Hemodynamic effects of nitric oxide synthase inhibition before and after cardiac arrest in infant piglets

1998 ◽  
Vol 274 (4) ◽  
pp. H1378-H1385 ◽  
Author(s):  
Charles L. Schleien ◽  
John W. Kuluz ◽  
Barry Gelman
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cardiac Arrest ◽  
Cerebral Blood Flow ◽  
Cerebral Metabolism ◽  
Lactate Production ◽  
No Synthase ◽  
Metabolic Effects ◽  
Successful Resuscitation ◽  
Baseline Levels

Using infant piglets, we studied the effects of nonspecific inhibition of nitric oxide (NO) synthase by N G-nitro-l-arginine methyl ester (l-NAME; 3 mg/kg) on vascular pressures, regional blood flow, and cerebral metabolism before 8 min of cardiac arrest, during 6 min of cardiopulmonary resuscitation (CPR), and at 10 and 60 min of reperfusion. We tested the hypotheses that nonspecific NO synthase inhibition 1) will attenuate early postreperfusion hyperemia while still allowing for successful resuscitation after cardiac arrest, 2) will allow for normalization of blood flow to the kidneys and intestines after cardiac arrest, and 3) will maintain cerebral metabolism in the face of altered cerebral blood flow after reperfusion. Before cardiac arrest, l-NAME increased vascular pressures and cardiac output and decreased blood flow to brain (by 18%), heart (by 36%), kidney (by 46%), and intestine (by 52%) compared with placebo. During CPR, myocardial flow was maintained in all groups to successfully resuscitate 24 of 28 animals [ P value not significant (NS)]. Significantly,l-NAME attenuated postresuscitation hyperemia in cerebellum, diencephalon, anterior cerebral, and anterior-middle watershed cortical brain regions and to the heart. Likewise, cerebral metabolic rates of glucose (CMRGluc) and of lactate production (CMRLac) were not elevated at 10 min of reperfusion. These cerebral blood flow and metabolic effects were reversed byl-arginine. Flows returned to baseline levels by 60 min of reperfusion. Kidney and intestinal flow, however, remained depressed throughout reperfusion in all three groups. Thus nonspecific inhibition of NO synthase did not adversely affect the rate of resuscitation from cardiac arrest while attenuating cerebral and myocardial hyperemia. Even though CMRGluc and CMRLac early after resuscitation were decreased, they were maintained at baseline levels. This may be clinically advantageous in protecting the brain and heart from the damaging effects of hyperemia, such as blood-brain barrier disruption.

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 < 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 < 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.

Nitric oxide, prostaglandins, and impaired cerebral blood flow autoregulation in group B streptococcal neonatal meningitis

2000 ◽  
Vol 78 (3) ◽  
pp. 217-227 ◽  
Author(s):  
Carmen Mertineit ◽  
Jacqueline Samlalsingh-Parker ◽  
Maria Glibetic ◽  
Ginette Ricard ◽  
Francisco JD Noya ◽  
...  
Keyword(s):  
Gene Expression ◽  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Early Onset ◽  
No Synthase ◽  
Neonatal Meningitis ◽  
Cerebrovascular Autoregulation ◽  
Upper Limit ◽  
Group B

Impaired autoregulation of cerebral blood flow (CBF) contributes to CNS damage during neonatal meningitis. We tested (i) the hypothesis that cerebrovascular autoregulation is impaired during early onset group B streptococcal (GBS) meningitis, (ii) whether this impairment is regulated by vasoactive mediators such as prostaglandins and (or) nitric oxide (NO), and (iii) whether this impairment is preventable by specific and (or) nonspecific inhibitors: dexamethasone, ibuprofen, and Nω-nitro-L-arginine, a NO inhibitor. Sterile saline or 109colony-forming units (cfu) of heat-killed GBS was injected into the cerebral ventricle of newborn piglets. CBF autoregulation was determined by altering cerebral perfusion pressure (CPP) with balloon-tipped catheters placed in the aorta. GBS produced a narrow range of CBF autoregulation due to an impairment at the upper limit of CPP. We report that in vivo in the early stages (first 2 h) of induced GBS inflammation (i) GBS impairs the upper limit of cerebrovascular autoregulation; (ii) ibuprofen, dexamethasone, and Nω-nitro-L-arginine not only prevent this GBS-induced autoregulatory impairment but improve the range of cerebrovascular autoregulation; (iii) these autoregulatory changes do not involve circulating cerebral prostanoids; and (iv) the observed changes correlate with the induction of NO synthase gene expression. Thus, acute early onset GBS-induced impairment of the upper limit of CBF autoregulation can be correlated with increases of NO synthase production, suggesting that NO is a vasoactive mediator of CBF.Key words: cerebrovascular autoregulation, group B Streptococcus, neonatal meningitis, anti-inflammatory agents, prostanoids, nitric oxide synthase, gene expression, nitric oxide.

Abstract 102: Inhaled Nitric Oxide Mitigates Pulmonary Hypertension and Improves Cerebral Hemodynamics During Prolonged Cardiopulmonary Pesuscitation in a Swine Model of Pediatric Cardiac Arrest

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Constantine D Mavroudis ◽  
Ryan W Morgan ◽  
Tiffany S Ko ◽  
Marco M Hefti ◽  
William P Landis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Pulmonary Hypertension ◽  
Cardiac Arrest ◽  
Cerebral Blood Flow ◽  
Pulmonary Artery ◽  
Pulmonary Artery Pressure ◽  
Systemic Hemodynamics ◽  
Swine Model ◽  
Pulmonary Vasodilation

Introduction: Pulmonary hypertension may play a role in preventing ROSC during prolonged CPR. Targeted pulmonary vasodilation with inhaled nitric oxide (iNO) during CPR may improve pulmonary blood flow and improve outcomes. The purpose of this study was to study the effects of iNO in a randomized, blinded, placebo controlled, pediatric swine model of asphyxial cardiac arrest. Hypothesis: Animals treated with iNO will have lower pulmonary artery pressure, improved systemic hemodynamics, and increased cerebral blood flow during prolonged CPR compared to control. Methods: Four-week-old piglets (n=10) that underwent seven minutes of asphyxia, induction of VF, and 10 minutes of CPR were randomized to either iNO (20 ppm) or placebo in a blinded fashion starting one min into CPR and needed more than 1 defibrillation attempt. Defibrillation was attempted after 10 minutes of CPR. Animals that did not achieve ROSC by 20 minutes were euthanized. Invasive pulmonary and systemic hemodynamics, and both invasive and noninvasive cerebral hemodynamics were continuously measured. Data described as mean ± SD and compared using a generalized estimating equation regression model. Results: All 5 iNO-treated animals and 2/5 placebo-treated animals achieved ROSC. Those treated with iNO had lower mean pulmonary artery pressures (29.5 ± 9.1 vs. 48.3 ± 5.6 mmHg, p=0.04); higher mean aortic pressures (51.9 ± 6.4 vs. 35.5 ± 4.4 mmHg, p=0.01); higher cerebral blood flow (invasive: 230.4 ± 57.4 vs. 28.7 ± 42.1 % baseline, p<0.001; noninvasive: 58.4 ± 10.9 vs. 32.4 ± 8.1 % baseline, p=0.02); and higher cerebral tissue oxygenation (invasive: 33.1 ± 13.0 vs. 1.2 ± 9.8 mmHg, p=0.01; noninvasive: 38.0 ± 4.2 vs. 26.2 ± 3.1%, p=0.005) compared with placebo. Conclusions: Treatment with iNO during prolonged CPR results in lower pulmonary artery pressure, improved systemic hemodynamics, and increased cerebral blood flow and oxygenation. Pulmonary vasodilation may have an important role during prolonged CPR for asphyxial cardiac arrests.

scholarly journals Therapeutic hypothermia promotes cerebral blood flow recovery and brain homeostasis after resuscitation from cardiac arrest in a rat model

2018 ◽  
Vol 39 (10) ◽  
pp. 1961-1973 ◽  
Author(s):  
Qihong Wang ◽  
Peng Miao ◽  
Hiren R Modi ◽  
Sahithi Garikapati ◽  
Raymond C Koehler ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cardiac Arrest ◽  
Cerebral Blood Flow ◽  
Therapeutic Hypothermia ◽  
Neurological Outcome ◽  
Spontaneous Circulation ◽  
Early Application ◽  
Information Quantity ◽  
Multiple Parameters ◽  
Baseline Levels

Laboratory and clinical studies have demonstrated that therapeutic hypothermia (TH), when applied as soon as possible after resuscitation from cardiac arrest (CA), results in better neurological outcome. This study tested the hypothesis that TH would promote cerebral blood flow (CBF) restoration and its maintenance after return of spontaneous circulation (ROSC) from CA. Twelve Wistar rats resuscitated from 7-min asphyxial CA were randomized into two groups: hypothermia group (7 H, n = 6), treated with mild TH (33–34℃) immediately after ROSC and normothermia group (7 N, n = 6,37.0 ± 0.5℃). Multiple parameters including mean arterial pressure, CBF, electroencephalogram (EEG) were recorded. The neurological outcomes were evaluated using electrophysiological (information quantity, IQ, of EEG) methods and a comprehensive behavior examination (neurological deficit score, NDS). TH consistently promoted better CBF restoration approaching the baseline levels in the 7 H group as compared with the 7 N group. CBF during the first 5–30 min post ROSC of the two groups was 7 H:90.5% ± 3.4% versus 7 N:76.7% ± 3.5% ( P < 0.01). Subjects in the 7 H group showed significantly better IQ scores after ROSC and better NDS scores at 4 and 24 h. Early application of TH facilitates restoration of CBF back to baseline levels after CA, which in turn results in the restoration of brain electrical activity and improved neurological outcome.

Cerebral Metabolism of Nitric Oxide during Retrograde Cerebral Perfusion

2002 ◽  
Vol 10 (3) ◽  
pp. 223-227 ◽  
Author(s):  
Katsuhito Ueno ◽  
Shinichi Takamoto ◽  
Takeshi Miyairi ◽  
Tetsuro Morota ◽  
Ko Shibata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Cerebral Perfusion ◽  
Cerebral Metabolism ◽  
Oxidation Products ◽  
Retrograde Cerebral Perfusion ◽  
Ph Stat ◽  
The Brain

The aim of this study was to determine whether alpha- or pH-stat protects the brain during deep hypothermic retrograde cerebral perfusion. Fifteen anesthetized dogs on cardiopulmonary bypass were cooled to 18°C under alpha-stat and underwent retrograde cerebral perfusion for 90 minutes under alpha-stat or pH-stat, or underwent antegrade cardiopulmonary bypass under alpha-stat as the control. Cerebral blood flow of the cortex was monitored and serial analyses of blood gases and total nitric oxide oxidation products made. Cerebral blood flow and cerebral metabolic rate for oxygen were significantly higher and plasma levels of nitric oxide oxidation products in the outflow from the brain were significantly lower in retrograde cerebral perfusion under pH-stat than under alpha-stat. This study shows that reduced levels of nitric oxide oxidation products may protect against neuronal damage induced by nitric oxide and that increased cerebral blood flow under pH-stat may lead to a reduction of nitric oxide oxidation products. Under retrograde cerebral perfusion, pH-stat is thus better than alpha-stat for protecting the brain.

scholarly journals Local NADPH—Diaphorase Neurons Innervate Pial Arteries and Lie Close or Project to Intracerebral Blood Vessels: A Possible Role for Nitric Oxide in the Regulation of Cerebral Blood Flow

1993 ◽  
Vol 13 (6) ◽  
pp. 978-984 ◽  
Author(s):  
Carmen Estrada ◽  
Elisa Mengual ◽  
Carmen González
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Blood Vessels ◽  
Neuronal Cell ◽  
Histochemical Staining ◽  
Nerve Fibers ◽  
No Synthase ◽  
Nadph Diaphorase ◽  
Pial Arteries

Electrical stimulation of perivascular nerves induced a relaxation of endothelium-denuded cat pial arteries that was significantly reduced by nitric oxide (NO) synthase inhibition, indicating that NO was involved in the neurogenic relaxation of these vessels. Histochemical staining of the pial arteries for NADPH-diaphorase (NADPH-d), used as a marker for NO synthase, showed positive nerve fibers in the adventitial layer. Interestingly, in some restricted areas stained neuronal cell bodies were also observed. These neurons were scattered or distributed in small groups in a ganglion-like manner, and they sent fibers to the vessel wall. No NADPH-d-positive nerve fibers or cell bodies were detected in forelimb, pulmonary, or coronary arteries. Within the brain parenchyma, blood vessels also showed positive fibers around their walls. These fibers were organized in a branching pattern and presented varicosities. NADPH-d-positive neurons were found in the proximity of the intracerebral vascular profiles, sending processes to the vessels and/or being directly apposed to their wall. The neurovascular contacts were preferentially located close to the interface between the cerebral cortex and white matter. The anatomical relationship between NADPH-d-positive neurons and fibers and the cerebral blood vessels, together with the participation of NO in the neurogenic relaxation of pial arteries, suggests that NO is involved in the regulation of cerebral blood flow.

scholarly journals Augmentation of Blood Flow through Cerebral Collaterals by Inhibition of Nitric Oxide Synthase

1994 ◽  
Vol 14 (5) ◽  
pp. 704-714 ◽  
Author(s):  
Michael G. Muhonen ◽  
Donald D. Heistad ◽  
Frank M. Faraci ◽  
Christopher M. Loftus
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Arterial Pressure ◽  
Aortic Pressure ◽  
No Synthase ◽  
Artery Pressure ◽  
Pial Artery ◽  
Anesthetized Dogs ◽  
Oxide Synthase

We examined the influence of nitric oxide (NO) on normal and collateral cerebral blood flow after occlusion of the middle cerebral artery (MCA). Effects of NG-nitro-l-arginine (nitroarginine), an inhibitor of NO synthase, were examined during normotension and hypotension (arterial pressure, 50 mm Hg) in 49 anesthetized dogs. Following a craniotomy, a branch of the MCA was cannulated, and collateral-dependent tissue was identified using the shadow-flow technique. Regional cerebral blood flow was measured with microspheres, and pial artery pressure was measured with a micropipette. Intravenous nitroarginine reduced blood flow to normal cerebrum by approximately 40% (p < 0.05) during normotension and hypotension, with aortic pressure maintained constant after nitroarginine administration. Injection of nitroarginine during hypotension, without control of pressor effects, increased aortic and pial artery pressure approximately twofold. Concurrently, blood flow to normal cerebrum decreased (p < 0.05), while flow to collateral-dependent cerebrum increased (p < 0.05). Phenylephrine was infused during hypotension to increase arterial pressure to values similar to those achieved following nitroarginine. Blood flow to collateral-dependent cerebrum increased (p < 0.05), but flow to normal cerebrum was not altered during infusion of phenylephrine. Thus, inhibition of NO synthase during hypotension increases arterial pressure, decreases blood flow to normal cerebrum, and increases blood flow to collateral-dependent cerebrum. Phenylephrine also increases perfusion pressure and blood flow to collateral-dependent cerebrum, but in contrast to nitroarginine, it does not redistribute blood flow from normal cerebrum.

Coupling of cerebral blood flow to neuronal activation: role of adenosine and nitric oxide

1994 ◽  
Vol 267 (1) ◽  
pp. H296-H301 ◽  
Author(s):  
U. Dirnagl ◽  
K. Niwa ◽  
U. Lindauer ◽  
A. Villringer
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Receptor Antagonist ◽  
Barrel Cortex ◽  
No Synthase ◽  
Neuronal Activation ◽  
Whisker Stimulation ◽  
Relationship Of

We studied the role and relationship of the putative mediators of coupling of cerebral blood flow (CBF) and neuronal activation, adenosine (Ado) and nitric oxide (NO). Topical brain application over the whisker barrel cortex of anesthetized rats (n = 24) of the Ado receptor antagonist theophylline (Theo, 5 x 10(-5) M) for 30 min reduced the CBF response to deflection of the contralateral whiskers from 17.9 +/- 3.0% of baseline to 10.6 +/- 2.7% (P < 0.05). Coapplication of Theo (5 x 10(-5) M) and the NO synthase blocker N omega-nitro-L-arginine (L-NNA, 10(-3) M) for 30 min led to a further reduction in the CBF response to whisker stimulation to 7.5 +/- 1.3% (P < 0.05 compared with Theo alone). The CBF effect of sodium nitroprusside (10(-5) M) was not affected by Theo-L-NNA coapplication (122 +/- 25 vs. 140 +/- 25%, n = 5). Application of adenosine deaminase (1 U/ml, n = 5) reduced the CBF response to whisker stimulation from 18.2 +/- 0.7 to 10.7 +/- 1.9% (P < 0.05). Superfusion of L-NNA (10(-3) M, 30 min, n = 7) attenuated the CBF response to application of Ado (10(-4) M) from 39.4 +/- 10.4 to 22.9 +/- 10.5% (P < 0.05). N omega-nitro-D-arginine did not affect the CBF response to Ado (n = 5). We conclude that 1) Ado is involved in coupling of CBF to neuronal activation, 2) NO is involved in this response as well, and 3) there is an interaction between the vasodilator pathways of Ado and NO.

Sign in / Sign up

Export Citation Format

Share Document