PMID- 8603499
OWN - NLM
STAT- MEDLINE
DCOM- 19960516
LR  - 20190706
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 78
IP  - 1
DP  - 1996 Jan
TI  - Tumor necrosis factor-alpha induces a biphasic effect on myocardial contractility 
      in conscious dogs.
PG  - 154-60
AB  - Tumor necrosis factor-alpha (TNF-alpha) likely plays a role in the 
      pathophysiology of myocardial depression observed in septic shock. To evaluate 
      the hemodynamic effects of TNF-alpha in vivo while eliminating the influence of 
      altered sympathetic tone, eight conscious chronically instrumented dogs were 
      studied after pretreatment with propranolol (2 mg/kg) and atropine (2mg). Using 
      three sets of piezoelectric crystals to measure left ventricular (LV) volume and 
      LV manometers to measure pressure, we determined load-independent parameters of 
      LV systolic performance before, during, and after infusion of recombinant human 
      TNF-alpha (rhTNF-alpha, 40 micrograms/kg for 1 hour). Plasma was analyze for 
      epinephrine and norepinephrine. Between 1 and 7 hours of exposure, rhTNF-alpha 
      induced significant increases in circulating catecholamines. Norepinephrine rose 
      from 268.6 +/- 47.2 to 426.2 +/- 87.0 pg/mL (P < .05) at 1 hour and peaked at 
      921.2 +/- 156.8 pg/mL (P < .001) at 4 hours after initiating rhTNF-alpha 
      treatment. Similarly, epinephrine increased from 130.2 +/- 30.9 to 884.5 +/- 
      210.2 pg/mL (P < .05) at 1 hour and peaked at 3195.3 +/- 476 pg/mL (P < .001) at 
      4 hours. Before the surge of circulating catecholamines and despite complete beta 
      adrenergic blockade, rhTNF-alpha induced a 7% to 40% increase in LV contractile 
      performance during the 60-minute infusion. After this initial positive inotropic 
      effect, rhTNF-alpha treatment led to precipitous systolic dysfunction between 2 
      and 7 hours of exposure; this myocardial depressant effect persisted at 25 hours. 
      LV systolic performance declined to 19% to 35% of baseline values, depending on 
      the specific contractile parameter evaluated. We conclude that rhTNF-alpha 
      affects LV systolic function in a time-dependent biphasic manner. Increases in 
      circulating catecholamines after rhTNF-alpha infusion cannot account for the 
      early improvement in LV systolic performance.
FAU - Murray, D R
AU  - Murray DR
AD  - Department of Medicine, University of Texas Health Science Center at San Antonio, 
      USA.
FAU - Freeman, G L
AU  - Freeman GL
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Catecholamines)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - Catecholamines/blood
MH  - Dogs
MH  - Myocardial Contraction/*drug effects/physiology
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Ventricular Function, Left/drug effects/physiology
EDAT- 1996/01/01 00:00
MHDA- 1996/01/01 00:01
CRDT- 1996/01/01 00:00
PHST- 1996/01/01 00:00 [pubmed]
PHST- 1996/01/01 00:01 [medline]
PHST- 1996/01/01 00:00 [entrez]
AID - 10.1161/01.res.78.1.154 [doi]
PST - ppublish
SO  - Circ Res. 1996 Jan;78(1):154-60. doi: 10.1161/01.res.78.1.154.