Inhaled nitric oxide inhibits the release of matrix metalloproteinase-2, but not platelet activation, during extracorporeal membrane oxygenation in adult rabbits

Cheung, Po-Yin; Sawicki, Grzegorz; Peliowski, Abraham; Etches, Philip C.; Schulz, Richard; Radomski, Marek W.

doi:10.1053/jpsu.2003.50116

Cited by 7 publications

(9 citation statements)

References 19 publications

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“…We previously reported that the plasma MMP-9 activity was not different, whereas the plasma MMP-2 activity increased gradually over the first day of extracorporeal membrane oxygenation in critically ill newborns (26). Interestingly, the activity of both plasma MMP-2 and -9 was increased in adult rabbits that underwent extracorporeal membrane oxygenation (11). Oxidative stress can contribute to the activation of MMPs (10,12).…”

Section: Discussionmentioning

confidence: 94%

“…TxB 2 is a stable metabolite of thromboxane A 2 , which is a marker of platelet activation, and the plasma levels of this eicosanoid were assayed using a commercially available immunoassay kit (R&D Systems Inc., Minneapolis, MN). MMP-2 and -9 activity in plasma was studied by gelatin zymography, as described previously (11). Briefly, samples were mixed with sodium dodecylsulfate sample buffer and subjected to 8% polyacrylamide separating gels containing gelatin (2 mg/mL, Sigma Chemical Co.).…”

Section: Methodsmentioning

confidence: 99%

“…MMPs are activated by proteolysis and oxidants including the peroxynitrite anion (6,10). Increased plasma MMP-2 and -9 activity with platelet dysfunction was observed in an animal model of extracorporeal circulation with a high oxygen environment (11). Lemke et al (12) recently reported a surge in plasma MMP-9 activity in the first day of postnatal life, which is consistent with a change from a low to a high oxygen environment.…”

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confidence: 88%

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Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

et al. 2006

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Hemostatic disturbances are common in asphyxiated newborns after resuscitation. We compared platelet function in hypoxic newborn piglets reoxygenated with 21% or 100% oxygen. Piglets (1-3 d, 1.5-2.1 kg) were anesthetized and acutely instrumented for hemodynamic monitoring. After stabilization, normocapnic hypoxia was induced with an inspired oxygen concentration of 10 -15% for 2 h. Piglets were then resuscitated for 1 h with 21% or 100% oxygen, followed by 3 h with 21% oxygen. Platelet counts and collagen (2, 5, and 10 g/mL)-stimulated whole blood aggregation were studied before hypoxia and at 4 h of post-hypoxia/ reoxygenation. Platelet function was studied using transmission electron microscopy and by measuring plasma thromboxane B 2 (TxB 2 ) and matrix metalloproteinase (MMP)-2 and -9 levels. Control piglets were sham-operated without hypoxia/reoxygenation. The hypoxemic (PaO 2 33 mm Hg) piglets developed hypotension with metabolic acidosis (pH 7.02-7.05). Upon reoxygenation, piglets recovered and blood gases gradually normalized. At 4 h reoxygenation, platelet aggregation ex vivo was impaired as evidenced by a rightwarddownward shifting of the concentration-response curves. Electron microscopy showed features of platelet activation. Plasma MMP-9 but not MMP-2 activity significantly increased. Resuscitation with 100% but not 21% oxygen increased plasma TxB 2 levels. Platelet counts decreased after hypoxia/reoxygenation but were not different between groups during the experiment. Resuscitation of hypoxic newborn piglets caused platelet activation with significant deterioration of platelet aggregation ex vivo and increased plasma MMP-9 levels. High oxygen concentrations may aggravate the activation of prostaglandin-thromboxane mechanistic pathway. MMP-2 (constitutive isoform, 72 kD) and MMP-9 (inducible isoform, 92 kD) are zinc-dependent endopeptidases that play an important role in the regulation of platelet aggregation (6 -9). MMPs are activated by proteolysis and oxidants including the peroxynitrite anion (6,10). Increased plasma MMP-2 and -9 activity with platelet dysfunction was observed in an animal model of extracorporeal circulation with a high oxygen environment (11). Lemke et al. (12) recently reported a surge in plasma MMP-9 activity in the first day of postnatal life, which is consistent with a change from a low to a high oxygen environment. Interestingly, in neonatal models of asphyxia, resuscitation with 100% oxygen is associated with higher oxidative stress and MMP-2 activities in the heart and brain than those with 21% oxygen (13,14). However, there is little information on the activity of MMPs in plasma and its relationship to platelet aggregatory function in the reoxygenation of asphyxiated newborns.Asphyxiated infants are often resuscitated with 100% oxygen, and this is associated with increased oxidative stress up to 28 d after birth (15). In the midst of the debate between the use of 21% or 100% oxygen in the resuscitation of asphyxiated newborns, we designed this study to examin...

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Section: Discussionmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 88%

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Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

et al. 2006

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“…Consequently, application of NO by inhalation for a short period before onset of ischemia has been demonstrated to prevent the detrimental effects of an I/R cycle on lung function [22]. Several lines of evidence have shown that NO suppresses expression or secretion and activation of MMPs, at least of gelatinases, in lung tissue or in isolated lung epithelial cells [23][24][25][26], but contradictory results have also been reported [27]. In the present communication, the hypothesis is tested that NO inhalation in the preconditioning mode suppresses I/Rinduced effects on MMPs and NE.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Ischemia/Reperfusion-Induced Accumulation of Matrix Metalloproteinases in Rat Lung by Preconditioning With Nitric Oxide

Waldow¹,

Witt²,

Бузин³

et al. 2009

Journal of Surgical Research

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“…Deficyt ten dotyczy parametrów ilościowych i jakościowych, objawiając się znacznym upo śledzeniem funkcji płytek pomimo prawidłowych wartości w badaniu morfologii krwi. Przeprowadzone dotychczas nieliczne badania wpływu tlenku azotu podawanego bez pośrednio do układu pozaustrojowego natleniania krwi su gerują protekcyjny wpływ tego czynnika na funkcję płytek krwi [4][5][6]. …”

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Evaluation of the effect of nitric oxide on platelets during cardiopulmonary bypass

Pawlak¹,

Śliwka²,

Żegleń³

et al. 2012

kitp

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WstępOperacje kardiochirurgiczne przeprowadzane z zasto sowaniem techniki krążenia pozaustrojowego są bardzo rozległymi procedurami medycznymi powiązanymi z rela tywnie dużą utratą krwi zarówno w trakcie zabiegu, jak i w okresie pooperacyjnym. Procedury medyczne prowa dzące do ograniczenia ilości przetaczanych preparatów krwi mają istotny wpływ na przebieg leczenia pooperacyj nego, a przede wszystkim na szacunkowy czas życia po operacji [1]. W wielu badaniach klinicznych zauważa się wyraźną korelację pomiędzy czasem przeżycia po zabie gach kardiochirurgicznych i ilością utraconej krwi. Jednym z istotniejszych elementów decydujących o utracie krwi w przebiegu operacji kardiochirurgicznych jest uszkodzenie płytek krwi na sztucznych powierzchniach systemów krąże nia pozaustrojowego [2,3]. Deficyt ten dotyczy parametrów ilościowych i jakościowych, objawiając się znacznym upo śledzeniem funkcji płytek pomimo prawidłowych wartości w badaniu morfologii krwi. Przeprowadzone dotychczas nieliczne badania wpływu tlenku azotu podawanego bez pośrednio do układu pozaustrojowego natleniania krwi su gerują protekcyjny wpływ tego czynnika na funkcję płytek krwi [4][5][6]. Cel pracyCelem pracy jest określenie działania tlenku azotu po dawanego do układu natleniania pozaustrojowego w trak cie operacji na otwartym sercu -wymiany zastawki aor talnej. Operacje naprawcze wrodzonych i nabytych wad serca przeprowadzane są z zastosowaniem krążenia po KARDIOCHIRURGIA DOROSŁYCH Adres do korespondencji: dr n. med. Szymon Pawlak, Katedra i Oddział Kliniczny Kardiochirurgii i Transplantologii, Śląskie Centrum Chorób Serca, ul. M. CurieSkłodowskiej 9, 41800 Zabrze, tel./faks +48 32 373 36 37, email: pawlaks@poczta.fm StreszczeniePrzeprowadzone badanie miało na celu analizę ochronnego wpływu tlenku azotu na płytki krwi. Badaniem objęto 15 pa cjentów podzielonych losowo na dwie grupy. W grupie badanej podawano tlenek azotu do układu oksygenatora w stężeniu 10 ppm. Grupa kontrolna była poddana standardowej procedu rze. Wszystkim pacjentom pobierano krew w trzech punktach czasowych: przed zabiegiem chirurgicznym, bezpośrednio po zakończeniu zabiegu oraz po upływie co najmniej 24 godzin od operacji kardiochirurgicznej. Wykonano następujące bada nia: ASPItest, ADPtest, morfologia oraz oznaczenie agrega tów monocytarnopłytkowych -VASPP, CD41a, CD42a, CD61 -metodą cytometrii przepływowej. W przeprowadzonych do tychczas badaniach nie uwidoczniono istotnej statystycznie różnicy badanych parametrów pomiędzy grupami. Słowa kluczowe: tlenek azotu, krążenie pozaustrojowe. Ocena działania tlenku azotu na płytki krwi w trakcie krążenia pozaustrojowegoEvaluation of the effect of nitric oxide on platelets during cardiopulmonary bypass AbstractThe aim of the study was to evaluate the protective effects of nitric oxide on platelets. The study included fifteen patients divided into two random groups. In the test group nitric oxide was added to the oxygenator at a concentration of 10 ppm. The control group was subjected to the standard procedure. In all patients, ...

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Inhaled nitric oxide inhibits the release of matrix metalloproteinase-2, but not platelet activation, during extracorporeal membrane oxygenation in adult rabbits

Cited by 7 publications

References 19 publications

Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

Platelet Dysfunction in Asphyxiated Newborn Piglets Resuscitated with 21% and 100% Oxygen

Prevention of Ischemia/Reperfusion-Induced Accumulation of Matrix Metalloproteinases in Rat Lung by Preconditioning With Nitric Oxide

Evaluation of the effect of nitric oxide on platelets during cardiopulmonary bypass

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