PMID- 1644912
OWN - NLM
STAT- MEDLINE
DCOM- 19920909
LR  - 20181113
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 90
IP  - 2
DP  - 1992 Aug
TI  - Left ventricular systolic and diastolic dysfunction after infusion of tumor 
      necrosis factor-alpha in conscious dogs.
PG  - 389-98
AB  - We used a load-insensitive index of systolic left ventricular (LV) function and 
      an analysis of diastolic pressure-dimension relationships to test the hypothesis 
      that recombinant human (rh) tumor necrosis factor-alpha (TNF alpha) impairs LV 
      function in dogs. Animals were studied 7-10 d after aseptic implantation of 
      instrumentation to monitor cardiac output, external anterior-posterior LV 
      diameter, and LV and pleural pressures. Data were analyzed from seven dogs that 
      received active rhTNF alpha (100 micrograms/kg over 60 min) and from five dogs 
      that received heat-inactivated rhTNF alpha. At 24 h after infusion of active 
      rhTNF alpha, the slope of the LV end-diastolic dimension-stroke work relationship 
      decreased significantly, indicating a decrement in LV systolic contractility. 
      Simultaneously, LV unstressed dimension increased significantly, suggesting 
      diastolic myocardial creep. The end-diastolic relationship between LV transmural 
      pressure and normalized LV dimension (strain) was markedly displaced to the left, 
      suggesting increased diastolic elastic stiffness. Despite these changes in LV 
      performance, cardiac index was maintained by tachycardia. The abnormalities in LV 
      function were resolved by 72 h. We conclude that rhTNF alpha reversibly impairs 
      LV systolic and diastolic function in unanesthetized dogs. Because dysfunction 
      occurs greater than 6 h after the infusion of rhTNF alpha and persists for 24-48 
      h, the mechanism underlying this phenomenon may involve secondary mediators or a 
      change in myocardial gene expression.
FAU - Pagani, F D
AU  - Pagani FD
AD  - Department of Surgery, University of Massachusetts Medical Center, Worcester 
      01655.
FAU - Baker, L S
AU  - Baker LS
FAU - Hsi, C
AU  - Hsi C
FAU - Knox, M
AU  - Knox M
FAU - Fink, M P
AU  - Fink MP
FAU - Visner, M S
AU  - Visner MS
LA  - eng
GR  - R29 6M37631/PHS HHS/United States
GR  - R29 HL46280-01/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 58962-34-8 (6-Ketoprostaglandin F1 alpha)
SB  - IM
MH  - 6-Ketoprostaglandin F1 alpha/metabolism
MH  - Acid-Base Equilibrium
MH  - Animals
MH  - Blood Gas Analysis
MH  - Coronary Circulation/drug effects
MH  - Diastole/*drug effects
MH  - Dogs
MH  - Hemodynamics
MH  - Recombinant Proteins
MH  - Systole/*drug effects
MH  - Tumor Necrosis Factor-alpha/*adverse effects
MH  - Ventricular Function/*drug effects
PMC - PMC443113
EDAT- 1992/08/01 00:00
MHDA- 1992/08/01 00:01
PMCR- 1992/08/01
CRDT- 1992/08/01 00:00
PHST- 1992/08/01 00:00 [pubmed]
PHST- 1992/08/01 00:01 [medline]
PHST- 1992/08/01 00:00 [entrez]
PHST- 1992/08/01 00:00 [pmc-release]
AID - 10.1172/JCI115873 [doi]
PST - ppublish
SO  - J Clin Invest. 1992 Aug;90(2):389-98. doi: 10.1172/JCI115873.