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Tumor necrosis factor challenges in canines: patterns of cardiovascular dysfunction
P W Eichenholz1, P Q Eichacker, W D Hoffman
1Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
The American Journal of Physiology
|September 1, 1992
Summary
Tumor necrosis factor (TNF) infusion in canines caused dose-dependent increases in mortality and cardiac dysfunction. While initial cardiac dysfunction severity was similar across doses, recovery time was prolonged with higher TNF doses.
Area of Science:
- Cardiovascular Physiology
- Immunology
- Toxicology
Background:
- Tumor necrosis factor (TNF) is a pro-inflammatory cytokine implicated in various physiological and pathological processes.
- Understanding the cardiovascular effects of TNF is crucial for managing inflammatory conditions and sepsis.
Purpose of the Study:
- To investigate the dose-dependent cardiovascular effects and mortality associated with human recombinant TNF infusion in conscious canines.
- To determine the time course of cardiac dysfunction and recovery following TNF administration.
Main Methods:
- Conscious canines received varying intravenous doses of human recombinant TNF (0, 30, 60, 120 µg/kg) over 1 hour.
- Cardiovascular parameters, including left ventricular ejection fraction (LVEF), were monitored for 10 days.
- Mortality rates and cardiac function recovery were assessed in relation to TNF dosage.
Main Results:
- Mortality increased significantly with higher TNF doses (P < 0.025).
- Left ventricular ejection fraction (LVEF) decreased in all TNF-treated groups at 2 hours post-infusion, with the highest dose showing the greatest reduction.
- Cardiac dysfunction severity at 8 hours was independent of TNF dose, but recovery time was dose-dependent, with higher doses leading to prolonged abnormalities up to 240 hours.
Conclusions:
- TNF administration induces significant cardiovascular abnormalities and mortality in a dose-dependent manner.
- While acute cardiac dysfunction severity may be similar, the duration of cardiac impairment is directly related to the TNF dose.
- These findings highlight the critical role of TNF in mediating cardiac dysfunction and underscore the importance of dose-response relationships in its toxicological effects.