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.

scholarly journals Progressive dysfunction of nitric oxide synthase in a lamb model of chronically increased pulmonary blood flow: a role for oxidative stress

2008 ◽  
Vol 295 (5) ◽  
pp. L756-L766 ◽  
Author(s):  
Peter E. Oishi ◽  
Dean A. Wiseman ◽  
Shruti Sharma ◽  
Sanjiv Kumar ◽  
Yali Hou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Lung Tissue ◽  
Pulmonary Blood Flow ◽  
Artery Pressure ◽  
Oxide Synthase ◽  
Inhaled No

Cardiac defects associated with increased pulmonary blood flow result in pulmonary vascular dysfunction that may relate to a decrease in bioavailable nitric oxide (NO). An 8-mm graft (shunt) was placed between the aorta and pulmonary artery in 30 late gestation fetal lambs; 27 fetal lambs underwent a sham procedure. Hemodynamic responses to ACh (1 μg/kg) and inhaled NO (40 ppm) were assessed at 2, 4, and 8 wk of age. Lung tissue nitric oxide synthase (NOS) activity, endothelial NOS (eNOS), neuronal NOS (nNOS), inducible NOS (iNOS), and heat shock protein 90 (HSP90), lung tissue and plasma nitrate and nitrite (NOx), and lung tissue superoxide anion and nitrated eNOS levels were determined. In shunted lambs, ACh decreased pulmonary artery pressure at 2 wk ( P < 0.05) but not at 4 and 8 wk. Inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). In control lambs, ACh and inhaled NO decreased pulmonary artery pressure at each age ( P < 0.05). Total NOS activity did not change from 2 to 8 wk in control lambs but increased in shunted lambs (ANOVA, P < 0.05). Conversely, NOxlevels relative to NOS activity were lower in shunted lambs than controls at 4 and 8 wk ( P < 0.05). eNOS protein levels were greater in shunted lambs than controls at 4 wk of age ( P < 0.05). Superoxide levels increased from 2 to 8 wk in control and shunted lambs (ANOVA, P < 0.05) and were greater in shunted lambs than controls at all ages ( P < 0.05). Nitrated eNOS levels were greater in shunted lambs than controls at each age ( P < 0.05). We conclude that increased pulmonary blood flow results in progressive impairment of basal and agonist-induced NOS function, in part secondary to oxidative stress that decreases bioavailable NO.

Sildenafil therapy for neonatal and childhood pulmonary hypertensive vascular disease

2010 ◽  
Vol 21 (2) ◽  
pp. 187-193 ◽  
Author(s):  
Tilman Humpl ◽  
Janette T. Reyes ◽  
Simon Erickson ◽  
Ruth Armano ◽  
Helen Holtby ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Artery ◽  
Right Ventricular ◽  
Pressure Ratio ◽  
Systolic Pressure ◽  
Resistance Index ◽  
Pulmonary Artery Hypertension ◽  
Inhaled Nitric Oxide ◽  
Drug Study

AbstractObjectivesWe hypothesised that sildenafil would improve hemodynamics in children with pulmonary hypertension and attenuate rebound pulmonary hypertension after inhaled nitric oxide withdrawal.Patients and methodsWe undertook an open-label, single-drug study of sildenafil in patients under 5 years of age with either symptomatic or rebound pulmonary hypertension following inhaled nitric oxide withdrawal.ResultsWe recruited 25 patients (median age 180 days, 10–1790) to receive sildenafil. The median right ventricular to systemic systolic blood pressure ratio before sildenafil therapy was 1.0 (0.5–1.4) and decreased to 0.5 (with a range from 0.3 to 1.3; p = 0.0002). In five patients the baseline pulmonary vascular resistance index was 10 (7.1–13.6) Wood units metre square and decreased to 5.8 (2.7–15.6) Wood units metre square (p = 0.04) at 6 months. Ten patients were treated with sildenafil for a median of 34 days (9–499) until resolution of pulmonary artery hypertension and continue to do well. Six patients continued sildenafil therapy for a median of 1002 days (384–1574) with improvement but without resolution of pulmonary hypertension. There was no change in serum creatinine, urea, liver function tests, or platelet count. In 15 patients sildenafil abolished rebound pulmonary artery hypertension following withdrawal of inhaled nitric oxide. Median right ventricular pressure to systemic systolic pressure ratio decreased from 1.0 (0.8–1.4) during nitric oxide withdrawal to 0.4 (0.3–0.8) p = 0.006 after pre-treatment with sildenafil.ConclusionIn children under 5 years of age with severe pulmonary hypertension, sildenafil therapy resulted in prolonged hemodynamic improvements without adverse effects. Sildenafil attenuated rebound pulmonary hypertension after withdrawal of inhaled nitric oxide.

scholarly journals Correlation of inhaled nitric-oxide induced reduction of pulmonary artery pressure and vascular changes

2002 ◽  
Vol 20 (1) ◽  
pp. 52-58 ◽  
Author(s):  
B.H. Jiang ◽  
J. Maruyama ◽  
A. Yokochi ◽  
H. Amano ◽  
Y. Mitani ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Inhaled Nitric Oxide ◽  
Vascular Changes ◽  
Artery Pressure

Abstract 267: Inhaled Nitric Oxide Lowers Pulmonary Artery Pressure During Cardiopulmonary Resuscitation but Does Not Increase Survival in a Model of Prolonged Cardiac Arrest in Pigs

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Matthias Derwall ◽  
Andreas Ebeling ◽  
Anne Brücken ◽  
Michael Fries
Keyword(s):  
Nitric Oxide ◽  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Spontaneous Circulation ◽  
Inhaled Nitric Oxide ◽  
Arterial Line ◽  
Chest Compressions ◽  
Artery Pressure

Introduction: We have previously shown that thoracic chest compressions during cardiac arrest (CA) result in elevated pulmonary vascular resistance (PVR), potentially impeding a return of spontaneous circulation (ROSC) by limiting circulation. Hypothesis: Applying inhaled nitric oxide (iNO) will lower PVR during cardiopulmonary resuscitation (CPR). Methods: 8 pigs were instrumented with an arterial line and a pulmonary artery catheter. CA was electrically induced and left untreated for 10 minutes before CPR was performed employing mechanical chest compressions and mechanical ventilation. Animals were randomized to either receive 20ppm of iNO (n = 3, iNO) or 100% Oxygen (n = 5, Control) during CPR. After 6 minutes of CPR, defibrillation was attempted. When no ROSC was achieved, chest compressions were restarted and continued for up to 30 minutes. Results: Mean pulmonary artery pressure (MPAP) rose significantly from 9 ± 4 following 10 minutes of VF to 21 ± 7 mmHg following 1 minute of CPR in Control animals (p=0.01). Animals receiving iNO showed a significantly lesser increase in MPAP from 5 ± 1 following 10 minutes of VF to 8 ± 3 mmHg following 1 minute of CPR (p=0.18). While MPAP did not differ on baseline or during 10 minutes of VF, iNO treatment resulted in significantly lower MPAP values averaged over the first 6 minutes of CPR (10 ± 1 vs. 22 ± 1 mmHg, p<0.01 ; see Figure ; * indicates p<0.01 for MPAP iNO vs. Control). This was reflected by similar changes in PVR, which remained significantly lower in iNO treated animals during CPR (80 ± 9 vs. 188 ± 17 dyn x sec x cm-5, p<0.01). While no animal achieved ROSC in the iNO group, two of the five control animals could be successfully resuscitated. Conclusion: Ventilation with 20ppm nitric oxide during CPR reduces MPAP and PVR following prolonged CA, but does not improve survival in these preliminary experiments. Expanding the sample size will be necessary to determine potential impact of this intervention on survival or neurocognitive outcome.

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.

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.

Inhaled nitric oxide inhibits NOS activity in lambs: potential mechanism for rebound pulmonary hypertension

1999 ◽  
Vol 277 (5) ◽  
pp. H1849-H1856 ◽  
Author(s):  
Stephen M. Black ◽  
R. Scott Heidersbach ◽  
D. Michael McMullan ◽  
Janine M. Bekker ◽  
Michael J. Johengen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Pulmonary Vascular Resistance ◽  
Vascular Resistance ◽  
Inhaled Nitric Oxide ◽  
Protein Levels ◽  
Acute Withdrawal ◽  
Inhaled No

Life-threatening increases in pulmonary vascular resistance have been noted on acute withdrawal of inhaled nitric oxide (NO), although the mechanisms remain unknown. In vitro data suggest that exogenous NO exposure inhibits endothelial NO synthase (NOS) activity. Thus the objectives of this study were to determine the effects of inhaled NO therapy and its acute withdrawal on endogenous NOS activity and gene expression in vivo in the intact lamb. Six 1-mo-old lambs were mechanically ventilated and instrumented to measure vascular pressures and left pulmonary blood flow. Inhaled NO (40 ppm) acutely decreased left pulmonary vascular resistance by 27.5 ± 4.7% ( P < 0.05). This was associated with a 207% increase in plasma cGMP concentrations ( P < 0.05). After 6 h of inhaled NO, NOS activity was reduced to 44.3 ± 5.9% of pre-NO values ( P < 0.05). After acute withdrawal of NO, pulmonary vascular resistance increased by 52.1 ± 11.6% ( P < 0.05) and cGMP concentrations decreased. Both returned to pre-NO values within 60 min. One hour after NO withdrawal, NOS activity increased by 48.4 ± 19.1% to 70% of pre-NO values ( P < 0.05). Western blot analysis revealed that endothelial NOS protein levels remained unchanged throughout the study period. These data suggest a role for decreased endogenous NOS activity in the rebound pulmonary hypertension noted after acute withdrawal of inhaled NO.

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