Site of pulmonary vasodilation by inhaled nitric oxide in the perfused lung

1995 ◽  
Vol 78 (5) ◽  
pp. 1745-1749 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis
Keyword(s):  
Nitric Oxide ◽  
Vascular Occlusion ◽  
Inhaled Nitric Oxide ◽  
Krebs Solution ◽  
Total Resistance ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Perfused Lung ◽  
Occlusion Technique ◽  
Inhaled No

To determine the site of inhaled nitric oxide (NO)-induced pulmonary vasodilation, a double vascular occlusion technique was used with rabbit lungs ventilated and perfused at 20 ml/min with Krebs solution containing 3% dextran and 30 microM indomethacin. Inhaled NO (120 ppm for 3 min) reduced pulmonary vasoconstriction produced by U-46619 infusion (0.5–1.2 nmol/min), significantly decreasing total resistance (RT) [1,080 +/- 51 (SE) vs. 1,545 +/- 109 mmHg.l–1.min; P < 0.01]. Acetylcholine infusion (ACh; 2–5 nmol/min) and nitroglycerin (NTG; 0.35 mumol) likewise decreased RT. Arterial resistance (Ra) was also significantly less with inhaled NO, ACh, and NTG compared with U-46619 alone. Venous resistance (Rv), however, was unchanged. When the direction of perfusion was reversed in the lung, inhaled NO, ACh, and NTG significantly decreased RT compared with U-46619 alone, and Rv was also reduced by all three agents. After electrolysis-induced acute lung injury, inhaled NO significantly reduced both RT and Ra compared with U-46619 alone, whereas Rv was unaffected. Our results demonstrate that inhaled NO gas affects primarily the arterial (precapillary) component of the pulmonary circulation but, under conditions of extreme venous constriction, may dilate the postcapillary component as well.

Pulmonary vasodilation by inhaled nitric oxide after endothelial injury

1992 ◽  
Vol 73 (5) ◽  
pp. 2179-2183 ◽  
Author(s):  
S. Rimar ◽  
C. N. Gillis
Keyword(s):  
Nitric Oxide ◽  
Methylene Blue ◽  
Free Radical ◽  
Perfusion Pressure ◽  
Inhaled Nitric Oxide ◽  
Arterial Perfusion ◽  
Pulmonary Vasodilation ◽  
Pulmonary Vasoconstriction ◽  
Pulmonary Arterial ◽  
Inhaled No

Inhaled nitric oxide gas (NO) has recently been shown to reverse experimentally induced pulmonary vasoconstriction. To examine the effect of free radical injury and methylene blue exposure on inhaled NO-induced pulmonary vasodilation we studied ventilated rabbit lungs perfused with Krebs solution containing 3% dextran and indomethacin. When NO gas (120 ppm) was added to the inhaled mixture for 3 min, the elevated pulmonary arterial perfusion pressure (Ppa) induced by the thromboxane analogue U-46619 was significantly reduced [8 +/- 2 (SE) mmHg]. Acetylcholine similarly reduced Ppa (9 +/- 1 mmHg). After free radical injury and methylene blue exposure, inhaled NO again produced significant vasodilation (5 +/- 1 and 9 +/- 2 mmHg, respectively), but acetylcholine resulted in an increase in Ppa (-9 +/- 3 and -4 +/- 1 mmHg, respectively). These data demonstrate that pulmonary vasodilation produced by inhaled NO is unaffected by free radical injury or methylene blue in the intact lung despite concomitant reversal of acetylcholine-induced vasodilation.

Sites of inhaled NO-induced vasodilation during hypoxia and U-46619 infusion in isolated lamb lungs

1995 ◽  
Vol 268 (4) ◽  
pp. H1422-H1427 ◽  
Author(s):  
M. L. Tod ◽  
D. C. O'Donnel ◽  
J. B. Gordon
Keyword(s):  
Pressure Gradient ◽  
Pulmonary Veins ◽  
Vascular Occlusion ◽  
Similar Degree ◽  
Pressure Gradients ◽  
Small Arteries ◽  
Pulmonary Vasoconstriction ◽  
Occlusion Technique ◽  
Inhaled No ◽  
Rapid Binding

The sites of relaxation in response to inhaled nitric oxide (NO) were investigated using the vascular occlusion technique in isolated blood-perfused lungs from 1- to 3-mo-old lambs. In one group of 10 lungs, inhaled NO (45 ppm) was administered during hypoxia- and U-46619-induced pulmonary vasoconstriction. In a second group of 5 lungs, responses to inhaled NO and infused sodium nitroprusside (SNP, 3 micrograms.kg-1.min-1) during U-46619-induced hypertension were compared. Hypoxia caused significant pulmonary vasoconstriction, with increases in the pressure gradients of large and small arteries and small veins, as defined by vascular occlusion. Inhaled NO significantly reduced the total pulmonary pressure gradient by 67% and relaxed both large and small arteries. Infusion of U-46619 caused significant increases in all segmental pressure gradients. While inhaled NO was effective in relaxing the large and small arteries and the small veins, it had no effect on the large veins. Infusions of SNP, a nitrosovasodilator thought to act like endogenous NO, caused a similar degree of total relaxation as NO (81 vs. 77%, respectively). However, in contrast to inhaled NO, SNP was effective in reducing the pressure gradient of the large pulmonary veins. These results suggest that rapid binding to and thus inactivation of inhaled NO by hemoglobin limit its efficacy as a pulmonary venous dilator.

Radical Scavengers Protect Murine Lungs from Endotoxin-induced Hyporesponsiveness to Inhaled Nitric Oxide

2002 ◽  
Vol 96 (4) ◽  
pp. 926-933 ◽  
Author(s):  
Yehuda Raveh ◽  
Fumito Ichinose ◽  
Pini Orbach ◽  
Kenneth D. Bloch ◽  
Warren M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Reactive Oxygen Species ◽  
Polyethylene Glycol ◽  
Reactive Oxygen ◽  
Inhaled Nitric Oxide ◽  
Oxygen Species ◽  
Pulmonary Vasodilation ◽  
Vasodilator Response ◽  
Pulmonary Vasodilator ◽  
Inhaled No

Background Sepsis is associated with an impaired pulmonary vasodilator response to inhaled nitric oxide (NO). A combination of NO and other inflammatory mediators appears to be responsible for endotoxin-induced pulmonary vascular hyporesponsiveness to inhaled NO. The authors investigated whether scavengers of reactive oxygen species could preserve inhaled NO responsiveness in endotoxin-challenged mice. Methods The vasorelaxation to inhaled NO was studied in isolated, perfused, and ventilated lungs obtained from mice 16 h after an intraperitoneal challenge with saline or 50 mg/kg Escherichia coli lipopolysaccharide. In some mice, challenge with saline or lipopolysaccharide was followed by intraperitoneal administration of N-acetylcysteine, dimethylthiourea, EUK-8, or polyethylene glycol-conjugated catalase. Results The pulmonary vasodilator response of U46619-preconstricted isolated lungs to ventilation with 0.4, 4, and 40 ppm inhaled NO in lipopolysaccharide-challenged mice was reduced to 32, 43, and 60%, respectively, of that observed in saline-challenged mice (P &lt; 0.0001). Responsiveness to inhaled NO was partially preserved in lipopolysaccharide-challenged mice treated with a single dose of N-acetylcysteine (150 or 500 mg/kg) or 20 U/g polyethylene glycol-conjugated catalase (all P &lt; 0.05 vs. lipopolysaccharide alone). Responsiveness to inhaled NO was fully preserved by treatment with either dimethylthiourea, EUK-8, two doses of N-acetylcysteine (150 mg/kg administered 3.5 h apart), or 100 U/g polyethylene glycol-conjugated catalase (all P &lt; 0.01 vs. lipopolysaccharide alone). Conclusions When administered to mice concurrently with lipopolysaccharide challenge, reactive oxygen species scavengers prevent impairment of pulmonary vasodilation to inhaled NO. Therapy with scavengers of reactive oxygen species may provide a means to preserve pulmonary vasodilation to inhaled NO in sepsis-associated acute lung injury.

Inhaled nitric oxide: dose response and the effects of blood in the isolated rat lung

1993 ◽  
Vol 75 (3) ◽  
pp. 1278-1284 ◽  
Author(s):  
G. F. Rich ◽  
C. M. Roos ◽  
S. M. Anderson ◽  
D. C. Urich ◽  
M. O. Daugherty ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Angiotensin Ii ◽  
Dose Response ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasodilation ◽  
Pulmonary Arterial ◽  
Relationship Of ◽  
Inhaled No ◽  
Isolated Rat

Inhaled nitric oxide (NO) is a vasodilator selective to the pulmonary circulation. Using isolated rat lungs, we determined the dose-response relationship of NO and the role of blood in mediating pulmonary vasodilation and selectivity. Inhaled 20, 50, 100, and 1,000 ppm NO attenuated (P < 0.001) hypoxic pulmonary vasoconstriction by 16.1 +/- 4.9, 22.6 +/- 6.8, 28.4 +/- 3.5, and 69.3 +/- 4.2%, respectively. Inhaled 13, 34, 67, and 670 ppm NO attenuated the increase in pulmonary arterial pressure secondary to angiotensin II more (P < 0.001) in Greenberg-Bohr buffer- (GB) than in blood-perfused lungs (51.7 +/- 9.9, 71.9 +/- 8.9, 78.2 +/- 5.3, and 91.9 +/- 2.1% vs. 14.3 +/- 4.1, 23.8 +/- 4.6, 28.4 +/- 3.8, and 55.5 +/- 5.9%, respectively). Samples from GB- but not blood-perfused lungs contained NO (93.0 +/- 26.3 nM). Intravascular NO attenuated the response to angiotensin II more (P < 0.001) in GB- (with and without plasma) than in blood- (hematocrit = 41 and 5%) perfused lungs (75.6 +/- 6.4 and 70.9 +/- 4.8% vs. 22.2 +/- 2.4 and 39.4 +/- 7.6%). In conclusion, inhaled NO produces reversible dose-dependent pulmonary vasodilation over a large range of concentrations. Inhaled NO enters the circulation, but red blood cells prevent systemic vasodilation and also a significant amount of pulmonary vasodilation.

Inhaled nitric oxide does not alter the longitudinal distribution of pulmonary vascular resistance

1995 ◽  
Vol 78 (1) ◽  
pp. 341-348 ◽  
Author(s):  
D. M. Lindeborg ◽  
B. P. Kavanagh ◽  
K. Van Meurs ◽  
R. G. Pearl
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Dose Range ◽  
Venous Occlusion ◽  
Inhaled Nitric Oxide ◽  
Longitudinal Distribution ◽  
Perfused Lung ◽  
Inhaled No

Because the effects of inhaled nitric oxide (NO) may be localized to its site of delivery, we studied the effects of inhaled NO on the longitudinal distribution of pulmonary vascular resistance during pulmonary hypertension in perfused rabbit lungs. Before NO administration, pulmonary hypertension was produced by infusion of the thromboxane A2 mimetic U-46619 in all lungs. Pulmonary vascular resistance was divided into arterial, microvascular, and venous components by arterial and venous occlusion techniques. In the buffer-perfused lung, all doses of inhaled NO (5, 20, and 80 ppm) produced small decreases (approximately 3 mmHg) in pulmonary arterial pressure (Ppa), with equivalent proportional reductions in all segmental vascular resistances. Similar results were obtained after an extended inhaled NO dose range of 20, 80, and 240 ppm. In the buffer-perfused lung, inhibition of endogenous NO synthesis with NG-nitro-L-arginine methyl ester (L-NAME) potentiated the effects of U-46619. Subsequent inhaled NO administration produced larger decreases (approximately 7 mmHg) in Ppa with equivalent proportional reductions in all segmental vascular resistances. In the blood-perfused lung, L-NAME did not alter baseline pulmonary pressures. Administration of inhaled NO during U-46619-induced pulmonary hypertension produced dose-related decreases in Ppa. The highest dose (80 ppm) of inhaled NO decreased Ppa by 3.5 mmHg, with equivalent proportional reductions in all segmental vascular resistances.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhaled Nitric Oxide at Birth Reduces Pulmonary Vascular Resistance and Improves Oxygenation in Preterm Lambs

Children ◽  
2021 ◽  
Vol 8 (5) ◽  
pp. 378
Author(s):  
Satyan Lakshminrusimha ◽  
Sylvia F. Gugino ◽  
Krishnamurthy Sekar ◽  
Stephen Wedgwood ◽  
Carmon Koenigsknecht ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Preterm Infants ◽  
Vascular Resistance ◽  
Inhaled Nitric Oxide ◽  
Persistent Pulmonary Hypertension ◽  
Inhaled No ◽  
Birth Preterm

Resuscitation with 21% O2 may not achieve target oxygenation in preterm infants and in neonates with persistent pulmonary hypertension of the newborn (PPHN). Inhaled nitric oxide (iNO) at birth can reduce pulmonary vascular resistance (PVR) and improve PaO2. We studied the effect of iNO on oxygenation and changes in PVR in preterm lambs with and without PPHN during resuscitation and stabilization at birth. Preterm lambs with and without PPHN (induced by antenatal ductal ligation) were delivered at 134 d gestation (term is 147–150 d). Lambs without PPHN were ventilated with 21% O2, titrated O2 to maintain target oxygenation or 21% O2 + iNO (20 ppm) at birth for 30 min. Preterm lambs with PPHN were ventilated with 50% O2, titrated O2 or 50% O2 + iNO. Resuscitation with 21% O2 in preterm lambs and 50%O2 in PPHN lambs did not achieve target oxygenation. Inhaled NO significantly decreased PVR in all lambs and increased PaO2 in preterm lambs ventilated with 21% O2 similar to that achieved by titrated O2 (41 ± 9% at 30 min). Inhaled NO increased PaO2 to 45 ± 13, 45 ± 20 and 76 ± 11 mmHg with 50% O2, titrated O2 up to 100% and 50% O2 + iNO, respectively, in PPHN lambs. We concluded that iNO at birth reduces PVR and FiO2 required to achieve target PaO2.

Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension

1998 ◽  
Vol 84 (2) ◽  
pp. 435-441 ◽  
Author(s):  
Christophe Adrie ◽  
Fumito Ichinose ◽  
Alexandra Holzmann ◽  
Larry Keefer ◽  
William E. Hurford ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Vascular Resistance ◽  
Pulmonary Circulation ◽  
Half Life ◽  
Hemodynamic Effects ◽  
Pulmonary Vasodilation ◽  
Short Half Life ◽  
Acute Pulmonary Hypertension ◽  
Inhaled No

Adrie, Christophe, Fumito Ichinose, Alexandra Holzmann, Larry Keefer, William E. Hurford, and Warren M. Zapol. Pulmonary vasodilation by nitric oxide gas and prodrug aerosols in acute pulmonary hypertension. J. Appl. Physiol. 84(2): 435–441, 1998.—Sodium 1-( N, N-diethylamino)diazen-1-ium-1,2-diolate {DEA/NO; Et2N[N(O)NO]Na} is a compound that spontaneously generates nitric oxide (NO). Because of its short half-life (2.1 min), we hypothesized that inhaling DEA/NO aerosol would selectively dilate the pulmonary circulation without decreasing systemic arterial pressure. We compared the pulmonary selectivity of this new NO donor with two other reference drugs: inhaled NO and inhaled sodium nitroprusside (SNP). In seven awake sheep with pulmonary hypertension induced by the infusion of U-46619, we compared the hemodynamic effects of DEA/NO with those of incremental doses of inhaled NO gas. In seven additional awake sheep, we examined the hemodynamic effects of incremental doses of inhaled nitroprusside (i.e., SNP). Inhaled NO gas selectively dilated the pulmonary vasculature. Inhaled DEA/NO produced nonselective vasodilation; both systemic vascular resistance (SVR) and pulmonary vascular resistance (PVR) were reduced. Inhaled SNP selectively dilated the pulmonary circulation at low concentrations (≤10−2 M), inducing a decrease of PVR of up to 42% without any significant decrease of SVR (−5%), but nonselectively dilated the systemic circulation at larger doses (>10−2 M). In conclusion, despite its short half-life, DEA/NO is not a selective pulmonary vasodilator compared with inhaled NO. Inhaled SNP appears to be selective to the pulmonary circulation at low doses but not at higher levels.

Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis

1998 ◽  
Vol 84 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Zenaide M. N. Quezado ◽  
Charles Natanson ◽  
Waheedullah Karzai ◽  
Robert L. Danner ◽  
Cezar A. Koev ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Bacterial Pneumonia ◽  
Ventilatory Support ◽  
Resistance Index ◽  
Pulmonary Artery Occlusion Pressure ◽  
Inhaled Nitric Oxide ◽  
E Coli ◽  
Artery Pressure ◽  
Inhaled No

Quezado, Zenaide M. N., Charles Natanson, Waheedullah Karzai, Robert L. Danner, Cezar A. Koev, Yvonne Fitz, Donald P. Dolan, Steven Richmond, Steven M. Banks, Laura Wilson, and Peter Q. Eichacker.Cardiopulmonary effects of inhaled nitric oxide in normal dogs and during E. coli pneumonia and sepsis. J. Appl. Physiol. 84(1): 107–115, 1998.—We investigated the effect of inhaled nitric oxide (NO) at increasing fractional inspired O2concentrations ([Formula: see text]) on hemodynamic and pulmonary function during Escherichia coli pneumonia. Thirty-eight conscious, spontaneously breathing, tracheotomized 2-yr-old beagles had intrabronchial inoculation with either 0.75 or 1.5 × 1010 colony-forming units/kg of E. coli 0111:B4 (infected) or 0.9% saline (noninfected) in one or four pulmonary lobes. We found that neither the severity nor distribution (lobar vs. diffuse) of bacterial pneumonia altered the effects of NO. However, in infected animals, with increasing[Formula: see text] (0.08, 0.21, 0.50, and 0.85), NO (80 parts/million) progressively increased arterial[Formula: see text] [−0.3 ± 0.6, 3 ± 1, 13 ± 4, 10 ± 9 (mean ± SE) Torr, respectively] and decreased the mean arterial-alveolar O2 gradient (0.5 ± 0.3, 4 ± 2, −8 ± 7, −10 ± 9 Torr, respectively). In contrast, in noninfected animals, the effect of NO was significantly different and opposite; NO progressively decreased mean[Formula: see text] with increasing[Formula: see text] (2 ± 1, −5 ± 3, −2 ± 3, and −12 ± 5 Torr, respectively; P < 0.05 compared with infected animals) and increased mean arterial-alveolar O2 gradient (0.3 ± 0.04, 2 ± 2, 1 ± 3, 11 ± 5 Torr; P< 0.05 compared with infected animals). In normal and infected animals alike, only at [Formula: see text]≤0.21 did NO significantly lower mean pulmonary artery pressure, pulmonary artery occlusion pressure, and pulmonary vascular resistance index (all P < 0.01). However, inhaled NO had no significant effect on increases in mean pulmonay artery pressure associated with bacterial pneumonia. Thus, during bacterial pneumonia, inhaled NO had only modest effects on oxygenation dependent on high[Formula: see text] and did not affect sepsis-induced pulmonary hypertension. These data do not support a role for inhaled NO in bacterial pneumonia. Further studies are necessary to determine whether, in combination with ventilatory support, NO may have more pronounced effects.

Hyporesponsiveness to inhaled nitric oxide in isolated, perfused lungs from endotoxin-challenged rats

1996 ◽  
Vol 271 (6) ◽  
pp. L981-L986 ◽  
Author(s):  
A. Holzmann ◽  
K. D. Bloch ◽  
L. S. Sanchez ◽  
G. Filippov ◽  
W. M. Zapol
Keyword(s):  
Nitric Oxide ◽  
Soluble Guanylate Cyclase ◽  
Sepsis Syndrome ◽  
Inhaled Nitric Oxide ◽  
Pulmonary Vasculature ◽  
Cyclic Monophosphate ◽  
Pulmonary Vasodilation ◽  
Lps Challenge ◽  
And Control ◽  
Selective Pulmonary Vasodilation

Inhaled nitric oxide (iNO) causes selective pulmonary vasodilation and improves oxygenation in patients with the adult respiratory distress syndrome (ARDS). Approximately 30% of ARDS patients fail to respond to iNO. Because sepsis syndrome often accompanies a decreased response to iNO, we investigated NO responsiveness in isolated, perfused lungs from rats exposed to lipopolysaccharide (LPS). Eighteen hours after intraperitoneal injection of 0.5 mg/kg LPS, rat lungs were isolated, perfused, and preconstricted with U-46619. Ventilation with 0.4, 4, and 40 parts per million by volume NO vasodilated LPS-pretreated lungs 75, 47, and 42% less than control lungs (P < 0.01 value differs at each concentration). The diminished vasodilatory response to iNO was associated with decreased NO-stimulated guanosine 3',5'-cyclic monophosphate (cGMP) release into the perfusate. Soluble guanylate cyclase activity did not differ in lung extracts from LPS-pretreated and control rats. LPS increased pulmonary cGMP-phosphodiesterase (PDE) activity by 40%. The PDE-sensitive cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate vasodilated lungs from LPS-pretreated rats less than lungs from control rats. In contrast, the PDE-insensitive 8-para-chlorophenylthioguanosine 3',5'-cyclic monophosphate vasodilated lungs equally from both groups. After LPS challenge, the rat pulmonary vasculature becomes hyporesponsive to iNO. Hyporesponsiveness to iNO appears partly attributable to increased pulmonary cGMP-PDE activity.

Helium inhalation enhances vasodilator effect of inhaled nitric oxide on pulmonary vessels in hypoxic dogs

2001 ◽  
Vol 280 (4) ◽  
pp. H1875-H1881 ◽  
Author(s):  
Masaki Nie ◽  
Hirosuke Kobayashi ◽  
Motoaki Sugawara ◽  
Tomoyuki Tomita ◽  
Kuniyoshi Ohara ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Characteristic Impedance ◽  
Gas Mixture ◽  
Facilitated Diffusion ◽  
Hemodynamic Parameters ◽  
Pulmonary Vasoconstriction ◽  
Vasodilatory Effect ◽  
Pulmonary Hemodynamic ◽  
Inhaled No

There are theoretical and experimental indications that the presence of He as a balance gas markedly increase the diffusion velocity of other gases contained in a gas mixture. We allowed dogs with pulmonary vasoconstriction induced by hypoxia to inhale a mixture of 5 parts per million (ppm) of nitric oxide (NO) and O2 balanced with He (NO in He) instead of N2 (NO in N2). The dilating effect of NO in He and NO in N2 on the pulmonary artery was evaluated by determining conventional pulmonary hemodynamic parameters, mean pulmonary artery (PA) pressure (MPAP), and pulmonary vascular resistance indexed to body surface area (PVRI), pulmonary impedance ( Z), and the recently developed hemodynamic index, time-corrected wave intensity (WI). The main findings in this study were as follows: 1) hypoxia increased MPAP, PVRI, Z at 0 Hz ( Z 0), Z at the first harmonics, characteristic impedance ( Z c), the reflection coefficient (Γ), and the first peak of WI; 2) NO in N2 reduced Z 0and Γ; and 3) NO in He reduced the first peak of WI and reduced Z 0 and Γ more than NO in N2. The enhanced vasodilatory effect of NO in He might be associated with facilitated diffusion of NO diluted in the gas mixture with He. In conclusion, increased efficacy of NO in He offers the possibility to reduce the inhaled NO concentration.

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