DIETARY LIPIDS &THE PULMONARY VASCULATURE DURING STRESS

  • Murray, Michael J, (PI)

Project: Research project

Description

The content and nature of dietary polyunsaturated fat can have
important effects upon cell function and upon systems as diverse as
the vasculature or those mediating immunity. Polyunsaturated lipids
of the n-3 type and certain n-6 fatty acids may protect against, or
alter the occurrence of, diseases such as coronary atherosclerosis
and arthritis. Altered eicosanoid (prostaglandins and thromboxanes)
formation may underlie these potentially beneficial effects.
However, in addition to an action upon blood vessels and joints,
preliminary data from this and other laboratories indicate that the
dietary n-3 fatty acids can directly improve the course and outcome
of septic shock. Such effects are particularly important as septic
shock is not only difficult to treat and often afflicts young people,
but in addition has a devastating mortality rate that may be as high
as 50%. Even small improvements in management may have important
effect on survival. Currently available nutrition products used to
support such patients contain little n-3 fatty acids, but have
substantial amounts of potentially harmful n-6 fats. Certain n-6
fats may not only fail to offer protection, but may have deleterious
effects on vascular tone and tissue perfusion. Preliminary data
suggests altered vascular responsiveness as the causative factor.
Our purpose is to define in a porcine model the effects of n-3 fatty
acids on the physiologic and eicosanoid response to sepsis.
Specifically, these studies will determine: (1) whether platelets and
endothelial cells release of eicosanoids is influenced by incubation
with specific n-6 and n-3 fatty acids, and whether release of these
eicosanoids is affected by extracellular fatty acids without the
acids necessarily incorporated into the membrane phospholipids of
these cells. (2) Whether these same dietary fatty acids influence
release of eicosanoids from, and contractility of, pulmonary arteries
in vitro. (3) Whether modification of dietary lipid affects platelet
function after i.v. administration of low-dose endotoxin. (4)
Whether addition of n-3 fatty acids or gamma-linolenic acid to the
diet influences the in vitro interaction between platelets and
arterial endothelium. To the extent that the pathophysiologic and eicosanoid response to
sepsis is altered, these experiments will clarify the role of dietary
18 and 20 carbon chain fatty acids in the pulmonary vascular response
to a stress such as sepsis.
StatusFinished
Effective start/end date2/1/921/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Eicosanoids
Omega-3 Fatty Acids
Blood Vessels
Lipids
Lung
Fatty Acids
Sepsis
Blood Platelets
gamma-Linolenic Acid
Diet Therapy
Septic Shock
Dietary Fats
Thromboxanes
Endotoxins
Arthritis
Prostaglandins
Endothelium
Fats
Immunity
Phospholipids

ASJC

  • Medicine(all)