Effects of Oxygen Breathing on Pulmonary Vascular Input Impedance in Patients with Pulmonary Hypertension

Haneda, Takashi; Nakajima, Toshiyuki; Shirato, Kunio; Onodera, S.; Takishima, Tamotsu

doi:10.1378/chest.83.3.520

Cited by 54 publications

(40 citation statements)

References 29 publications

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“…A study on pulmonary vascular impedance in patients with pulmonary hypertension of various etiologies reported a decrease in circulating norepinephrine after hyperoxic breathing. 3 In our patients hyperoxia on average corrected one fourth of abnormally increased MSNA, indicating that most of the increased sympathetic activity in PAH patients is not the consequence of mild hypoxemia-related chemoreflex activation. Interestingly, sympathetic and HR responses to hyperoxic breathing in our patients with PAH contrast with those of patients with congestive left ventricular failure, in whom we observed that hyperoxia did not improve sympathetic hyperactivity.…”

Section: Discussionsupporting

confidence: 52%

“…One study reported a nonsignificant increase in circulating catecholamines that correlated positively with pulmonary vascular resistance and circulating endothelin and negatively with survival. 6 The other studies reported circulating norepinephrine to be either increased 3,4 or normal. 5 These discrepancies might be explained by the fact that plasma catecholamines are affected by neuronal release, reuptake, spillover, and degradation and are therefore insensitive markers of sympathetic nerve outflow in pathological conditions.…”

Section: Discussionmentioning

confidence: 98%

“…A series of biological abnormalities have been described that involve all the compartments of the pulmonary arterial wall, 2 but little is known about a possible participation of the sympathetic nervous system. Circulating catecholamines in PAH have been reported either to be increased 3,4 or to remain within normal limits. 5,6 These discrepancies may be related to the fact that circulating catecholamines are imperfect markers of sympathetic nervous system activity, being affected by a variety of processes, including changes in synthesis, metabolism, and facilitation of release by the peripheral nerve endings.…”

mentioning

confidence: 99%

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Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Velez‐Roa¹,

Ciarka²,

Najem³

et al. 2004

Circulation

385

272

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Background-This study tested the hypothesis that sympathetic nerve activity is increased in pulmonary artery hypertension (PAH), a rare disease of poor prognosis and incompletely understood pathophysiology. We subsequently explored whether chemoreflex activation contributes to sympathoexcitation in PAH. Methods and Results-We measured muscle sympathetic nerve activity (MSNA) by microneurography, heart rate (HR), and arterial oxygen saturation (SaO 2 ) in 17 patients with PAH and 12 control subjects. The patients also underwent cardiac echography, right heart catheterization, and a 6-minute walk test with dyspnea scoring. Circulating catecholamines were determined in 8 of the patients. Chemoreflex deactivation by 100% O 2 was assessed in 14 patients with the use of a randomized, double-blind, placebo-controlled, crossover study design. Sympathetic hyperactivity in PAH is partially chemoreflex mediated and may be related to disease severity.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Velez‐Roa¹,

Ciarka²,

Najem³

et al. 2004

Circulation

385

272

View full text Add to dashboard Cite

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“…Hyperactivation of the sympathetic nervous system is reported in (Haneda et al, 1983;Salvi, 1999;Nagaya et al, 2000;Velez-Roa et al, 2004), and circulating levels of catecholamines are increased in the MCT model of PAH (Clozel et al, 2006). Vasorelaxation of EPA and IPA rings to ACT-333679 and treprostinil, in the presence and absence of endothelium, was therefore measured after contraction of rings with the ␣ 1 -adrenoceptor agonist phenylephrine.…”

Section: Resultsmentioning

confidence: 99%

Differential Effects of Selexipag and Prostacyclin Analogs in Rat Pulmonary Artery

Morrison

Studer

Ernst

et al. 2012

J Pharmacol Exp Ther

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{4-[(5,6-Diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}acetic acid (ACT-333679) is the main metabolite of the selective prostacyclin (PGI 2 ) receptor (IP receptor) agonist selexipag. The goal of this study was to determine the influence of IP receptor selectivity on the vasorelaxant efficacy of ACT-333679 and the PGI 2 analog treprostinil in pulmonary artery under conditions associated with pulmonary arterial hypertension (PAH). Selexipag and ACT-333679 evoked full relaxation of pulmonary artery from control and monocrotaline (MCT)-PAH rats, and ACT-333679 relaxed normal pulmonary artery contracted with either endothelin-1 (ET-1) or phenylephrine. In contrast, treprostinil evoked weaker relaxation than ACT-333679 of control pulmonary artery and failed to induce relaxation of pulmonary artery from MCT-PAH rats. Treprostinil did not evoke relaxation of normal pulmonary artery contracted with either ET-1 or phenylephrine. Expression of prostaglandin E 3 (EP 3 ) receptor mRNA was increased in pulmonary artery from MCT-PAH rats.In contraction experiments, the selective EP 3 receptor agonist sulprostone evoked significantly greater contraction of pulmonary artery from MCT-PAH rats compared with control rats. The presence of a threshold concentration of ET-1 significantly augmented the contractile response to sulprostone in normal pulmonary artery. ACT-333679 did not evoke direct contraction of rat pulmonary artery, whereas treprostinil evoked concentration-dependent contraction that was inhibited by the EP 3 receptor antagonist (2E)-3-(3Ј,4Ј-dichlorobiphenyl-2-yl)-N-(2-thienylsulfonyl)acrylamide. Antagonism of EP 3 receptors also revealed a relaxant response to treprostinil in normal pulmonary artery contracted with ET-1. These data demonstrate that the relaxant efficacy of the selective IP receptor agonist selexipag and its metabolite ACT-333679 is not modified under conditions associated with PAH, whereas relaxation to treprostinil may be limited in the presence of mediators of disease.

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“…To date, studies examining the sympathetic nervous system in patients with PAH have employed measures of systemic catecholamine concentrations, recordings of peripheral sympathetic nerve firing rate, as well as heart rate variability analysis. Some studies describe an increase in circulating catecholamine levels (24,31,36), but this has not been a consistent finding (39,44). These contradictory findings are not surprising; circulating NE plasma levels are an imperfect measure of sympathetic tone, since they are not only the result of NE release, but also uptake, metabolism, and clearance.…”

Section: Discussionmentioning

confidence: 99%

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

Mak

Witte

Al‐Hesayen

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Patients with congestive heart failure (CHF) due to left ventricular (LV) dysfunction have sympathetic activation specifically directed to the myocardium. Although pulmonary arterial hypertension (PAH) is associated with increased systemic sympathetic activity, its impact on sympathetic drive to ventricular myocardium is unknown. Fifteen patients with PAH (9 women; 54 Ϯ 12 years) were studied: 10 with idiopathic PAH and 5 with a connective tissue disorder. We measured hemodynamics, as well as radiolabeled and endogenous concentrations of arterial and coronary sinus norepinephrine (NE). These measures were repeated after inhaled nitric oxide (NO). Measurement of transcardiac NE concentrations and the cardiac extraction of radiolabeled NE allowed calculation of the corrected transcardiac gradient of NE (CTCG of NE). Comparative data were collected from 15 patients (9 women: 55 Ϯ 12 yr) with normal LV function and 15 patients with CHF (10 women; 53 Ϯ 12 yr). PAH patients had elevated arterial NE concentrations compared with those with normal LV function but were similar to those with CHF. The CTCG of NE was higher in those with PAH than in the normal LV group (3.6 Ϯ 2.2 vs. 1.5 Ϯ 0.9 pmol/ml; P Ͻ 0.01) but similar to that seen in those with CHF (3.3 Ϯ 1.4; P ϭ NS). Inhaled NO, which reduced pulmonary artery pressure and increased cardiac output, had no effect on cardiac sympathetic activity. Therefore, cardiac sympathetic activation occurs in PAH. The mechanism of this activation remains uncertain but does not involve elevations in left heart filling pressure. pulmonary hypertension; norepinephrine; hemodynamics PULMONARY HYPERTENSION IS defined as a mean pulmonary artery pressure of more than 25 mmHg at rest and is classified into five groups based upon etiology (42, 43). Idiopathic pulmonary arterial hypertension (IPAH) and other forms of pulmonary hypertension due to abnormalities in the pulmonary vasculature [pulmonary arterial hypertension (PAH)] require the exclusion of other causes, particularly abnormalities of left heart function.

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Effects of Oxygen Breathing on Pulmonary Vascular Input Impedance in Patients with Pulmonary Hypertension

Cited by 54 publications

References 29 publications

Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Increased Sympathetic Nerve Activity in Pulmonary Artery Hypertension

Differential Effects of Selexipag and Prostacyclin Analogs in Rat Pulmonary Artery

Cardiac sympathetic activation in patients with pulmonary arterial hypertension

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