Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin

Carteaux, Jean‐Pierre; Roux, Sébastiên; Siaghy, M.; Bruno, Schjoth; Dolofon, Patricia; Bechamps, Yves; Mertès, Paul-Michel; Villemot, Jean‐Pierre

doi:10.1016/s1010-7940(99)00017-2

Cited by 23 publications

(21 citation statements)

References 15 publications

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“…233 No clinical reports exist of bosentan used for this indication; however, a preclinical study demonstrated its ability to prevent PH associated with cardiopulmonary bypass. 234 are all mandatory elements of the assessment of these patients. …”

Section: Postoperative Pulmonary Hypertensionmentioning

confidence: 99%

ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

McLaughlin¹,

Archer²,

Badesch³

et al. 2009

Circulation

1,077

605

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Section: Postoperative Pulmonary Hypertensionmentioning

confidence: 99%

ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

McLaughlin¹,

Archer²,

Badesch³

et al. 2009

Circulation

1,077

605

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“…In addition, the augmented pulmonary vascular reactivity following CPB, which is responsible for the potential life-threatening acute increases in PVR, was also completely blocked in those lambs pretreated with endothelin receptor antagonists (43,44). Similarly, in normal pigs and piglets, blockade with bosentan not only attenuated the increase in PVR following CPB, but also improved pulmonary function and decreased leukocyte-mediated lung injury (35,36). Lastly, in children with congenital heart disease, a 20 min infusion of BQ 123, an ETA-selective antagonist, decreased pulmonary vascular resistance following surgical repair with the use of CPB (47).…”

Section: Et-1 After Cardiac Surgery For Congenital Heart Diseasementioning

confidence: 97%

“…In particular, ET-1 levels are significantly increased in humans and animals during a variety of models of ischemia-reperfusion injury, including hypothermic CPB (35)(36)(37)(38)(39). In ischemia reperfusion, it has been shown that ET-1 becomes dominant whereas the production of NO becomes impaired and this imbalance contributes to ischemia reperfusion injury.…”

Section: Et-1 After Cardiac Surgery For Congenital Heart Diseasementioning

confidence: 99%

“…During CPB, several factors including the disruption of normal pulmonary blood flow (36,37), complement activation, neutrophil activation, surgical stress, hypothermia, and alveolar hypoxia, induce further pulmonary vascular endothelial dysfunction and ET-1 production (37). In several animal and human studies, plasma ET-1 concentrations are consistently increased during and following CPB (36,43,44). In piglets, this was associated with increased endothelin gene expression and receptors.…”

Section: Et-1 After Cardiac Surgery For Congenital Heart Diseasementioning

confidence: 99%

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Endothelin-1 in Congenital Heart Disease

Beghetti¹,

Black

Fineman

2005

Pediatr Res

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Endothelin-1 (ET-1) is a 21-amino acid polypeptide produced primarily by vascular endothelial cells. First discovered in 1988 as a potent vasoconstrictor, it has subsequently been appreciated to participate in several biologic activities, including vascular smooth muscle proliferation, fibrosis, cardiac and vascular hypertrophy, and inflammation. Increasing data demonstrate alterations in ET-1 signaling in newborns, infants, and children with congenital heart defects that are associated with alterations in pulmonary blood flow. This review outlines the pathophysiologic role of the ET-1 cascade in the development of altered pulmonary vascular tone and reactivity that occurs with congenital heart disease and its repair, following the use of cardiopulmonary bypass. In addition, therapeutic implications for the use of novel ET receptor antagonists will be emphasized. Abbreviations CPB, cardiopulmonary bypass CHD, congenital heart defect ET-1, endothelin 1, PVR, pulmonary vascular resistance ET-1 was originally isolated in 1988 as a 21-amino acid polypeptide produced by pulmonary and systemic vascular endothelial cells, and was described as the most potent endogenous vasoconstrictor discovered to date (1). Subsequently it has been appreciated that ET-1 may be produced by a variety of cell types, and has numerous biologic properties within the cardiovascular, respiratory, renal, endocrine, gastrointestinal, and neurologic systems. These biologic properties include the regulation of vasomotor tone, vascular smooth muscle proliferation, fibrosis, cardiac and vascular hypertrophy, and inflammation (Fig. 1). In addition, alterations in the ET-1 cascade have been implicated in the pathophysiology of a variety of disease states, including congestive heart failure, bronchoconstriction, fibrotic disorders, and pulmonary hypertension (2-5). Increasing data demonstrate alterations in ET-1 signaling in newborns, infants, and children with congenital heart defects (CHD) that are associated with alterations in pulmonary blood flow (6 -10). This review outlines the pathophysiologic role of the ET-1 cascade in the development of altered pulmonary vascular tone and reactivity that occurs with congenital heart disease and its repair, following the use of cardiopulmonary bypass (CPB). In addition, therapeutic implications for the use of novel ET receptor antagonists will be emphasized. THE ENDOTHELIN CASCADEThe gene for human ET-1 is located on chromosome 6 and is translated to a 203-amino acid peptide precursor (preproET-1), which is then cleaved to form proendothelin-1. Proendothelin, big ET-1, is then cleaved by a membrane-bound metalloprotein converting enzyme (Endothelin Converting Enzyme-1, ECE-1) into its functional form (2,3,5,11). The biologic effects of ET-1 are mediated by at least two distinctive receptor populations, ET A and ET B , the densities of which are different depending on age, species, pathologic state, and vascular bed studied. The ET A receptors are located on vascular smooth muscle cells and mediate vasoconstr...

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“…These models mimic some of the clinical conditions that may lead to PH, such as hypoxia, endothelial injury/inflammation, left-to-right shunt, or vascular obstruction. In several models of acute PH, such as acute hypoxia in rats Eddahibi et al 1995), pigs (Holm et al 1996), and piglets (Pearl et al 1999), cardiopulmonary bypass in pigs (Carteaux et al 1999), and endotoxic shock in pigs (Weitzberg et al 1996), bosentan blocked the progression of PH and increased cardiac output. The ET A antagonist, sitaxentan, demonstrated similar effects in hypoxic rats (Tilton et al 2000).…”

Section: Et Receptor Antagonism and Vascular/cardiac Hypertrophymentioning

confidence: 99%

Endothelin Receptor Antagonists

Clozel

Maresta

Humbert

2013

Handbook of Experimental Pharmacology

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Three pathways have been identified in the pathogenesis of pulmonary arterial hypertension (PAH): the endothelin (ET), nitric oxide (NO) and prostacyclin pathways. These pathways represent the targets of approved PAH therapies and their discovery has facilitated significant progress in the understanding and treatment of PAH. The ET system is well established as a key player in the pathophysiology of PAH, with deleterious effects mediated by both the ETA and ETB receptors. Endothelin receptor antagonists (ERAs) are an important part of PAH therapy, with two ERAs currently approved for the treatment of PAH and a novel ERA that has recently been investigated in a Phase III clinical trial. This chapter describes the role of ET in the pathogenesis of PAH, reviews experimental data and examines the clinical status of ERAs in PAH treatment.

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Acute pulmonary hypertension after cardiopulmonary bypass in pig: the role of endogenous endothelin

Cited by 23 publications

References 15 publications

ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

Endothelin-1 in Congenital Heart Disease

Endothelin Receptor Antagonists

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