Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism
Abstract Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodil...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-02-01
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| Series: | Pharmacology Research & Perspectives |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/prp2.462 |
| _version_ | 1819044697231851520 |
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| author | Kristofer F. Nilsson Lars E. Gustafsson |
| author_facet | Kristofer F. Nilsson Lars E. Gustafsson |
| author_sort | Kristofer F. Nilsson |
| collection | DOAJ |
| description | Abstract Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodilator, the organic mononitrites of 1,2‐propanediol (PDNO), in a rabbit model of acute pulmonary embolism. In anesthetized and ventilated rabbits, systemic and pulmonary hemodynamics, exhaled nitric oxide (NO), plasma nitrite concentration, and blood gases were monitored. First, dose–response experiments with intravenous and left heart ventricle infusions of PDNO and inorganic nitrite were done in naive animals and in pulmonary hypertension induced by a thromboxane A2 analogue. Second, acute pulmonary embolism was induced and either PDNO or placebo were administered intravenously within 20 minutes and evaluated within 1 hour after pulmonary embolization. PDNO intravenously, in contrast to inorganic nitrite intravenously, increased exhaled NO and counteracted pulmonary hypertension and vasodilated the systemic circulation, dose‐dependently, thereby showing efficient NO donation. Pulmonary embolization induced pulmonary hypertension and gas exchange disturbances. PDNO significantly decreased and normalized pulmonary vascular resistance and the right ventricle rate‐pressure product, without causing tolerance, with no significant side effects on the systemic circulation, nor on blood‐gas values or on methemoglobin formation. In conclusion, PDNO is a NO donor and an efficient vasodilator in the pulmonary circulation. Treatment with this or similar organic nitrites intravenously may be a future option to avoid right heart failure in life‐threatening acute pulmonary embolism. |
| first_indexed | 2024-12-21T10:16:48Z |
| format | Article |
| id | doaj.art-166b742bb9564c9d8a975218094d3b8b |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-12-21T10:16:48Z |
| publishDate | 2019-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-166b742bb9564c9d8a975218094d3b8b2022-12-21T19:07:33ZengWileyPharmacology Research & Perspectives2052-17072019-02-0171n/an/a10.1002/prp2.462Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolismKristofer F. Nilsson0Lars E. Gustafsson1Department of Physiology and Pharmacology Karolinska Institute Stockholm SwedenDepartment of Physiology and Pharmacology Karolinska Institute Stockholm SwedenAbstract Acute pulmonary embolism may cause right heart failure due to increased pulmonary vascular resistance and arterial hypoxemia. Effective vasodilator therapy of the pulmonary hypertension is highly needed. Therefore, we investigated the effects of a newly developed effective pulmonary vasodilator, the organic mononitrites of 1,2‐propanediol (PDNO), in a rabbit model of acute pulmonary embolism. In anesthetized and ventilated rabbits, systemic and pulmonary hemodynamics, exhaled nitric oxide (NO), plasma nitrite concentration, and blood gases were monitored. First, dose–response experiments with intravenous and left heart ventricle infusions of PDNO and inorganic nitrite were done in naive animals and in pulmonary hypertension induced by a thromboxane A2 analogue. Second, acute pulmonary embolism was induced and either PDNO or placebo were administered intravenously within 20 minutes and evaluated within 1 hour after pulmonary embolization. PDNO intravenously, in contrast to inorganic nitrite intravenously, increased exhaled NO and counteracted pulmonary hypertension and vasodilated the systemic circulation, dose‐dependently, thereby showing efficient NO donation. Pulmonary embolization induced pulmonary hypertension and gas exchange disturbances. PDNO significantly decreased and normalized pulmonary vascular resistance and the right ventricle rate‐pressure product, without causing tolerance, with no significant side effects on the systemic circulation, nor on blood‐gas values or on methemoglobin formation. In conclusion, PDNO is a NO donor and an efficient vasodilator in the pulmonary circulation. Treatment with this or similar organic nitrites intravenously may be a future option to avoid right heart failure in life‐threatening acute pulmonary embolism.https://doi.org/10.1002/prp2.462alkyl nitriteschromatographyhigh pressure liquidhypertensioninorganic nitritelung |
| spellingShingle | Kristofer F. Nilsson Lars E. Gustafsson Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism Pharmacology Research & Perspectives alkyl nitrites chromatography high pressure liquid hypertension inorganic nitrite lung |
| title | Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| title_full | Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| title_fullStr | Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| title_full_unstemmed | Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| title_short | Treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| title_sort | treatment with new organic nitrites in pulmonary hypertension of acute experimental pulmonary embolism |
| topic | alkyl nitrites chromatography high pressure liquid hypertension inorganic nitrite lung |
| url | https://doi.org/10.1002/prp2.462 |
| work_keys_str_mv | AT kristoferfnilsson treatmentwithneworganicnitritesinpulmonaryhypertensionofacuteexperimentalpulmonaryembolism AT larsegustafsson treatmentwithneworganicnitritesinpulmonaryhypertensionofacuteexperimentalpulmonaryembolism |