Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat
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Wiley
2024
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| author | Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski |
| author_facet | Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski |
| collection | Wiley Open Access |
| contents | Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski British Journal of Pharmacology AbstractBackground and PurposePulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo‐inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline‐induced PH.Experimental approachRats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure‐volume loops were recorded and evaluated, myocardial pO2 was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.Key Results and ConclusionsITPP reduced PH‐related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor‐1α expression in RV cardiac myocytes but did not affect RV capillary density.ImplicationsOur study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy. 10.1111/bph.16482 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| doi_str_mv | 10.1111/bph.16482 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_bph_16482 |
| institution | Wiley Open Access |
| license_str_mv | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| publishDate | 2024 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski British Journal of Pharmacology Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat Marta Oknińska Aleksandra Paterek Małgorzata Grzanka Karolina Zajda Mateusz Surzykiewicz Filip Rolski Zuzanna Zambrowska Adam Torbicki Marcin Kurzyna Claudine Kieda Agnieszka Piekiełko‐Witkowska Michał Mączewski British Journal of Pharmacology AbstractBackground and PurposePulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo‐inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline‐induced PH.Experimental approachRats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure‐volume loops were recorded and evaluated, myocardial pO2 was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment.Key Results and ConclusionsITPP reduced PH‐related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor‐1α expression in RV cardiac myocytes but did not affect RV capillary density.ImplicationsOur study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy. 10.1111/bph.16482 http://onlinelibrary.wiley.com/termsAndConditions#vor |
| title | Myo‐inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline‐induced pulmonary hypertension in the rat |
| topic | British Journal of Pharmacology |
| url | https://bpspubs.onlinelibrary.wiley.com/doi/10.1111/bph.16482 |