Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets

Albert, Johanna; Harbut, Piotr; Zieliński, Stanisław; Ryniak, S.; Gillis-Hægerstrand, Caroline; Lindwall, Robert; Solski, L.; Lundberg, Jon O.; Svensson, Jan; Goździk, Waldemar

doi:10.1007/s00134-007-0666-3

Cited by 17 publications

(13 citation statements)

References 37 publications

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“…Impaired platelet function is commonly observed in sepsis. All these observations underscore the difficulty in extrapolating clinical bleeding tendency from different studies, and may explain some of the present controversy over effects of iNO on hemostasis in a clinical setting [31].…”

Section: Platelet Functionmentioning

confidence: 88%

“…In order to settle this issue we investigated the effects of 40 ppm NO inhalation prolonged to 30 h on bleeding time and coagulation parameters in healthy piglets. We consider it unlikely that clinical use of iNO would enhance the risk of bleeding even after prolonged inhalation [31]. Some platelet aggregation tests in different studies were performed using platelet rich plasma (PRP) in which the Hb is removed before the analysis.…”

Section: Platelet Functionmentioning

confidence: 99%

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ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – experimental and clinical evidence

Goździk¹,

Goździk²

2012

kitp

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New evidence indicates that nitric oxide inhalation leads to formation of new compounds which may be carried as thiol groups attached to protein in blood or act indirectly through nitrite and nitrate, metabolites which have been shown to elevate over time during exposure to inhaled NO. Additionally it has been shown that inhaled nitric oxide has no hemodynamic effects on normally perfused tissue, but increases blood flow selectively in ischemic tissue. It has a simple route of administration, safety profile and immediate action. Because of these properties, inhaled nitric oxide may serve as a rescue therapy for ischemic conditions in which collateral blood flow is important or until interventional or spontaneous reperfusion occurs. This review focuses on inhaled nitric oxide effects outside the lungs, and discusses its experimental and clinical applications, with particular attention to potential systemic effects of the gas. Key words: nitric oxide, ischemia, reperfusion injury, vasodilatation. StreszczenieDoniesienia ostatnich lat wskazują, że wziewne stosowanie tlenku azotu prowadzi do powstawania szeregu aktywnych związków chemicznych, głównie z grupy S-nitrozotioli, oraz nitrozylacji grup sulfhydrylowych różnych białek. Aktywność tlenku azotu może być również uzyskiwana pośrednio poprzez azotyny i azotany, produkty jego metabolizmu. Wszystkie te związki mogą przenosić aktywność biologiczną tlenku azotu do krążenia systemowego i działać jako bardziej stabilne źró-dło jego magazynowania. Dodatkowo wykazano, że wziewny tlenek azotu selektywnie zwiększa przepływ krwi w tkankach niedokrwionych, jednocześnie nie wykazując działań hemodynamicznych w tkankach perfundowanych prawidłowo. Wydaje się, że leczenie wziewnym tlenkiem azotu, ze względu na prosty sposób podaży oraz natychmiastowe działanie, może być przydatne jako terapia ratunkowa w różnych stanach niedokrwienia, w których istotna jest poprawa przepływu naczyniowego do czasu wystąpienia naturalnej lub interwencyjnej reperfuzji. W pracy przedstawiono szereg badań eksperymentalnych i klinicznych wskazujących na efekty działań systemowych wziewnego tlenku azotu, znacznie wykraczających poza łożysko płucne. Słowa kluczowe: tlenek azotu, niedokrwienie, reperfuzja, wazodylatacja.

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Section: Platelet Functionmentioning

confidence: 88%

Section: Platelet Functionmentioning

confidence: 99%

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – experimental and clinical evidence

Goździk¹,

Goździk²

2012

kitp

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“…Based on our previous experience with prolonged experimental studies in a porcine model [8], [19], this protocol involved 30 hours of endotoxin exposure using high-dose E. coli lipopolysaccharide (LPS) infusion, which resulted in multiple organ dysfunction after 12–24 hours. This study was intended to mimic the clinical setting, with an initial endotoxin insult and then resuscitative interventions initiated in real time over a prolonged study period.…”

Section: Discussionmentioning

confidence: 99%

“…We studied 30 domestic piglets, 2 months old, and with a median body weight of 21 kg (range 15–24 kg). We have previously described this model in detail [8], [19]. The piglets were fasted overnight prior to the study.…”

Section: Methodsmentioning

confidence: 99%

Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

Göranson

Goździk²,

Harbut

et al. 2014

PLoS ONE

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ObjectiveIt has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables.DesignRandomized controlled trial.SettingUniversity animal laboratory.SubjectsDomestic piglets (n = 30).InterventionsAnimals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid.Measurements and Main ResultsExposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups.ConclusionsThis study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion.

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“…New evidence indicates that NO inhalation leads to formation of new compounds which may be carried as thiol groups attached to protein in blood [10]. Another possibility is that inhaled NO acts indirectly through nitrite and nitrate, metabolites which have been shown to elevate over time during exposure to inhaled NO [11]. A growing body of evidence indicates that iNO has no hemodynamic effects on normally perfused tissue, but increases blood flow selectively in ischemic tissue [12].…”

Section: Introductionmentioning

confidence: 99%

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – proven and possible mechanisms

Goździk¹,

Goździk²

2012

kitp

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Inhaled nitric oxide has been shown to reduce pulmonary hypertension in several disease states. The vasodilatory effect of inhaled nitric oxide is limited almost exclusively to the pulmonary circulation, due to its rapid diffusion across the capillary membrane and its immediate deactivation by hemoglobin in the pulmonary vasculature lumen. However, many reports on the use of inhaled nitric oxide have revealed a broad spectrum of changes outside the lung. The remote effects are typically dose dependent and the mechanisms responsible for these effects are incompletely understood. New evidence indicates that nitric oxide inhalation leads to formation of new compounds which may be carried as thiol groups attached to protein in blood or act indirectly through nitrite metabolites. This review presents the mechanisms of inhaled nitric oxide conversion to active compounds/metabolites and discusses their actions beyond pulmonary circulation with special emphasis on the potential for systemic effects. Key words: respiratory system agents, nitric oxide, nitrite, S-nitrosothiol, ischemia, reperfusion injury. StreszczenieTlenek azotu stosowany wziewnie wykorzystywany jest w leczeniu różnych stanów chorobowych przebiegających z nadciś nieniem płucnym. Jego działania wazodylatacyjne ograniczone są wyłącznie do krążenia płucnego, ze względu na szybką dyfuzję przez błony kapilar płucnych i natychmiastową dezaktywację przez hemoglobinę. W ostatnim czasie jednak, pojawiło się wiele obserwacji wskazujących na szerokie spektrum działania wziewnego tlenku azotu również poza łożyskiem płuc-nym. Te odlegle systemowe efekty jego działania są zazwyczaj zależne od dawki, natomiast odpowiedzialne mechanizmy pozostają nie w pełni wyjaśnione. Wiele obserwacji wskazuje, że wdychanie tlenku azotu prowadzi do powstawania aktywnych Snitrozotioli oraz nitrozylacji grup sulfhydrylowych różnych białek. Wszystko to w połączeniu z aktywnością produktów jego metabolizmu azotynów i azotanów, może stanowić potencjalnie bardziej stabilne źródło magazynowania tlenku azotu w ustroju. Prezentowana praca przedstawia mechanizmy konwersji tlenku azotu do aktywnych metabolitów i omawia ich działania poza łożyskiem płucnym, ze szczególnym uwzględ-nieniem potencjału działań ogólnoustrojowych w warunkach upośledzonej perfuzji narządowej. Słowa kluczowe: tlenek azotu, uraz reperfuzyjny, azotyny, Sni trozotiole.

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Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets

Abstract: Prolonged exposure to iNO at 40[Symbol: see text]ppm did not affect bleeding time or coagulation parameters in healthy piglets. The findings do not support the hypothesis that iNO increases the risk of bleeding in humans.

Cited by 17 publications

References 37 publications

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – experimental and clinical evidence

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – experimental and clinical evidence

Organ Dysfunction among Piglets Treated with Inhaled Nitric Oxide and Intravenous Hydrocortisone during Prolonged Endotoxin Infusion

ANESTEZJOLOGIA I INTENSYWNA TERAPIA Inhaled nitric oxide effects outside the lungs – proven and possible mechanisms

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