PMID- 7668305
OWN - NLM
STAT- MEDLINE
DCOM- 19951010
LR  - 20190717
IS  - 0002-9629 (Print)
IS  - 0002-9629 (Linking)
VI  - 310
IP  - 3
DP  - 1995 Sep
TI  - Delayed thromboxane or tumor necrosis factor-alpha, but not leukotriene 
      inhibition, attenuates prolonged pulmonary hypertension in endotoxemia.
PG  - 103-10
AB  - The early phase of endotoxin-induced acute hemodynamic disturbances and hypoxemia 
      is mediated by various factors, including eicosanoids and tumor necrosis 
      factor-alpha (TNF alpha). Thromboxane A2 is the major mediator of the early 
      pulmonary hypertension associated with endotoxemia, but the mechanisms underlying 
      the prolonged hemodynamic disturbances observed in ongoing endotoxemia are not 
      well understood. The authors used a chronically instrumental young piglet model 
      to determine the roles of several eicosanoids and of TNF alpha in the prolonged 
      endotoxin-induced pulmonary hypertension and other cardiovascular derangements. 
      Animals were given 40 micrograms/kg endotoxin intravenously per hour for 30 
      minutes, followed by 20 micrograms/kg per hour. In all animals, persistent 
      pulmonary hypertension, lowered cardiac output, any hypoxemia developed during 
      endotoxin infusion. After 3 hours of endotoxin infusion, randomly ordered 
      infusions of 1 mg/kg dazmegrel (a thromboxane A2 synthesis inhibitor), 5mg/kg 
      nordihydroguaiaretic acid (a 5-lipoxygenase inhibitor), and 20 mg/kg 
      pentoxifylline (A TNF alpha inhibitor) were given intravenously at 
      30-to-60-minute intervals. Dazmegrel and pentoxifylline lowered pulmonary 
      arterial pressure and resistance and raised arterial oxygen tension. Cardiac 
      output increased significantly after pentoxifylline. These hemodynamic effects 
      persisted for 30-60 minutes, despite continued endotoxin infusion. The elevated 
      plasma concentrations of thromboxane B2 and TNF alpha returned toward 
      preendotoxin baseline values after dazmegrel and pentoxifylline treatment, 
      respectively. No beneficial effects were noted after administration of 
      nordihydroguaiaretic acid. Based on these results, both thromboxane A2 and TNF 
      alpha, but not 5-lipoxygenase products, play active roles in prolonged 
      endotoxin-induced pulmonary hypertension and hypoxemia in young piglets. Combined 
      thromboxane A2 and TNF alpha blockade may be clinically useful in treatment of 
      advanced sepsis in neonates.
FAU - Li, J X
AU  - Li JX
AD  - Department of Pediatrics, University of Alabama at Birmingham 35233-7335, USA.
FAU - Oliver, J R
AU  - Oliver JR
FAU - Lu, C Y
AU  - Lu CY
FAU - Philips, J B 3rd
AU  - Philips JB 3rd
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Med Sci
JT  - The American journal of the medical sciences
JID - 0370506
RN  - 0 (Endotoxins)
RN  - 0 (Imidazoles)
RN  - 0 (Leukotriene Antagonists)
RN  - 0 (Leukotrienes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 31340R8PVU (dazmegrel)
RN  - 54397-85-2 (Thromboxane B2)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 58962-34-8 (6-Ketoprostaglandin F1 alpha)
RN  - 7BO8G1BYQU (Masoprocol)
RN  - EC 1.13.11.12 (Lipoxygenase)
RN  - EC 5.3.99.5 (Thromboxane-A Synthase)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - 6-Ketoprostaglandin F1 alpha/blood
MH  - Animals
MH  - Endotoxins/administration & dosage/blood/*toxicity
MH  - Female
MH  - Hemodynamics/drug effects
MH  - Humans
MH  - Hypertension, Pulmonary/*etiology/physiopathology
MH  - Imidazoles/pharmacology
MH  - Leukotriene Antagonists
MH  - Leukotrienes/metabolism/*physiology
MH  - Lipoxygenase/metabolism
MH  - Masoprocol/pharmacology
MH  - Pentoxifylline/pharmacology
MH  - Sepsis/complications/*physiopathology
MH  - Swine
MH  - Thromboxane A2/antagonists & inhibitors/blood/*physiology
MH  - Thromboxane B2/blood
MH  - Thromboxane-A Synthase/antagonists & inhibitors
MH  - Toxemia
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/metabolism/*physiology
EDAT- 1995/09/01 00:00
MHDA- 2001/03/28 10:01
CRDT- 1995/09/01 00:00
PHST- 1995/09/01 00:00 [pubmed]
PHST- 2001/03/28 10:01 [medline]
PHST- 1995/09/01 00:00 [entrez]
AID - S0002-9629(15)35024-2 [pii]
AID - 10.1097/00000441-199531030-00004 [doi]
PST - ppublish
SO  - Am J Med Sci. 1995 Sep;310(3):103-10. doi: 10.1097/00000441-199531030-00004.