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.

Abstract 12177: Inhaled Nitric Oxide During Cardiopulmonary Resuscitation Improves Functional Outcome and Increases 7-Day-Survival After Prolonged Cardiac Arrest in Rats

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Anne Brücken ◽  
Christian Bleilevens ◽  
Matthias Derwall ◽  
Michael Fries
Keyword(s):  
Nitric Oxide ◽  
Cardiac Arrest ◽  
Cardiopulmonary Resuscitation ◽  
Functional Outcome ◽  
Statistical Significance ◽  
Spontaneous Circulation ◽  
Left Ventricular ◽  
Inhaled Nitric Oxide ◽  
Sprague Dawley ◽  
Pulmonary Vasodilator

Introduction: Precordial compressions during cardiac arrest (CA) increase pulmonary vascular resistance (PVR), potentially impeding survival by limiting left ventricular preload. Although used as selective pulmonary vasodilator there is accumulating evidence that inhaled nitric oxide (iNO) also attenuates I/R injury. Hypothesis: Applying iNO during cardiopulmonary resuscitation (CPR) increases resuscitation rates and improves functional outcome after cardiac arrest in rats. Methods: Thirty male Sprague-Dawley rats were subjected to 10 mins of CA and 3 mins of CPR. Animals were randomized to receive either 20 ppm or 40 ppm iNO during CPR until 30 mins after ROSC (return of spontaneous circulation) or no iNO treatment. For all animals a neurological deficit score (NDS) was calculated daily for seven days following the experiment. Results: Inhalation of 20 ppm iNO increased ROSC rates in comparison to animals treated with 40 ppm or without iNO treatment, however this failed to reach statistical significance (control: 7/10; 20ppm iNO: 10/10; 40ppm iNO 6/10). 20 ppm iNO significantly decreased time to ROSC, resulting in a significant reduction of post-arrest lactate levels. Also, significantly higher mean arterial pressures in comparison to control animals were observed. Furthermore, 20 ppm iNO resulted in a significantly higher seven-day-survival in comparison to controls (control: 4/10; 20 ppm iNO: 10/10). All iNO treated animals showed better neurological outcomes, being significant in animals treated with 20 ppm iNO on postoperative day 2- 7. Conclusions: Our study demonstrates that 20 ppm but not 40 ppm iNO during CPR significantly decreases time to ROSC. Furthermore, significantly better seven-day-survival and neurological outcome was noted for 20 ppm iNO in comparison to controls.

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 20: Peripheral Intravenous Analysis Detects Return of Spontaneous Circulation Without Interruption of Chest Compressions in a Rat Model of Cardiopulmonary Resuscitation

Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Claudius Balzer ◽  
Franz J Baudenbacher ◽  
Antonio Hernandez ◽  
Michele M Salzman ◽  
Matthias L Riess ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Cardiopulmonary Resuscitation ◽  
Chest Compression ◽  
Venous Pressure ◽  
Fold Increase ◽  
Spontaneous Circulation ◽  
Arterial Line ◽  
Chest Compressions ◽  
Waveform Data ◽  
Return Of Spontaneous Circulation

Introduction: A higher chest compression fraction (CCF) or percentage of time providing chest compressions is associated with improved survival after cardiac arrest (CA). Pauses in chest compression duration during cardiopulmonary resuscitation (CPR) to palpate a pulse can reduce the CCF. Peripheral Intravenous Analysis (PIVA) is a novel method for determining cardiac and volume status using waveforms from a standard peripheral intravenous (IV) line. We hypothesize that PIVA will demonstrate the onset of return of spontaneous circulation (ROSC) without interruption of CPR. Methods: Eight Zucker Diabetic Fatty (ZDF) rats (4 lean, 4 diabetic) were intubated, ventilated, and cannulated with a 24g IV in the tail vein and a 22g IV in the femoral artery, each connected to a TruWave pressure transducer. Mechanical ventilation was discontinued to achieve CA. After 8 minutes, CPR began with mechanical ventilation, IV epinephrine, and chest compressions using 1.5 cm at 200 times per minute until mean arterial pressure (MAP) increased to 120 mmHg per arterial line. All waveforms were recorded and analyzed in LabChart. PIVA was measured using a Fourier transform of the peripheral venous waveform. Data are mean ± SD. Statistics: Unpaired student’s t-test (two-tailed), α = 05. Results: CA and ROSC were achieved in all 8 rats. Within 1 minute of CPR, there was a 70 ± 35 fold increase/decrease in PIVA during CPR that was temporally associated with ROSC. Within 8 ± 13 seconds of a reduction in PIVA, there was a rapid increase in end-tidal CO 2 . In all rats, ROSC occurred within 38 ± 9 seconds of the maximum PIVA value. Peripheral venous pressure decreased by 1.2 ± 0.9 mmHg during resuscitation and ROSC, which was not significant different at p=0.05. Conclusion: In this pilot study, PIVA detected ROSC without interrupting CPR. Use of PIVA may obviate the need pause CPR for pulse checks, and may result in a higher CCF and survival. Future studies will focus on PIVA and CPR efficacy.

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.

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.

Association of Plasma Cell-Free Hemoglobin with Physiological Measures of Nitric Oxide Responsiveness and Estimated Pulmonary Artery Systolic Pressure: Requirement for Rigorously Optimized Blood Processing Variables

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3253-3253
Author(s):  
Laurel G. Mendelsohn ◽  
Susan Yuditskaya ◽  
Xunde Wang ◽  
Wasnard Victor ◽  
Katherine Corbin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Right Heart Catheterization ◽  
Heart Catheterization ◽  
Free Hemoglobin ◽  
Artery Pressure ◽  
Plasma Hemoglobin ◽  
Processing Variables

Abstract Abstract 3253 Background: Accurate plasma hemoglobin (PHb) measurements are needed to investigate a model proposing a link between intravascular hemolysis and decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD). Artifactual hemolysis hypothetically can produce excessive noise that might obscure the signal and lead to misinterpretation of data. We systematically studied possible blood processing variables that could cause artifactual hemolysis to obscure in vivo levels of free hemoglobin in adults with SCD. Methods: We systematically compared the effects on PHb measured by ELISA of anticoagulant type, Vacutainer materials and processing time on the same blood specimens from healthy controls and adults with SCD divided into aliquots that were then processed using a variety of in vitro conditions. We analyzed the results of PHb measurements from archived specimens from 467 SCD patients. We evaluated in greater detail plasma specimens collected and processed at bedside from 44 patients with SCD under optimal conditions: drawn from indwelling wide-bore brachial artery catheters by minimal negative pressure into heparinized syringes, gently transferred to tubes for centrifugation within 5 minutes, evaluating the associations of PHb levels from these optimally processed samples with relevant in vivo physiological measurements. Results: Analysis of specimens from healthy control subjects (n=10) and adults with SCD (n=10) for each experiment, split into aliquots to test each variable under defined conditions yielded significant evidence indicating that: (1) arterial catheter syringe specimens are superior to conventional Vacutainer venipuncture specimens; (2) heparin is superior to EDTA anticoagulant; (3) glass tubes are superior to plastic tubes; (4) processing in 2 hours or less is superior to longer processing times. Comparison of 467 archived EDTA plasma specimens processed under comparably variable conditions provided results consistent with the bench top results, confirming the importance of these processing variables on research specimens. Conventional venipuncture EDTA Vacutainer tubes with conventional processing yielded median PHb levels four-fold that of arterial catheter heparin syringe specimens processed at bedside, suggesting that on average 75% of the PHb in conventional specimens may represent background noise and only 25% of the PHb level may represent in vivo free hemoglobin. Blood specimens were collected and processed by the optimal conditioned defined by the preceding experiments from 44 adults with sickle cell anemia. This set of specimens yielded a median PHb level of 6.07μM (CI95=5.27–7.03μM). PHb correlated significantly with blunting of vasodilation in vivo after brachial artery infusion of each of three graded doses of the NO donor sodium nitroprusside (SNP), an indicator of vascular NO responsiveness; at doses of 0.8μg/min(r=−0.46 p=0.0022), 1.6μg/min (r=−0.41, p=0.0082), and 3.2μg/min (r=−0.46, p=0.0024). Quartile analysis revealed a significant difference in forearm blood flow response across all doses of SNP among the highest, middle, and lowest PHb quartiles (p=0.0386). PHb also correlated significantly with tricuspid regurgitant velocity (R=0.37, p=0.0147), suggesting a significant association with Doppler echocardiography estimates of pulmonary artery pressure. A limited number of patients from this specimen pool (n=7) subsequently underwent clinically indicated right heart catheterization. There was a trend in this small subset correlating PHb with mean pulmonary artery pressure (r=0.61, p=0.1482). Conclusions: Plasma hemoglobin levels collected and processed under optimal conditions show statistically significant associations with in vivo physiological measures of nitric oxide responsiveness and echocardiographically estimated pulmonary artery pressure, with supportive trends from right heart catheterization in a limited subgroup of patients with SCD. This supports a role for plasma hemoglobin as a biomarker of nitric oxide resistance and pulmonary hypertension in SCD. Conventional phlebotomy into Vacutainer tubes introduces a high background level of artifactual ex vivo hemolysis in SCD specimens that is capable of obscuring these associations, especially if processing is delayed 2 hours or more. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Beneficial Effects of Nitric Oxide on Outcomes after Cardiac Arrest and Cardiopulmonary Resuscitation in Hypothermia-treated Mice

2014 ◽  
Vol 120 (4) ◽  
pp. 880-889 ◽  
Author(s):  
Kotaro Kida ◽  
Kazuhiro Shirozu ◽  
Binglan Yu ◽  
Joseph B. Mandeville ◽  
Kenneth D. Bloch ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cardiac Arrest ◽  
Cerebral Blood Flow ◽  
Brain Injury ◽  
Cardiopulmonary Resuscitation ◽  
Inhaled Nitric Oxide ◽  
Wild Type ◽  
Beneficial Effects ◽  
Endogenous Nitric Oxide

Abstract Background: Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Although nitric oxide prevents organ injury induced by ischemia and reperfusion, role of nitric oxide during TH after CPR remains unclear. In this article, the authors examined the impact of endogenous nitric oxide synthesis on the beneficial effects of hypothermia after CA/CPR. The authors also examined whether or not inhaled nitric oxide during hypothermia further improves outcomes after CA/CPR in mice treated with TH. Methods: Wild-type mice and mice deficient for nitric oxide synthase 3 (NOS3−/−) were subjected to CA at 37°C and then resuscitated with chest compression. Body temperature was maintained at 37°C (normothermia) or reduced to 33°C (TH) for 24 h after resuscitation. Mice breathed air or air mixed with nitric oxide at 10, 20, 40, 60, or 80 ppm during hypothermia. To evaluate brain injury and cerebral blood flow, magnetic resonance imaging was performed in wild-type mice after CA/CPR. Results: Hypothermia up-regulated the NOS3-dependent signaling in the brain (n = 6 to 7). Deficiency of NOS3 abolished the beneficial effects of hypothermia after CA/CPR (n = 5 to 6). Breathing nitric oxide at 40 ppm improved survival rate in hypothermia-treated NOS3−/− mice (n = 6) after CA/CPR compared with NOS3−/− mice that were treated with hypothermia alone (n = 6; P &lt; 0.05). Breathing nitric oxide at 40 (n = 9) or 60 (n = 9) ppm markedly improved survival rates in TH-treated wild-type mice (n = 51) (both P &lt; 0.05 vs. TH-treated wild-type mice). Inhaled nitric oxide during TH (n = 7) prevented brain injury compared with TH alone (n = 7) without affecting cerebral blood flow after CA/CPR (n = 6). Conclusions: NOS3 is required for the beneficial effects of TH. Inhaled nitric oxide during TH remains beneficial and further improves outcomes after CA/CPR. Nitric oxide breathing exerts protective effects after CA/CPR even when TH is ineffective due to impaired endogenous nitric oxide production.

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