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INHALED TEZOSENTAN REDUCES PULMONARY HYPERTENSION IN ENDOTOXIN-INDUCED LUNG INJURY
| Content Provider | Scilit |
|---|---|
| Author | Persson, Björn P. Rossi, Patrik Weitzberg, Eddie Oldner, Anders |
| Copyright Year | 2009 |
| Description | Journal: Shock The vasoconstrictive and proinflammatory peptide endothelin 1 (ET-1) is highly involved in the pathogenesis of sepsis and associated lung injury. Systemic administration of ET-receptor antagonists has been beneficial in experimental pulmonary hypertension. We wanted to study the effects of inhaled tezosentan, a dual endothelin-receptor antagonist on endotoxin-induced pulmonary hypertension, deterioration of gas exchange, and edema formation. After 2 h of endotoxemia, 28 anesthetized, mechanically ventilated pigs were randomized to either inhaled tezosentan 0.5 mg · kg−1 (TEZO0.5, n = 7), 0.05 mg · kg−1 (TEZO0.05, n = 7), intravenous 0.5 mg · kg−1 (TEZOiv, n = 7), or control (n = 7). Cardiopulmonary hemodynamics and gas-exchange parameters were recorded as well as extravascular lung water and pulmonary capillary pressure. In addition, plasma levels of tezosentan and ET-1 were analyzed. The protocol lasted for 5 h. Endotoxin-induced pulmonary hypertension (mean pulmonary artery pressure) was efficiently reduced by all treatments (TEZO0.5 24 ± 2, TEZO0.05 27 ± 2, TEZOiv 26 ± 1, and control 37 ± 2 mmHg at 4 h). TEZO0.5 and TEZOiv also reduced pulmonary capillary pressure. All treatments led to a modest reduction in extravascular lung water, whereas no effects were noted on oxygenation or systemic circulation. Despite similar effects on pulmonary hypertension systemic treatment resulted in significantly higher plasma levels of ET-1 (twofold) and tezosentan (10- to 100-fold). Inhalation of the dual ET-receptor antagonist tezosentan was feasible and efficiently counteracted endotoxin-induced pulmonary hypertension. These effects were obtained with only minor systemic uptake of tezosentan and without affecting circulating levels of plasma ET-1 as compared with intravenous administration. |
| Related Links | https://core.ac.uk/download/pdf/70340068.pdf |
| Ending Page | 434 |
| Page Count | 8 |
| Starting Page | 427 |
| ISSN | 15400514 |
| DOI | 10.1097/shk.0b013e31819e2cbb |
| Journal | Shock |
| Issue Number | 4 |
| Volume Number | 32 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2009-10-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Shock Peripheral Vascular Disease Reduced Pulmonary Induced Pulmonary Hypertension |
| Content Type | Text |
| Resource Type | Article |
| Subject | Emergency Medicine Critical Care and Intensive Care Medicine |
