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Vesnarinone and amrinone reduce the systemic inflammatory response syndrome
K Takeuchi1, P J del Nido, A E Ibrahim
1Department of Cardiac Surgery and the Anesthesiology/ Critical Care Medicine Laboratory, Children's Hospital and Harvard Medical School, Boston, Mass. 02115, USA.
The Journal of Thoracic and Cardiovascular Surgery
|January 27, 1999
Summary
Vesnarinone and amrinone reduced inflammation and cardiac dysfunction in endotoxin-activated rabbits. Vesnarinone notably decreased mortality and fever, suggesting therapeutic potential for systemic inflammatory response.
Area of Science:
- Cardiovascular Pharmacology
- Inflammatory Response
- Sepsis Models
Background:
- Systemic inflammatory response is a key driver of organ dysfunction.
- Clinically used agents amrinone and vesnarinone possess inotropic and vasodilating properties.
Purpose of the Study:
- To test if amrinone and vesnarinone decrease inflammation and cardiac dysfunction.
- To evaluate their efficacy in a rabbit model of endotoxin-induced systemic inflammation.
Main Methods:
- Rabbits received intravenous endotoxin, with or without amrinone or vesnarinone.
- Systemic effects (mortality, fever, acidosis) and inflammatory markers (cytokines, myeloperoxidase, nitric oxide synthase) were assessed.
- Cardiac function was evaluated in Langendorff-perfused hearts.
Main Results:
- Vesnarinone significantly reduced mortality (19% vs. 61%) and acidosis.
- Both agents decreased plasma tumor necrosis factor-alpha and interleukin-1 beta.
- Both agents improved myocardial systolic and diastolic function and reduced inducible nitric oxide synthase activity.
Conclusions:
- Vesnarinone and amrinone show potential in limiting inflammatory activation and organ dysfunction.
- Vesnarinone demonstrated additional benefits, including reduced fever and lung leukocyte infiltration.
- Pharmacokinetic and structure-activity relationships may influence tissue-specific inflammatory signaling inhibition.