Study of the Mechanism of Prostacyclin (PgI2) Action on Myocardial Contractility

Pavlović, Marija; Petkovic, D.; Cvetković, M; Zdjelar, K; Starčević, Vesna; Bosnić, Olivera

doi:10.1007/978-3-0348-7262-1_23

Cited by 5 publications

(5 citation statements)

References 4 publications

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“…Recently, we described for the fi rst time the positive inotropic effect of intravenous PGI 2 in an in vivo experimental model [11] , thereby confi rming previous in vitro data [9,10,17] . The main novel fi nding of the present study is that also inhalation of the aerosolized PGI 2 -analogs EPO and ILO increases myocardial contractility.…”

Section: Resultssupporting

confidence: 53%

“…A direct action of EPO and ILO on the cardiomyocyte could result from activation of a PGI 2 cyclase of the sarcolemma in the myocytes. Since experimental administration of ß-blockers in isolated ventricles was shown to notably reduce the positive inotropic effects of PGI 2 [17] , PGI 2 might also exert part of its inotropic action via ß-receptors, which are also located on the surface of the myocytes. Alternatively, the positive inotropic action of PGI 2 might result from a nerve stimulus generated locally in the lung in afferent autonomic sympathic nervous fi bers.…”

Section: Mechanism Of Actionmentioning

confidence: 99%

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Improved Ventricular Function during Inhalation of PGI<sub>2</sub> Aerosol Partly Relies on Enhanced Myocardial Contractility

Kemming

Kisch-Wedel²,

Flondor³

et al. 2005

Eur Surg Res

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Inhaled prostacyclin (PGI₂) aerosol induces selective pulmonary vasodilation. Further, it improves right ventricular (RV) function, which may largely rely on pulmonary vasodilation, but also on enhanced myocardial contractility. We investigated the effects of the inhaled PGI₂ analogs epoprostenol (EPO) and iloprost (ILO) on RV function and myocardial contractility in 9 anesthetized pigs receiving aerosolized EPO (25 and 50 ng·kg^–1·min^–1) and, consecutively, ILO (60 ng·kg^–1·min^–1) for 20 min each. We measured pulmonary artery pressure (PAP), RV ejection fraction (RVEF) and RV end-diastolic-volume (RV-EDV), and left ventricular end-systolic pressure-volume-relation (end-systolic elastance, E_es). EPO and ILO reduced PAP, increased RVEF and reduced RVEDV. E_es was enhanced during all doses tested, which reached statistical significance during EPO_25ng and ILO, but not during EPO_50ng. PGI₂ aerosol enhances myocardial contractility in healthy pigs, contributing to improve RV function.

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Section: Resultssupporting

confidence: 53%

Section: Mechanism Of Actionmentioning

confidence: 99%

Improved Ventricular Function during Inhalation of PGI<sub>2</sub> Aerosol Partly Relies on Enhanced Myocardial Contractility

Kemming

Kisch-Wedel²,

Flondor³

et al. 2005

Eur Surg Res

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“…Although RVSWI and PC increased post-therapy in the cohort as a whole, this finding was driven by an increase in RVSWI and PC in the 21 patients started on prostanoid only therapy. Potential explanations for this difference include greater efficacy of prostanoids in therapy of PAH pulmonary vascular disease, a direct effect of prostaglandins on the right ventricle (16,17), or differences in treatment as a function of disease severity reflected in RVSWI or other unfavorable hemodynamic predictors. The strong influence we found of stroke volume on change in RVSWI suggests that prostanoids may exert an inotropic effect on the RV, but this requires further study.…”

Section: Discussionmentioning

confidence: 99%

Prostanoids But Not Oral Therapies Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Brittain

Pugh

Wheeler

et al. 2013

JACC: Heart Failure

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Objectives We hypothesized that RV stroke work index (RVSWI) and pulmonary capacitance (PC) would increase after treatment for pulmonary arterial hypertension (PAH) and that prostanoids would have a stronger effect than oral therapy. Background Right ventricular (RV) function is a major determinant of outcome in patients with PAH. Little is known about the response of RV function or its hemodynamic determinants to PAH-specific therapy. Methods We reviewed hemodynamic and health data on 58 patients from an institutional registry and analyzed changes in hemodynamics between diagnostic and first repeat catheterization after initiation of therapy for PAH. Results RVSWI and PC increased significantly after therapy (p = 0.007 and 0.02, respectively). Improvement in RV function was limited to patients treated with prostanoid-only therapy (p = 0.04); no improvement was found in patients treated with oral therapy (p = 0.25). Patients with the poorest baseline RV function (lowest tertile) had the greatest improvement post-therapy (p = 0.005 and < 0.001 vs. middle and highest tertiles). The major determinant of RVSWI was change in stroke volume (rs = 0.54, p < 0.001), indicating RVSWI is an accurate reflection of RV function. Conclusion RV function improves after therapy with regimens including prostanoids but not oral-only regimens. Patients with the least compensated RV function at diagnosis may derive the most benefit from therapy. Larger studies are needed to determine whether changes in RVSWI after therapy are associated with outcomes.

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“…The synergistic effect of a combination of treprostinil and isoprenaline was previously reported by many studies in cardiac tissues and cells [28,[49][50][51][52][53]. We wanted to investigate the effect in the setting of established PH-associated RV maladaptive remodelling.…”

Section: Discussionmentioning

confidence: 94%

Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function

Judina,

Niglas,

Leonov

et al. 2023

Cells

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(1) Pulmonary hypertension (PH)-associated right ventricular (RV) failure is linked to a reduction in pulmonary vasodilators. Treprostinil has shown effectiveness in PAH patients with cardiac decompensation, hinting at potential cardiac benefits. We investigated treprostinil’s synergy with isoprenaline in RV and LV cardiomyocytes. We hypothesised that disease-related RV structural changes in cardiomyocytes would reduce contractile responses and cAMP/PKA signalling activity. (2) We induced PH in male Sprague Dawley rats using monocrotaline and isolated their ventricular cardiomyocytes. The effect of in vitro treprostinil and isoprenaline stimulation on contraction was assessed. FRET microscopy was used to study PKA activity associated with treprostinil stimulation in AKAR3-NES FRET-based biosensor-expressing cells. (3) RV cells exhibited maladaptive remodelling with hypertrophy, impaired contractility, and calcium transients compared to control and LV cardiomyocytes. Combining treprostinil and isoprenaline failed to enhance inotropy in PH RV cardiomyocytes. PH RV cardiomyocytes displayed an aberrant contractile behaviour, which the combination treatment could not rectify. Finally, we observed decreased PKA activity in treprostinil-treated PH RV cardiomyocytes. (4) PH-associated RV cardiomyocyte remodelling reduced treprostinil sensitivity, inotropic support, and impaired relaxation. Overall, this study highlights the complexity of RV dysfunction in advanced PH and suggests the need for alternative therapeutic strategies.

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Study of the Mechanism of Prostacyclin (PgI2) Action on Myocardial Contractility

Cited by 5 publications

References 4 publications

Improved Ventricular Function during Inhalation of PGI<sub>2</sub> Aerosol Partly Relies on Enhanced Myocardial Contractility

Improved Ventricular Function during Inhalation of PGI<sub>2</sub> Aerosol Partly Relies on Enhanced Myocardial Contractility

Prostanoids But Not Oral Therapies Improve Right Ventricular Function in Pulmonary Arterial Hypertension

Pulmonary Hypertension-Associated Right Ventricular Cardiomyocyte Remodelling Reduces Treprostinil Function

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