Inhaled nitric oxide improves systemic microcirculation in infants with hypoxemic respiratory failure

Top, Anke P. C.; İnce, Can; Schouwenberg, Patrick H. M.; Tibboel, Dick

doi:10.1097/pcc.0b013e31820ac0b3

Cited by 30 publications

(27 citation statements)

References 31 publications

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“…In subsequent studies, the family of circulating S-nitrosylated proteins (SNO-proteins) was expanded to include S-nitrosohemoglobin (SNO-Hb), 10 which exhibits the remarkable ability to mediate hypoxic vasodilation, 11 the selective vasodilation in proportion to degree of hypoxemia. A number of recent studies have provided evidence that iNO may utilize SNO-based pathways 12 to confer protection against ischemic insults 8,[13][14][15][16][17][18] -none more remarkable than the report by Terpolilli et al 19 in this issue of Circulation Research, which illustrates beautifully in cerebral vessels the principles of endocrine NO bioactivity and hypoxia-coupled delivery of NO bioactivity. Their demonstration that iNO promotes dilation of cerebral resistance vessels selectively in hypoperfused tissue, without changes in systemic blood pressure, points to new strategies to ameliorate damage after ischemic insult.…”

mentioning

confidence: 68%

Endocrine Nitric Oxide Bioactivity and Hypoxic Vasodilation by Inhaled Nitric Oxide

Stamler¹,

Reynolds²,

Hess

2012

Circulation Research

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Inhaled nitric oxide (iNO) is approved by the Food and Drug Administration for the treatment of persistent pulmonary hypertension of the newborn, largely as a result of the pioneering research efforts of Warren Zapol. Inhaled nitric oxide (NO) dilates pulmonary resistance vessels to improve ventilation-perfusion matching before being inactivated by reactions with hemoglobin (Hb) in blood exiting the lung. Inhaled NO therefore is a selective pulmonary vasodilator. 1 Notwithstanding the validity of this model, investigators including Claes Frostell 2 and David Wessel 3 noted early on that high therapeutic doses of iNO led to subtle decreases in blood pressure. It had recently been discovered that albumin could be S-nitrosylated by NO, 4 endowing it with long-lived vasodilatory activity. So, when presented with the quandary of systemic effects, it was quickly demonstrated that iNO could S-nitrosylate plasma proteins, 5 potentially providing systemic vasodilatory activity 6 and thus acting in an endocrine-like manner. S-nitrosoalbumin since has been implicated in protection by iNO against reperfusion injury in systemic vessels, 7,8 but also may form within airways of iNO-treated patients, 5,9 potentially contributing to "pulmonary selectivity." In subsequent studies, the family of circulating S-nitrosylated proteins (SNO-proteins) was expanded to include S-nitrosohemoglobin (SNO-Hb), 10 which exhibits the remarkable ability to mediate hypoxic vasodilation, 11 the selective vasodilation in proportion to degree of hypoxemia. A number of recent studies have provided evidence that iNO may utilize SNO-based pathways 12 to confer protection against ischemic insults 8,13-18 -none more remarkable than the report by Terpolilli et al 19 in this issue of Circulation Research, which illustrates beautifully in cerebral vessels the principles of endocrine NO bioactivity and hypoxia-coupled delivery of NO bioactivity. Their demonstration that iNO promotes dilation of cerebral resistance vessels selectively in hypoperfused tissue, without changes in systemic blood pressure, points to new strategies to ameliorate damage after ischemic insult. Article, see p 727Notable findings in this study include: (1) iNO increased circulating levels of SNO-Hb and the SNO-Hb-generating substrate, nitrite; (2) iNO selectively dilated pial venules under normoxic conditions and dilated both venules and arterioles under conditions of hypoperfusion and ischemic insult; and (3) neuroprotection by iNO was correlated with the delivery of NO to ischemic cerebral vessels and resultant vasodilation. It is known that SNO-Hb can actuate graded vasodilation in the brain across a wide range of oxygen tensions. 20 Thus, Terpolilli et al 19 not only demonstrate that iNO increases the levels of a naturally occurring vasodilator that functions to transduce O 2 concentrations, but also actually record directly the in situ delivery of NO-based activity that subserves hypoxic vasodilation.The finding that inhalation of NO leads to increases in SNO-Hb is consistent with...

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mentioning

confidence: 68%

Endocrine Nitric Oxide Bioactivity and Hypoxic Vasodilation by Inhaled Nitric Oxide

Stamler¹,

Reynolds²,

Hess

2012

Circulation Research

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“…Therefore, measuring microcirculatory blood flow could be regarded as an important addition to the usual macrocirculatory parameters. Microcirculatory parameters have been shown to be able to visualize dysfunctional microcirculation in septic shock in children, effects of inhaled nitric oxide in children with hypoxemic respiratory failure, and in children receiving extracorporeal membrane oxygenation (29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Microcirculatory mechanisms in postnatal hypotension affecting premature infants

et al. 2013

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“…(45) In the only human infant study, patients treated for respiratory failure with inhaled nitric oxide had increased buccal blood flow, confirming its action on peripheral microvasculature. (46) To date, there have been 2 randomized clinical trials in adults of inhaled nitric oxide for the treatment of existing microcirculatory disease. (47) (48) In both adult studies, no difference between the treatment and control arms was reported.…”

Section: Can the Effect Of Hypoxic Vasodilation Be Augmented?mentioning

confidence: 99%

Red Blood Cell Storage in Transfusion-Related Acute Gut Injury

et al. 2015

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and The iNO-TRAGI Trial. This commentary does contain a discussion of an unapproved/ investigative use of a commercial product/ device. Educational Gaps1. Transfusion-associated gut injury is the occurrence of necrotizing enterocolitis 48 hours or less after packed red blood cell transfusion given for anemia in low-risk infants born at extremely low gestational age. 2. Blood storage alters the red blood cells, creating a storage lesion that may affect infants born at extremely low gestational ages who are at the cusp of an oxygen delivery-consumption imbalance. AbstractTransfusion-related acute gut injury is defined as the occurrence of necrotizing enterocolitis 48 hours or less after a packed red blood cell (PRBC) transfusion for marked anemia in older, low-risk infants born at extremely low gestational ages (<28 weeks' gestational age) who are no longer experiencing any historically associated risk factors except enteral feeding. As oxygen delivery decreases with advancing anemia, growing premature neonates compensate by redistribution of blood flow, increased cardiac output, and elevated oxygen extraction. Further adjustments to microvascular blood flow arise from nitric oxide-based hypoxic vasodilation, which eventually becomes limiting for sustaining oxygen consumption. Among many effects on red blood cells (RBC), storage lowers donor RBC nitric oxide content and increases free hemoglobin nitric oxide scavenging, whereas low oxygenation reduces nitric oxide production by endothelial nitric oxide synthase; these varied mechanisms collectively result in mitigation of hypoxic vasodilation. Because the adverse effect of packed RBCs on neonatal gut oxygenation appears primarily in association with extreme anemia, a sudden reduction in mucosal blood flow during periods of increased oxygen demand (enteral feeding) presumably results in injury to the physical barrier, enabling bacterial invasion and necrotizing enterocolitis. In infants born at extremely low gestational ages, PRBC transfusions for iatrogenic or developmentally acquired anemia are common and will persist even after all conservation techniques, microassay methods, and use of erythropoietin have been implemented. A fixed need for transfusions exists because of additional biologic restrictions imposed by normal rates of human somatic growth coupled with limits of RBC production to accommodate the need for an expanding RBC mass. Improved understanding of etiologic mechanisms of microvascular injury with transfusion should be instructive to clinicians in managing this dilemma.Objectives After completing this article, readers should be able to:1. Define and identify the risk factors associated with transfusion-related acute gut injury (TRAGI). 2. Outline the mechanisms by which blood transfusions might be implicated in the occurrence of TRAGI. 3. Explain the concept of hypoxic vasodilation and its value in the maintenance of microvascular circulation under hypoxic conditions. 4. Discuss potential strategies to decrease the risk of TRAGI in infants born at ...

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Inhaled nitric oxide improves systemic microcirculation in infants with hypoxemic respiratory failure

Abstract: Inhaled nitric oxide improves the systemic microcirculation in children with hypoxemic respiratory failure.

Cited by 30 publications

References 31 publications

Endocrine Nitric Oxide Bioactivity and Hypoxic Vasodilation by Inhaled Nitric Oxide

Endocrine Nitric Oxide Bioactivity and Hypoxic Vasodilation by Inhaled Nitric Oxide

Microcirculatory mechanisms in postnatal hypotension affecting premature infants

Red Blood Cell Storage in Transfusion-Related Acute Gut Injury

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