UMMS Affiliation

Department of Surgery

Publication Date


Document Type



6-Ketoprostaglandin F1 alpha; Acid-Base Equilibrium; Animals; Blood Gas Analysis; Coronary Circulation; Diastole; Dogs; Hemodynamics; Recombinant Proteins; Systole; Tumor Necrosis Factor-alpha; Ventricular Function


Cardiology | Surgery


We used a load-insensitive index of systolic left ventricular (LV) function and an analysis of diastolic pressure-dimension relationships to test the hypothesis that recombinant human (rh) tumor necrosis factor-alpha (TNF alpha) impairs LV function in dogs. Animals were studied 7-10 d after aseptic implantation of instrumentation to monitor cardiac output, external anterior-posterior LV diameter, and LV and pleural pressures. Data were analyzed from seven dogs that received active rhTNF alpha (100 micrograms/kg over 60 min) and from five dogs that received heat-inactivated rhTNF alpha. At 24 h after infusion of active rhTNF alpha, the slope of the LV end-diastolic dimension-stroke work relationship decreased significantly, indicating a decrement in LV systolic contractility. Simultaneously, LV unstressed dimension increased significantly, suggesting diastolic myocardial creep. The end-diastolic relationship between LV transmural pressure and normalized LV dimension (strain) was markedly displaced to the left, suggesting increased diastolic elastic stiffness. Despite these changes in LV performance, cardiac index was maintained by tachycardia. The abnormalities in LV function were resolved by 72 h. We conclude that rhTNF alpha reversibly impairs LV systolic and diastolic function in unanesthetized dogs. Because dysfunction occurs greater than 6 h after the infusion of rhTNF alpha and persists for 24-48 h, the mechanism underlying this phenomenon may involve secondary mediators or a change in myocardial gene expression.

DOI of Published Version



J Clin Invest. 1992 Aug;90(2):389-98. Link to article on publisher's site

Journal/Book/Conference Title

The Journal of clinical investigation

Related Resources

Link to Article in PubMed

PubMed ID