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Titolo:
Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model
Autore:
Martinez-Ruiz, R; Montero-Huerta, P; Hromi, J; Head, CA;
Indirizzi:
Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 thesia & Crit Care, Boston, MA 02114 USA
Titolo Testata:
ANESTHESIOLOGY
fascicolo: 6, volume: 94, anno: 2001,
pagine: 1113 - 1118
SICI:
0003-3022(200106)94:6<1113:INOISR>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
OXYGEN-AFFINITY; PULMONARY VASOCONSTRICTION; S-NITROSOHEMOGLOBIN; BLOOD-FLOW; HEMOGLOBIN; DISEASE; VASOOCCLUSION; INHIBITION; GELATION; ANEMIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Head, CA Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA Harvard Univ Boston MA USA 02114 Crit Care, Boston, MA 02114 USA
Citazione:
R. Martinez-Ruiz et al., "Inhaled nitric oxide improves survival rates during hypoxia in a sickle cell (SAD) mouse model", ANESTHESIOL, 94(6), 2001, pp. 1113-1118

Abstract

Background: The hallmark of sickle cell disease (SCD) is erythrocyte sickling during deoxygenation of the abnormal hemoglobin S (HbS), When HbS is deoxygenated, it aggregates into polymers, resulting in distortion of the erythrocyte structure, producing microvascular thrombosis and ischemia, The transgenic SAD mouse produces three types of human hemoglobin: S, Antilles, and D-Punjab (HbSAD) and provides an animal model for SCD. We studied the effects of nitric oxide (NO) breathing at various doses and time regimens in the presence of severe hypoxia (6% oxygen) using the SAD mouse model, Methods: Age- and sex-matched control and SAD mice were exposed to 6% oxygen breathing in an environmental chamber and assessed for survival up to 1 h. Animals received different inhaled NO concentrations before and/or during hypoxia, Blood was obtained to evaluate the oxyhemoglobin dissociation curve and measure methemoglobinemia. Results: Pretreatment by breathing NO at 20 ppm by volume in air for 30 min, and continuing to breathe 20 ppm NO during hypoxia resulted in improvement in survival rates in the SAD mouse (75%, n =8) as compared with control SAD mice (11%, n = 9;P < 0.001), Pretreatment alone or breathing lower doses of NO were not protective, Changes in HbSAD oxygen affinity were not detected with NO breathing, and methemoglobin levels were low in ah surviving mice. Conclusions: Breathing NO produced a rapid, protective effect to severe hypoxic stress in SAD mice, There appears tobe a required loading period between NO breathing and its beneficial effect during hypoxic stress, possibly because of the total amount of NO delivered to SAD hemoglobin, blood cell components, and endothelium. NO breathing may be beneficial as a therapeutic intervention in SCD.

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Documento generato il 30/03/20 alle ore 19:32:05