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Abstract
Positive end-expiratory pressure (PEEP) leads to a fall in both mean arterial blood
pressure (MAP) and cardiac output (CO). This study tests the hypothesis that humoral
factors, particularly prostanoids, are important mediators of these events. A support
dog was used for ex vivo perfusion of an isolated left lung lobe (LLL) at a fixed
flow. In group I (n = 10) an isolated, isovolumetrically contracting dog heart was
placed in circuit between the support dog and LLL. Indomethacin (5 mg/kg) was used
to pretreat the support dogs and LLL donors of group II (n = 9); support dogs of group
III (n = 5); and LLL donors of group IV (n = 4). This cyclooxygenase inhibitor was
not used for groups I or V (n = 14). The last two groups were similar except that
a heart was not included in the circuit of group V. In group V lobe perfusion during
simple inspiratory mechanical ventilation led to decreases in support dog MAP from
141 ± 3 to 118 ± 15 mm Hg (P < 0.01) and CO from 4.0 ± 0.9 to 2.8 ± 0.8 L/mim (P <
0.01). Application of PEEP further reduced MAP and CO (P < 0.01). In the perfused
isolated hearts of group I, Starling curves were shifted downward during PEEP at five
of six left ventricular balloon volumes tested. In groups II and III MAP and CO were
unchanged with mechanical ventilation or PEEP and were higher than groups I or V (P
< 0.05). Radioimmunoassay of the stable degradation products of prostacyclin and thromboxane
(Tx) A2 demonstrated low concentrations of these prostanoids in support dogs of group III
as compared with group V (P < 0.05). Blocking the LLL donor dog (group IV) produced
hemodynamic results and prostanoid concentrations intermediate between groups I and
V. The results show that mechanical ventilation and PEEP can cause a circulating agent
(s) to be released that results in a decline in MAP and CO. This is prevented with
indomethacin.
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Article info
Publication history
Accepted:
February 10,
1982
Footnotes
☆Supported in part by the National Institute of Health grants GM24891-04 and HL16714-06, the U.S. Army Medical Research and Development Command contract DAMD17-78-C-8026, the Brigham Surgical Group, Inc., and the Trauma Research Foundation.
Identification
Copyright
© 1982 Published by Elsevier Inc.
