PMID- 8227345
OWN - NLM
STAT- MEDLINE
DCOM- 19931210
LR  - 20220317
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 92
IP  - 5
DP  - 1993 Nov
TI  - Cellular basis for the negative inotropic effects of tumor necrosis factor-alpha 
      in the adult mammalian heart.
PG  - 2303-12
AB  - To define the mechanism(s) responsible for the negative inotropic effects of 
      tumor necrosis factor-alpha (TNF alpha) in the adult heart, we examined the 
      functional effects of TNF alpha in the intact left ventricle and the isolated 
      adult cardiac myocyte. Studies in both the ventricle and the isolated adult 
      cardiac myocyte showed that TNF alpha exerted a concentration- and time-dependent 
      negative inotropic effect that was fully reversible upon removal of this 
      cytokine. Further, treatment with a neutralizing anti-TNF alpha antibody 
      prevented the negative inotropic effects of TNF alpha in isolated myocytes. A 
      cellular basis for the above findings was provided by studies which showed that 
      treatment with TNF alpha resulted in decreased levels of peak intracellular 
      calcium during the systolic contraction sequence; moreover, these findings did 
      not appear to be secondary to alterations in the electrophysiological properties 
      of the cardiac myocyte. Further studies showed that increased levels of nitric 
      oxide, de novo protein synthesis, and metabolites of the arachidonic acid pathway 
      were unlikely to be responsible for the TNF alpha-induced abnormalities in 
      contractile function. Thus, these studies constitute the initial demonstration 
      that the negative inotropic effects of TNF alpha are the direct result of 
      alterations in intracellular calcium homeostasis in the adult cardiac myocyte.
FAU - Yokoyama, T
AU  - Yokoyama T
AD  - Department of Medicine, Veterans Affairs Medical Center, Houston, Texas 77030.
FAU - Vaca, L
AU  - Vaca L
FAU - Rossen, R D
AU  - Rossen RD
FAU - Durante, W
AU  - Durante W
FAU - Hazarika, P
AU  - Hazarika P
FAU - Mann, D L
AU  - Mann DL
LA  - eng
GR  - HL-41408/HL/NHLBI NIH HHS/United States
GR  - HL-42550/HL/NHLBI NIH HHS/United States
GR  - K08HL-02010/HL/NHLBI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - Blood Pressure/drug effects
MH  - Calcium/*metabolism
MH  - Cats
MH  - Cell Separation
MH  - Cell Survival
MH  - Electrophysiology
MH  - Heart Ventricles/*drug effects
MH  - Homeostasis/drug effects
MH  - Myocardial Contraction/*drug effects
MH  - Myocardium/cytology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
PMC - PMC288411
EDAT- 1993/11/01 00:00
MHDA- 1993/11/01 00:01
PMCR- 1993/11/01
CRDT- 1993/11/01 00:00
PHST- 1993/11/01 00:00 [pubmed]
PHST- 1993/11/01 00:01 [medline]
PHST- 1993/11/01 00:00 [entrez]
PHST- 1993/11/01 00:00 [pmc-release]
AID - 10.1172/JCI116834 [doi]
PST - ppublish
SO  - J Clin Invest. 1993 Nov;92(5):2303-12. doi: 10.1172/JCI116834.