Laboratory Investigations: PDF OnlyTumor necrosis factor-α causes myocardial depression in guinea pigsHEARD, STEPHEN O. MD, FCCM; PERKINS, MICHAEL W. BS; FINK, MITCHELL P. MD, FCCMAuthor Information From the Departments of Anesthesiology and Surgery, University of Massachusetts Medical Center, Worcester, MA. Critical Care Medicine: April 1992 - Volume 20 - Issue 4 - p 523-527 Buy Abstract Background and Methods Tumor necrosis factor-α (TNF-α) is an important mediator of metabolic and cardiovascular derangements in sepsis and endotoxicosis. We tested the hypothesis that TNF-α causes myocardial depression and alters the cardiac responsiveness to administered norepinephrine. Albino Hartley guinea pigs (n = 32) of either sex were injected iv with saline (1.5 mL) or recombinant human TNF-α (1 mg/kg). At 6, 24, or 72 hrs after injection, atria were harvested, split, connected to force displacement × transducer-amplifier-recorder systems and maintained in vitro in oxygenated 37.5°C Krebs-Henseleit buffer. Results Maximal left atrial force of contraction and maximal left atrial velocity of contraction were decreased in the TNF-a treated animals compared with controls (p <.05), irrespective of time after TNF-α injection. There were no differences between groups for left atrial maximal velocity of relaxation and right atrial rate. The norepinephrine concentration that elicited a 50% maximal left atrial contractile response (ED50) was higher in TNF-α treated animals compared with controls (p <.05). Maximal left atrial force of contraction, maximal right atrial rate, and right atrial ED50 were similar in the two groups. Conclusions These results indicate that TNF-α injected in vivo causes in vitro myocardial depression and alters cardiac responsiveness to norepinephrine. (Crit Care Med 1992; 20:523–527) © Williams & Wilkins 1992. All Rights Reserved.