Inhaled Nitric Oxide Selectively Reverses Human Hypoxic Pulmonary Vasoconstriction without Causing Systemic Vasodilation

Frostell, Claes; Blomqvist, Hans; Hedenstierna, Göran; Lundberg, Johan; Zapol, Warren M.

doi:10.1097/00000542-199303000-00005

Cited by 418 publications

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“…The initial impetus for the study was the inverse relation between pulmonary NO and pulmonary arterial pressure found in animal and human experiments (6,7,9,14,15,22,23,27,28). That relation was not found in this study, despite adequate statistical power.…”

Section: Discussionmentioning

confidence: 60%

“…An animal study using NO synthase gene transfer to the airway demonstrates elegantly that increasing NO decreases hypoxic pulmonary vasoconstriction (7). Studies of humans are consistent and have demonstrated that 1) NO is critical in regulating basal pulmonary vascular tone (10,27), 2) inhibiting NO synthesis exacerbates hypoxic pulmonary vasoconstriction, and 3) inhaling gas mixtures with high concentrations of NO diminishes hypoxic pulmonary vasoconstriction at sea level (6,15) and lowers pulmonary artery systolic pressure at high altitude (23). Moreover, sea-level natives exposed to acute hypoxia (and who have relatively high levels of exhaled NO) have less hypoxic pulmonary vasoconstriction, as measured by pulmonary artery systolic pressure (8,11).…”

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confidence: 97%

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Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

Hoit

Dalton

Erzurum³

et al. 2005

Journal of Applied Physiology

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When O 2 availability is reduced unavoidably, as it is at high altitude, a potential mechanism to improve O 2 delivery to tissues is an increase in blood flow. Nitric oxide (NO) regulates blood vessel diameter and can influence blood flow. This field study of intrapopulation variation at high altitude tested the hypothesis that the level of exhaled NO (a summary measure of pulmonary synthesis, consumption, and transfer from cells in the airway) is directly proportional to pulmonary, and thus systemic, blood flow. Twenty Tibetan male and 37 female healthy, nonsmoking, native residents at 4,200 m (13,900 ft), with an average O 2 saturation of hemoglobin of 85%, participated in the study. The geometric mean partial pressure of NO exhaled at a flow of 17 ml/s was 23.4 nmHg, significantly lower than that of a sea-level reference group. However, the rate of NO transfer out of the airway wall was seven times higher than at sea level, which implied the potential for vasodilation of the pulmonary blood vessels. Mean pulmonary blood flow (measured by cardiac index) was 2.7 Ϯ 0.1 (SE) l/min, and mean pulmonary artery systolic pressure was 31.4 Ϯ 0.9 (SE) mmHg. Higher exhaled NO was associated with higher pulmonary blood flow; yet there was no associated increase in pulmonary artery systolic pressure. The results suggest that NO in the lung may play a key beneficial role in allowing Tibetans at 4,200 m to compensate for ambient hypoxia with higher pulmonary blood flow and O 2 delivery without the consequences of higher pulmonary arterial pressure. high altitude; oxygen delivery; oxygen availability; hypoxia WHEN OXYGEN AVAILABILITY is reduced, as it is at high altitude, an increased blood flow could potentially improve O 2 delivery to tissues. However, the pulmonary vasoconstriction response to hypoxia decreases blood flow in the lung, the first point of contact with the circulation. This response probably evolved at sea level to maintain gas exchange by redistribution of blood flow from temporarily small, poorly oxygenated to betteroxygenated areas of the lung (17, 32). At high altitude, the entire lung is always hypoxic, and the resulting general vasoconstriction does not redistribute blood flow; instead, it increases pulmonary arterial pressure, sometimes causing pathological remodeling of the heart and lungs (30). However, many people live at high altitude without pulmonary hypertension or cardiac hypertrophy, which suggests that another factor may intervene to maintain blood flow when the blood carries less O 2 and the usual vasoconstriction response increases pulmonary resistance. That factor may be nitric oxide (NO), a vasodilator found in high concentrations in the lungs of high-altitude natives, particularly among Tibetans (5).A wealth of studies support a key role for NO in determining basal pulmonary vascular tone at sea level and in effecting the hypoxic vasoconstriction response. An animal study using NO synthase gene transfer to the airway demonstrates elegantly that increasing NO decreases hypoxic pulmonary v...

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Section: Discussionmentioning

confidence: 60%

mentioning

confidence: 97%

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

Hoit

Dalton

Erzurum³

et al. 2005

Journal of Applied Physiology

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“…5 For a decade, inhaled nitric oxide (iNO) has been used as a specific pulmonary vascular bed vasodilator, 5 thus improving right ventricular function by decreasing pulmonary hypertension. 6 Recently iNO has been used in pregnant patients with Eisenmenger's syndrome resulting in reduced hypoxemia and pulmonary artery pressure (PAP) although the patients died. 7,8 In this article we report the management and hemodynamic profile of a pregnant patient with PPH in whom we used iNO to control PAP during CS and in the postpartum period.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, an increase in preload, as seen during pregnancy (increase in blood volume and cardiac output) can easily result in right ventricular failure. [3][4][5][6][7][8] PPH indirectly alters left ventricular function due to a decrease in left ventricular preload and ventricular interdependence (via septal wall motion of the overloaded right ventricle). 9 Decrease in pulmonary hypertension lowers right ventricular afterload, improves right ventricular ejection fraction, decreases right ventricular work and size and improves both diastolic and systolic left ventricular function.…”

Section: Discussionmentioning

confidence: 99%

“…9 Decrease in pulmonary hypertension lowers right ventricular afterload, improves right ventricular ejection fraction, decreases right ventricular work and size and improves both diastolic and systolic left ventricular function. [6][7][8][9] The response of pulmonary arteries to vasodilation is important in the outcome of PPH in pregnant women. 3 iNO is a potent selective pulmonary vasodilator.…”

Section: Discussionmentioning

confidence: 99%

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Use of inhaled nitric oxide for emergency Cesarean section in a woman with unexpected primary pulmonary hypertension

Decoene¹,

Bourzoufi²,

Moreau³

et al. 2001

Can J Anesth/J Can Anesth

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The Pulmonary Effect of Nitric Oxide Synthase Inhibition Following Endotoxemia in a Swine Model

et al. 1994

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FObjective: To evaluate the pulmonary effect of treatMain Outcome Measures: Cardiopulmonary variment with N-nitro-L-arginine methyl ester (NAME) with ables and blood gases were measured serially. The muland without inhaled nitric oxide (NO) in a swine model tiple inert gas elimination technique was performed at 3 of endotoxemia.hours. The wet-to-dry lung weight ratio was measured following necropsy. Design: Randomized controlled trial.Results: Administration of LPS resulted in pulmonary Setting: Laboratory.arterial hypertension, pulmonary edema, and hypoxemia with increased ventilation perfusion ratio misInterventions: Following a 20-minute intravenous inmatching. None of these changes were attenuated by fusion of Escherichia coli lipopolysaccharide (LPS) (200 NAME treatment alone but all were significantly pLg/kg), animals were resuscitated with saline solution improved by the simultaneous administration of (1 mL/kg per minute) and observed for 3 hours while meinhaled NO. chanically ventilated (fraction of inspired oxygen [Fio,], 0.6; tidal volume, 12 mLikg; positive end-expiratory presConclusions: Systemic NO synthase inhibition failed to sure, 5 cm HRO). Group 1 (LPS, n=6) received no addirestore hypoxic pulmonary vasoconstriction following LPS tional treatment; group 2 (NAME, n=5) received NAME administration. The deleterious effects of endotoxemia (3 mg/kg per hour) for the last 2 hours; group 3 (NO, on pulmonary function can be improved by inhaled NO n=6) received NAME (3 mg/kg per hour) and inhaled NO but not by systemic inhibition of NO synthase. (40 ppm) for the last 2 hours; and group 4 (control, n=5) received only saline solution without LPS.(Arch Surg. 1994;129:1233-1239 S EPSIS RESULTS in a systemic in-lowing sepsis is a significant comorbid facflammatory response that is tor, therapy aimed at attenuating this mediated by various cytodeleterious process may exert a benefikines and activated leukocial effect on outcome. cytes. Systemic vasodilation Hypoxic pulmonary vasoconstricand hypotension characteristic of sepsis tion is a mechanism that modulates pulhave been hypothesized to occur secondmonary gas exchange by matching the disarily to endogenous overproduction of nitribution of blood flow to ventilation. 7 ,8 tric oxide (NO).',' In contrast to the sysHowever, the cellular mechanisms that initemic vasodilatory response, pulmonary tiate and maintain HPV remain poorly un-

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Inhaled Nitric Oxide Selectively Reverses Human Hypoxic Pulmonary Vasoconstriction without Causing Systemic Vasodilation

Cited by 418 publications

References 0 publications

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

Nitric oxide and cardiopulmonary hemodynamics in Tibetan highlanders

Use of inhaled nitric oxide for emergency Cesarean section in a woman with unexpected primary pulmonary hypertension

The Pulmonary Effect of Nitric Oxide Synthase Inhibition Following Endotoxemia in a Swine Model

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