates endothelial hyperpermeability in a model of acute heart failure

The lungs are active participants in heart failure (HF). Increases in LVEDP augments pulmonary capillary pressure (PCP) that causes fluid filtration resulting in dyspnea and, ultimately, frank pulmonary edema (PE). The increase in PCP does not translate to the severity of dyspnea indicating that more than Starling Forces contribute to the clinical manifestation of HF. Acute increases in PCP activate glycocalyx-dependent mechanotransduction resulting in oxidative stress, eNOS activation and endothelial hyperpermeability. Herein we investigated if glypican-1 (Gpc-1) contributes to pressure-dependent hyperpermeability and PE in a model of acute HF. The isolated perfused lung preparation was used to simulate acute HF in male CD-1 (wild type, WT) and glypican-1 knockout (Gpc-1-/-) mice. Control experiments were done setting left atria pressure (PLA) at 3cm H2O for 10min; acute HF was simulated by setting PLA at 10cm H2O for 10min. Lung edema was assessed by wet-to-dry ratio (W/D); reactive oxygen species (ROS) production and eNOS activation were assessed by lucigenin chemiluminescence, DHE fluorescence and immunoblotting, respectively. WT and Gpc-1-/- mice had similar increase in PA pressure (from 8 to 10 mmHg). Deletion of Gpc-1 protected mice from pressure-induced PE (W/D [acute HF and control]), respectively in WT: 7.3±0.3 vs 4.9±0.3 and in Gpc-1-/-: 4.8±0.3 vs 4.8±0.2), prevented pressure-dependent increase in ROS production in isolated membrane fraction and in total lung homogenates (15% and 80% increase in WT). eNOS activity was increased in WT (2-fold) and decreased in Gpc-1-/- (0.5 fold) during acute HF. L-NIO inhibited edema development in WT (W/D 6.9±0.2 and 5.1±0.1 in WT and L-NIO-perfused WT, respectively). Perfusion of Gpc-1-/- lungs with NOC9 restored the response to pressure and edema development (W/D 5.1±0.1 and 5.78±0.2 in Gpc1-/- and NOC9-perfused Gpc-1-/-, respectively). Collectively, these results suggest that Gpc-1 is required for pressure-induced endothelial hyperpermeability and PE in a model of acute HF.

Glypican‐1 Mediates Endothelial Hyper‐permeability in a Model of Acute Heart Failure

Accumulating evidence indicates that the lungs are active participants in the pathogenesis of heart failure (HF). Increases in left ventricular end diastolic pressure (LVEDP) leads to elevated pulmonary capillary pressure (PCP) that causes fluid filtration resulting in dyspnea and, ultimately, frank pulmonary edema (PE). However, the severity of dyspnea does not directly relate to the increase in PCP indicating that the clinical manifestation of HF cannot be solely explained by changes in Starling forces. Acute increases in PCP activate glycocalyx‐dependent signaling (endothelial mechanotransduction) that result in oxidative stress, eNOS activation and endothelial hyper‐permeability. Herein we sought to investigate if glypican‐1, a component of the glycocalyx, contributes to pressure‐dependent hyper‐permeability and PE in a model of acute HF. The isolated perfused lung preparation was used to simulate acute HF in male CD‐1 (wild type, WT) and glypican‐1 knockout (Gpc‐1 KO) mice (6 weeks old). Briefly, mice were anesthetized with isoflurane, tracheostomized and mechanically ventilated. Pulmonary artery and left atria were cannulated and in‐line pressure transducers recorded arterial and left atrial pressure; lungs were perfused at 2 mL/min with a Krebs‐Ringer 3% BSA buffer. Control experiments were done setting left atria pressure (PLA) at 3 cm H2O for 10 minutes; acute heart failure was simulated by setting PLA at 10 cm H2O for 10 minutes. Lung edema was assessed by lung wet‐to‐dry ratio; reactive oxygen species (ROS) production and eNOS activation were assessed as indices of mechanotransduction activation by lucigenin enhanced chemiluminescence and immunoblotting, respectively. NADPH oxidase activity was measured by dihydroethidium fluorescence in isolated membrane‐fracions. WT and Gpc‐1 KO mice had similar increase in pulmonary artery pressure (from 8 to 10 mmHg). Deletion of glypican‐1 protected mice from pressure‐induced PE (wet‐to dry ratio [high and low pressure, respectfully] in WT: 7.3±0.3 vs 4.9±0.3 and in Gpc‐1 KO: 4.8±0.3 vs 4.8±0.2), prevented pressure‐dependen increase in NADPH oxidase activity (15% increase in WT) and in ROS production (80% increase in WT). Moreover, while WT mice showed increased eNOS activation (2‐fold) during acute HF, Gpc‐1 KO mice showed reduced eNOS activation (0.5 fold) indicating that Gpc‐1 is a determinant for mechanotransduction signaling. Taken together, these results suggest that Gpc‐1 activation by pressure leads to endothelial hyper‐permeability due to ROS and NO‐dependent pathways and contributes to PE in an in situ model of acute HF.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Mechanical versus humoral determinants of brain death-induced lung injury.

BackgroundThe mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations.MethodsBrain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury.ResultsIntracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score.ConclusionsBrain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone.

Pulmonary vascular distensibility predicts aerobic capacity in healthy individuals

It has been suggested that shallow slopes of mean pulmonary artery pressure (MPPA)–cardiac output (Q) relationships and pulmonary transit of agitated contrast during exercise may be associated with a higher maximal aerobic capacity V(O(2)max). If so, individuals with a higher V(O(2)max) could also exhibit a higher pulmonary vascular distensibility and increased pulmonary capillary blood volume during exercise. Exercise stress echocardiography was performed with repetitive injections of agitated contrast and measurements of MPPA, Q and lung diffusing capacities for carbon monoxide (D(L,CO)) and nitric oxide (D(L,CO)) in 24 healthy individuals. A pulmonary vascular distensibility coefficient α was mathematically determined from the slight natural curvilinearity of multipoint MPPA–Q plots. Membrane (D(m)) and capillary blood volume (V(c)) components of lung diffusing capacity were calculated. Maximal exercise increased MPPA, cardiac index (CI), D(L,CO) and (D(L,NO). The slope of the linear best fit of MPPA–CI was 3.2 ± 0.5 mmHg min l(-1) m(2) and α was 1.1 ± 0.3% mmHg(-1). A multivariable analysis showed that higher α and greater V(c) independently predicted V(O(2)max). All individuals had markedly positive pulmonary transit of agitated contrast at maximal exercise, with increases proportional to increases in pulmonary capillary pressure and V(c). Pulmonary transit of agitated contrast was not related to pulse oximetry arterial oxygen saturation. Therefore, a more distensible pulmonary circulation and a greater pulmonary capillary blood volume are associated with a higher V(O(2)max) in healthy individuals. Agitated contrast commonly transits through the pulmonary circulation at exercise, in proportion to increased pulmonary capillary pressures.

Assessment of vascular permeability in an ovine model of acute lung injury and pneumonia-induced Pseudomonas aeruginosa sepsis

To assess the time changes and mechanism of pulmonary and peripheral vascular permeability in sheep with acute lung injury and sepsis. Prospective, controlled, randomized trial. University research laboratory. A total of 21 chronically instrumented, adult female sheep. Sheep were instrumented with lung and prefemoral lymph fistulas and allocated to either an uninjured control group (n = 5) or sepsis group (n = 5). The sheep in the sepsis group received cotton smoke inhalation injury followed by instillation of Pseudomonas aeruginosa into the lungs. All sheep were mechanically ventilated and fluid resuscitated for the entire duration of the 24-hr experiment. Additional sheep (n = 11) received injury and were killed at different time points for the measurement of vascular endothelial growth factor in lung tissue. The injury induced a hypotensive-hyperdynamic circulation; increases in pulmonary capillary pressure, net fluid balance, lung and prefemoral lymph flow and protein content, lung water content, abdominal and thoracic fluid and protein content, neutrophil accumulation in the lung, and vascular endothelial growth factor expression in lung tissue; and decreases in PaO2/FiO2 ratio, plasma protein concentration, plasma oncotic pressure, and myocardial contractility. Lung edema formation in this model was the result of marked increases in both pulmonary microvascular permeability and pressure. Pulmonary vascular hyperpermeability peaked 12 hrs postinjury and was related to vascular endothelial growth factor overexpression. Early myocardial failure was a potential contributor to the constant increase in pulmonary capillary pressure. The sepsis-induced increase in peripheral microvascular permeability was associated with significant accumulation of fluid and protein in the third space.

Mitralinsuffizienz

Mitral regurgitation is the second most frequent reason for valve surgery. The most important causes of mitral regurgitation are degenerative valve disease (mitral valve prolapse), left ventricular impairment and dilatation (in coronary artery disease or dilated cardiomyopathy), and infective endocarditis. The regurgitation of blood from the left ventricle into the left atrium leads to dilatation of the left atrium, increase in pulmonary capillary pressure and pulmonary congestion. In chronic severe mitral regurgitation, the left ventricle dilates and becomes impaired over time. Key symptoms are fatigue and dyspnea on exertion. The most prominent physical sign is the characteristic systolic murmur. Echocardiography identifies severity, delineates morphology, and estimates the impact of mitral regurgitation on left ventricular function. Importantly, echocardiography identifies candidates for mitral valve repair. Symptomatic patients and asymptomatic patients with impaired left ventricular function should be operated. If possible, valve repair is preferred over valve replacement to better preserve left ventricular function and to avoid the need for postoperative anticoagulation (except if atrial fibrillation persists).

Nitrovasodilator repletion increases TNF-alpha-induced pulmonary edema.

We tested the hypothesis that nitrovasodilator repletion enhances tumor necrosis factor-alpha (TNF-alpha) -induced pulmonary edema. Lungs were isolated from control guinea pigs or 4 h after the intraperitoneal injection of TNF-alpha (1.60 x 10(5) U/kg). In the control and TNF-alpha-injected lungs, the thromboxane mimetic U-46619 (155 pmol/min) caused increases in pulmonary capillary pressure (Ppc) and lung weight (delta W). In control lungs, the nitrovasodilator agonist S-nitroso-N-acetyl-penicillamine (SNAP, 1 microM) attenuated the U-46619-induced increases in Ppc. In lungs injected with TNF-alpha, SNAP had no effect on Ppc and increased delta W. The peroxynitrite (ONOO-) scavenger urate (35 mM) prevented the TNF-alpha +SNAP-induced increases in Ppc and delta W. In addition, chemically synthesized ONOO- (4.0 mM) enhanced U-46619-induced increases in delta W. The data indicate that nitric oxide repletion enhances TNF-alpha-induced pulmonary edema, possibly via ONOO-.

Effects of thromboxane A2 analogue on vascular resistance distribution and permeability in isolated blood-perfused dog lungs

This study was designed to determine the effects of thromboxane A2 (TxA2) on the distribution of vascular resistance, lung weight, and microvascular permeability in isolated dog lungs perfused at a constant pressure with autologous blood. The stable TxA2 analogue (STA2; 30 micrograms, n = 5) caused an increase in pulmonary capillary pressure (Pc) assessed as double-occlusion pressure to 14.0 +/- 0.4 mmHg from the baseline of 7.9 +/- 0.3 mmHg with progressive lung weight gain. Pulmonary vascular resistance increased threefold exclusively due to pulmonary venoconstriction. Pulmonary venoconstriction was confirmed in lungs perfused in a reverse direction from the pulmonary vein to the artery (n = 5), as evidenced by marked precapillary vasoconstriction and a sustained lung weight loss. Furthermore, in lungs perfused at a constant blood flow (n = 5), STA2 also caused selective pulmonary venoconstriction. Vascular permeability measured by the capillary filtration coefficient and the isogravimetric Pc at 30 and 60 min after STA2 infusion did not change significantly from baseline in any lungs studied. Moreover, elevation of Pc by raising the venous reservoir of the intact lobes (n = 5) to the same level as the STA2 lungs caused a greater or similar weight gain compared with the STA2 lungs. Thus, we conclude that TxA2 constricts selectively the pulmonary vein resulting in an increase in Pc and lung weight gain without significant changes in vascular permeability in isolated blood-perfused dog lungs.

Hemodynamic Effects of α–Adrenergic Blockade With Prazosin in Cirrhotic Patients With Portal Hypertension

This study was aimed at investigating whether the blockade of alpha 1-adrenergic receptors could reduce portal pressure in cirrhosis. Splanchnic and systemic hemodynamics were measured in 12 cirrhotic patients with esophageal varices at baseline and 1 hr after oral administration of 2 mg of prazosin (acute study). Measurements were repeated in 10 of these 12 patients after a 3-mo course of 5 mg/12 hr of prazosin (long-term study). Short-term prazosin significantly lowered the hepatic venous pressure gradient from 20.1 +/- 1.3 to 14.4 +/- 0.9 mm Hg (-25.7%) (p < 0.01), and chronic prazosin reduced it to 16.5 +/- 1.3 mm Hg (-19.1%) (p < 0.01). Hepatic blood flow was increased, thus changes in the hepatic venous pressure gradient resulted from a reduction in the estimated hepatic vascular resistance. Reductions in hepatic venous pressure gradient achieved after short-term and long-term prazosin were not significantly different. Reductions in mean arterial pressure and systemic vascular resistance were significantly greater after short-term than after long-term prazosin. Long-term prazosin was associated with significant increases in hepatic and intrinsic hepatic clearances of indocyanine green. This therapy also led to an increase in pulmonary capillary pressure (+ 28.6%, p < 0.05) and body weight (+ 3.06%, p < 0.01) and a decrease in hematocrit (-6.1%, p < 0.05) and urinary sodium excretion (-22.6%, p < 0.05). In contrast, there were no hemodynamic changes in a group of six cirrhotic patients receiving placebo. In cirrhotic patients, short-term prazosin lowers portal pressure by decreasing hepatic vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Furosemide attenuates the exercise-induced increase in pulmonary artery wedge pressure in horses

Summary Right atrial (ra), right ventricular (rv), pulmonary artery (pa), and pulmonary artery wedge (paw) pressures were examined, using catheter-mounted micromanometers, in 8 healthy horses at rest and during galloping on a treadmill at belt speeds of 8, 10, and 13 m/s. The in vivo signals from the micromanometers were matched with those from conventional fluid-filled catheter transducers leveled at the scapulohumeral joint. Thirty minutes after completing control exercise measurements, furosemide was administered iv at a dosage of 1 mg/kg of body weight, and resting, as well as exercise, measurements were repeated 4 hours later. Studies also were performed on a separate day, when only postfurosemide resting and exercise data were collected. Prefurosemide and postfurosemide heart rate values for rest (37 ± 2 beats/min, mean ± sem), as well as for exercise (213 ± 5 beats/min at 13 m/s), were similar. Prefurosemide mean ra, pa, and paw pressures were increased significantly (P &lt; 0.05) from resting values of 8 ± 2, 31 ± 2, and 18 ± 2 mm of Hg, respectively, to 44 ± 4,89 ± 5, and 56 ± 4mm of Hg with exercise at 13 m/s. Furosemide administration resulted in marked diuresis, and resting mean ra, pa, and paw pressures decreased significantly (P &lt; 0.05) to 1 ± 1, 27 ± 2, and 11 ± 2 mm of Hg, respectively, 4 hours after furosemide administration. Although pressures increased markedly with exercise (corresponding values being 31 ± 5, 79 ± 6, and 44 ± 4 mm of Hg), these 4-hour postfurosemide exercise values were significantly (P &lt; 0.05) less than those recorded with prefurosemide exertion. Intravascular pulmonary capillary pressure, calculated as the average of mean pa and paw pressures, during prefurosemide exercise (73 ± 5 mm of Hg) significantly (P &lt; 0.05) exceeded that during exercise performed 4 hours after furosemide administration (61 ± 5mm of Hg). Attenuation by furosemide of the exercise-induced increase in pulmonary capillary pressure may have a role in limiting or reducing the extent of exercise-induced pulmonary hemorrhage in horses.

Pulmonary venodilation by isoflurane improves gas exchange during Escherichia coli bacteremia.

To determine how isoflurance affects the longitudinal distribution of pulmonary vascular resistance and pulmonary gas exchange during Escherichia coli bacteremia. Prospective, controlled study with open-label assignment of animals to two groups. Laboratory. Goehingen minipigs. Induction of acute respiratory failure by a 4-hr infusion of live E. coli bacteria in 12 animals; six animals anesthetized with methohexital/piritramide; six animals anesthetized with isoflurane. The control group consisted of four animals that received the same surgical procedure, but no E. coli infusion. Two animals were anesthetized with methohexital/piritramide and two with isoflurane, respectively. Cardiac output and pressures were measured by means of an arterial catheter, Swan-Ganz catheter, and a left atrial catheter. Effective pulmonary capillary pressure was evaluated graphically from a pulmonary artery occlusion pressure decay. Arterial-alveolar PO2 ratio was calculated to evaluate pulmonary function. Measurements were performed before and after 1, 2, and 3.5 hrs of E. coli infusion. Statistical significance was tested with analysis of variance (ANOVA). E. coli infusion caused hypodynamic shock, an increase in pre- and postcapillary pulmonary vascular resistance and respiratory failure. Postcapillary pressure gradient and effective pulmonary capillary pressure were lower in the isoflurane-group. Methohexital-anesthetized animals developed pulmonary dysfunction after 1 hr of bacteremia, whereas isoflurane-anesthetized animals developed pulmonary dysfunction after 3.5 hrs of E. coli infusion (significantly different, ANOVA, p < .05). There were no significant changes in the sham group. Isoflurane is a pulmonary venodilator. During lethal E. coli infusion, it ameliorates the increase in pulmonary capillary pressure and preserves pulmonary function until vascular permeability increases.

Observations on plasma ANP levels during short-term transient myocardial ischemia produced by PTCA in patients with LAD stenosis.

Ten patients with coronary artery disease and stable angina (mean age fifty-seven) were included in the study. Five of the patients had normal left ventricular function, 5 had local hypokinesia or akinesia; 8 had one-stem and 2 had two-stem disease, but all had left anterior descending (LAD) lesions ranging from 75% to 100%. Ejection fraction varied between 35% and 75% (mean 59%). Immunoreactive atrial natriuretic polypeptide (ANP) levels in the femoral vein (FV) and the coronary sinus (CS) were measured before, immediately after, and up to twenty-four hours after percutaneous transluminal coronary angioplasty (PTCA) of the LAD. ANP secretion increased by 83% (FV) and 11% (CS) within minutes after PTCA and reached control levels after thirty to sixty minutes. In patients with hypokinesia of the anterior wall, ANP secretion was significantly lower, 48% (FV) and 11% (CS) respectively. ANP secretion during PTCA was higher in patients with concomitant increase in pulmonary capillary pressure (PCP) but was also observed without an increase of PCP, suggesting ventricular ANP secretion. IN conclusion, transient myocardial ischemia leads to immediate ANP secretion even in the absence of significant pressure elevation in the left atrium. As a part of the continuous medical education program of the American College of Angiology the second part of the paper reviews the mechanisms that allow the ischemic heart to counteract the ischemic condition and thus to escape from myocardial infarction. A review of this subject is presently not available in the literature.

Pulmonary Capillary Pressure Measurement During Global Hypoxia in Sheep

Analysis of the pressure decay following pulmonary artery occlusion can be used to determine pulmonary capillary pressure and to calculate the magnitudes of the arterial and venous components of pulmonary vascular resistance. The separation of pulmonary vascular resistance into components has been termed "the longitudinal distribution of pulmonary vascular resistance" to emphasize the fact that different pressures occur at a number of sites in the pulmonary circulation. The longitudinal distribution of pulmonary vascular resistance is closely related to pulmonary capillary pressure. Several methods of data analysis have been proposed to determine pulmonary capillary pressure from the pressure decay following pulmonary artery occlusion. In this study, three methods of data analysis were applied to the model of hypoxic pulmonary vasoconstriction to evaluate the validity of the methodology in a well known model. Pulmonary artery occlusion pressure decay curves were obtained from eight halothane-anesthetized sheep during control conditions (FIO2 = 0.99) and during hypoxic ventilation (FIO2 = 0.14). Analysis of the pulmonary artery occlusion pressure decay curves indicated the following results: 1) Hypoxia increased mean pulmonary artery pressure by 105% and increased pulmonary vascular resistance by 149%; 2) the increase in the calculated arterial component of pulmonary vascular resistance accounted for 88% of the increase in pulmonary vascular resistance with hypoxia; and 3) hypoxia produced only a 1.0 mm Hg increase in pulmonary capillary pressure. These results are consistent with other evidence showing that hypoxia primarily produces precapillary pulmonary vasoconstriction and has little effect on pulmonary capillary pressure. Pulmonary artery occlusion pressure decay curve analysis appears to be a valid technique for the measurement of pulmonary capillary pressure during hypoxia in intact anesthetized animals.

Permeability Pulmonary Edema following Lung Resection

The etiology of edema associated with pulmonary resection was investigated in five patients during the immediate postoperative period. Three patients received pneumonectomy while two patients had one lobe resected. All patients suffered from severe respiratory distress and had x-ray evidence of diffuse interstitial pulmonary edema within 12 hours of surgery. Hemodynamic data were obtained with radial and pulmonary artery catheters. Edema fluid was obtained along with blood samples for simultaneous determination of protein and albumin content. All patients studied had normal or high cardiac output, normal cardiac filling pressures, and edema fluid protein to serum protein ratio of 0.6 or greater suggestive of permeability changes contributing to edema fluid accumulation. Calculated shunt fraction exceeded 25 percent in all patients. Pulmonary edema has been noted in patients following pulmonary resection in the early postoperative period. In patients reviewed here, two factors appeared to be significant. First is an increase in pulmonary capillary pressure associated with passage of a normal to high cardiac output in a reduced volume pulmonary vascular bed. The second factor, as demonstrated by protein content in the edema fluid, is injury to the alveolar capillary membrane.

Pulmonary vascular response to leukotriene D4 in unanesthetized sheep: role of thromboxane.

We examined the pulmonary vascular response to an intravenous leukotriene D4 (LTD4) injection of (1 microgram X kg-1 X min-1 for 2 min) immediately followed by infusion of 0.133 microgram X kg-1 X min-1 for 15 min in awake sheep prepared with lung lymph fistulas. LTD4 resulted in rapid generation of thromboxane A2 as measured by an increase in plasma thromboxane B2 concentration. The thromboxane B2 generation was associated with increases in pulmonary arterial and pulmonary arterial wedge pressures while left atrial pressure did not change significantly. Pulmonary lymph flow (Qlym) increased (P less than 0.05) transiently from base line 6.87 +/- 1.88 (SE) ml/h to maximum value of 9.77 +/- 1.27 at 15 min following the LTD4 infusion. The maximum increase in Qlym was associated with an increase in the estimated pulmonary capillary pressure. The increase in Qlym was not associated with a change in the lymph-to-plasma protein concentration (L/P) ratio. Thromboxane synthetase inhibition with dazoxiben (an imidazole derivative) prevented thromboxane B2 generation after LTD4 and also prevented the increases in pulmonary vascular pressures and Qlym. We conclude that LTD4 in awake sheep increases resistance of large pulmonary veins. The small transient increase in Qlym can be explained by the increase in pulmonary capillary pressure. Thromboxane appears to mediate both the pulmonary hemodynamic and lymph responses to LTD4 in sheep.

The pulmonary interstitium in capillary exchange.

When capillaries filter excessive fluid, tissue fluid pressure increases, tissue colloid osmotic pressure decreases, and lymph flow increases. The change in tissue forces and flows have been termed edema safety factors since they act to oppose alterations in pulmonary capillary pressure. It is well known that pulmonary capillary pressure can be acutely increased by approximately 20 mm Hg before fluid enters the alveoli, and that the changes in the tissue forces are responsible for this phenomenon. The decrease in interstitial colloid osmotic pressure appears to account for approximately 50% of the tissue's ability to oppose increases in pulmonary capillary pressure. The tissue colloids change because the capillaries filter a protein-poor fluid, and the exclusion of plasma proteins decreases with increasing interstitial volume. Tissue pressure, at least in the perivascular regions, increases with tissue hydration and provides another major tissue force opposing capillary filtration. The contribution of lymph flow to the overall edema safety factor is difficult to estimate at the present time. However, it is possible that the pressure drop associated with the flow of interstitial fluid between the alveolar septal interstitium and the larger perivascular spaces could serve as an edema safety factor, rather than the standard lymphatic flow pressure drop across the capillary membrane. To calculate the standard lymph flow contribution to the total edema safety factor, total lymph flow [LF] and the filtration coefficient of the capillaries [Kf,c] must be known, i.e., Capillary Wall Drop = LF/Kf,c. For normal lung lymph flows and Kf,c's, it would appear that this factor is small. However, if the total pressure drop for fluid movement through the entire lung tissue is used to estimate the lymphatic factor, then it may represent a major portion of the edema safety factor, i.e., Total Pressure Drop = LF/[Kf,cKf,t]/Kf,c + Kf,t] where Kf,t is the filtration coefficient of the tissues. Tissue forces at different site within the lung tissue are presently under intense investigation in serveral laboratories. The next years should provide the necessary information to discuss fluid accumulation in lung tissue in terms of local transcapillary forces rather than the average forces that are now the "present state of the art."