Endothelin Receptor Inhibitors Decrease Contractility in the Hypertrophied Right Ventricle.

Nagendran, Jayan; Sutendra, Gopinath; Haromy, Alois; Dz, Fu; Db, Ross; Rebeyka, IM; Michelakis, ED

doi:10.1164/ajrccm-conference.2009.179.1_meetingabstracts.a4141

Cited by 2 publications

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“…The therapies outlined above may improve right-ventricular function to the extent that they decrease right-ventricular afterload, although emerging data suggest that some of these therapies, such as PDE5 inhibition and ET-1 receptor antagonism, may also enhance or impair (respectively) contractility of the hypertrophied right ventricle. 113,230 However, in addition to afterload reduction, other therapies that support the right ventricle may be necessary, especially in acute care settings.…”

Section: Support Of Right-ventricular Functionmentioning

confidence: 99%

Advances in the Management of Pediatric Pulmonary Hypertension

2011

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Pulmonary hypertension is a rare disease in neonates, infants, and children, and is associated with substantial morbidity and mortality. An adequate understanding of the controlling pathophysiologic mechanisms is lacking. Moreover, a minority of research is focused specifically on neonatal and pediatric populations. Although therapeutic options have increased over the past several decades, they remain limited. In advanced pulmonary hypertension, progressive pulmonary vascular functional and structural changes ultimately cause increased pulmonary vascular impedance, rightventricular failure, and death. Management includes the prevention and/or treatment of active pulmonary vasoconstriction, the support of right-ventricle function, treatment of the underlying disease (if possible), and the promotion of regressive remodeling of structural pulmonary vascular changes. Most currently available therapies augment or inhibit factors, or mediators of their downstream signaling cascades, that originate in the pulmonary vascular endothelium. These pathways include nitric-oxide/cyclic guanosine monophosphate (cGMP), prostacyclin, and endothelin-1. The ability to reverse advanced structural changes remains an as yet unattained goal. This paper reviews the epidemiology, pathophysiology, current treatments, and emerging therapies related to neonatal and pediatric pulmonary hypertension.

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Section: Support Of Right-ventricular Functionmentioning

confidence: 99%

Advances in the Management of Pediatric Pulmonary Hypertension

2011

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“…However, it is worth noting that the ERAs have not been shown to have a beneficial effect on right-heart function, and emerging evidence suggested that ET receptors are upregulated in the hypertrophied right ventricle and decrease contractility in the Langendorf preparation of right ventricle in the rat (49).…”

Section: Endothelin Receptor Antagonistsmentioning

confidence: 99%

The role of calcium channel blockers, steroids, anticoagulation, antiplatelet drugs, and endothelin receptor antagonists

Adatia

Shekerdemian

2010

Pediatric Critical Care Medicine

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The rationale for the drug therapy of pulmonary artery hypertension is to reduce mortality and morbidity caused by failure of right ventricular adaptation to an elevated pulmonary vascular resistance. We review the evidence for the use of calcium-channel blockers, steroids, anticoagulation, antiplatelet drugs, and endothelin receptor antagonists in the management of pulmonary artery hypertension. The drugs we discuss are more suited to long-term outpatient therapy. These drugs have not found a routine place in intensive care management, and calcium-channel blockers are contraindicated in patients with right-heart failure. The efficacy of many agents has been extrapolated from data acquired in adult patients and applied to children. All of us involved in the care of young patients with pulmonary artery hypertension should advocate for both the inclusion of younger patients in clinical trials and the design of distinctly pediatric trials with pharmaceutical and drug administration agencies. It is only with data derived from pediatric inclusive studies that we shall be able to recommend therapy with strong evidence. However, it is important to point out that the use of newer agents for the treatment of chronic pulmonary artery hypertension (prostacyclin, endothelin receptor antagonists, nitric oxide, and sildenafil) have not been shown to improve survival unequivocally and have relied on surrogates, such as exercise capacity. There are no long-term studies of survival benefit. Recent studies have included data on time to clinical worsening, which may be a more predictive surrogate of survival.

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Endothelin Receptor Inhibitors Decrease Contractility in the Hypertrophied Right Ventricle.

Cited by 2 publications

References 0 publications

Advances in the Management of Pediatric Pulmonary Hypertension

Advances in the Management of Pediatric Pulmonary Hypertension

The role of calcium channel blockers, steroids, anticoagulation, antiplatelet drugs, and endothelin receptor antagonists

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