Tumor necrosis factor-alpha causes myocardial depression in guinea pigs.
METHODS
Tumor necrosis factor-alpha (TNF-alpha) is an important mediator of metabolic and cardiovascular derangements in sepsis and endotoxicosis. We tested the hypothesis that TNF-alpha 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-alpha (1 mg/kg). At 6, 24, or 72 hrs after injection, atria were harvested, split, connected to force displacement x transducer-amplifier-recorder systems and maintained in vitro in oxygenated 37.5 degrees C Krebs-Henseleit buffer.


RESULTS
Maximal left atrial force of contraction and maximal left atrial velocity of contraction were decreased in the TNF-alpha treated animals compared with controls (p less than .05), irrespective of time after TNF-alpha 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-alpha treated animals compared with controls (p less than .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-alpha injected in vivo causes in vitro myocardial depression and alters cardiac responsiveness to norepinephrine.
Heard
S O
SO
Department of Anesthesiology, University of Massachusetts Medical Center, Worcester.
Perkins
M W
MW
Fink
M P
MP
D000704:Analysis of Variance; D000818:Animals; D003864:Depression, Chemical; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D009638:Norepinephrine