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Published on: December 5, 2011
Tumor necrosis factor and cardiac function
J E DeMeules1, F A Pigula, M Mueller
1Department of Surgery, University of Vermont College of Medicine, Burlington.
Abstract:
The direct effect of tumor necrosis factor (TNF), a product of activated macrophages, on myocardial performance was determined using an isolated papillary muscle technique and a modified Langendorff preparation. Papillary muscle was obtained from male adult rats 4-5 hours after they received either 100 ng/kg TNF (group A), or 100 micrograms/kg TNF (group B) or saline (control). Group B animals exhibited significantly greater peak tension development and velocity of contraction compared with controls (p less than 0.05). In group A animals these variables were not significantly different from those of the controls (p greater than 0.05). Electrophysiologic measurements revealed a significant decrease in resting membrane potential in both group A and group B animals compared with the controls (p less than 0.05). Whole hearts perfused with serum from animals treated with TNF 18-22 hours earlier exhibited significant impairment of contractility, decreased rate of systolic pressure development, and decreased rate of relaxation compared with the controls (p less than 0.05). Coronary flow and myocardial water content were similar for both groups of perfused hearts. These data suggest that tumor necrosis factor stimulates an early beneficial effect on myocardial function, which 18-22 hours later is associated with impairment of myocardial performance. This effect appears to be serum transferable.
Insights
Tumor necrosis factor (TNF) initially enhances heart muscle function. However, this effect is followed by impaired myocardial performance 18-22 hours later, transferable via serum.
Area of Science:
- Cardiology
- Immunology
- Physiology
Background:
- Tumor necrosis factor (TNF) is a cytokine produced by activated macrophages.
- The impact of TNF on myocardial performance requires further investigation.
Purpose of the Study:
- To determine the direct effects of TNF on myocardial performance.
- To investigate the time-dependent changes in cardiac function following TNF administration.
Main Methods:
- Isolated papillary muscle technique in rats.
- Modified Langendorff preparation for whole-heart perfusion.
- Administration of varying doses of TNF and saline as control.
Main Results:
- High-dose TNF (100 µg/kg) significantly increased peak tension and contraction velocity.
- Both TNF doses decreased resting membrane potential.
- Serum from TNF-treated animals impaired contractility, systolic pressure development, and relaxation 18-22 hours post-treatment.
Conclusions:
- TNF exerts an early beneficial effect on myocardial function.
- A later impairment of myocardial performance is observed, suggesting a time-dependent biphasic effect.
- The later detrimental effect is transferable via serum.
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