PMID- 1559367 OWN - NLM STAT- MEDLINE DCOM- 19920508 LR - 20190706 IS - 0090-3493 (Print) IS - 0090-3493 (Linking) VI - 20 IP - 4 DP - 1992 Apr TI - Tumor necrosis factor-alpha causes myocardial depression in guinea pigs. PG - 523-7 AB - BACKGROUND AND 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. FAU - Heard, S O AU - Heard SO AD - Department of Anesthesiology, University of Massachusetts Medical Center, Worcester. FAU - Perkins, M W AU - Perkins MW FAU - Fink, M P AU - Fink MP LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Crit Care Med JT - Critical care medicine JID - 0355501 RN - 0 (Recombinant Proteins) RN - 0 (Tumor Necrosis Factor-alpha) RN - X4W3ENH1CV (Norepinephrine) SB - IM MH - Analysis of Variance MH - Animals MH - Depression, Chemical MH - Female MH - Guinea Pigs MH - Heart Rate/*drug effects MH - In Vitro Techniques MH - Male MH - Myocardial Contraction/*drug effects MH - Norepinephrine/pharmacology MH - Recombinant Proteins/pharmacology MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 1992/04/01 00:00 MHDA- 1992/04/01 00:01 CRDT- 1992/04/01 00:00 PHST- 1992/04/01 00:00 [pubmed] PHST- 1992/04/01 00:01 [medline] PHST- 1992/04/01 00:00 [entrez] AID - 10.1097/00003246-199204000-00015 [doi] PST - ppublish SO - Crit Care Med. 1992 Apr;20(4):523-7. doi: 10.1097/00003246-199204000-00015.