Abstract
The sulfidopeptide leukotrienes (LT) have been implicated as important pathophysiological mediators in septic shock. To further define the role of these compounds, we utilized a porcine endotoxicosis model to study the effects of pre- and concurrent treatment with LY203647, a novel LT receptor antagonist. Pentobarbital-anesthetized pigs (13-20 kg) were mechanically ventilated with 100% O2. Superior mesenteric arterial flow (Q̇sma) was measured using an ultrasonic flow probe. Ileal intramucosal hydrogen ion concentration, [H+]1, was estimated tonometrically. Pigs in groups I and II were infused with endotoxin (250 μg/kg) and resuscitated with saline (1.2 ml/kg min). Group I (n = 8) were controls; Group II (n = 8) were pretreated with LY203647 (30 mg/kg bolus, then 10 mg/kg h). Treatment with LY203647 persistently and significantly (P < .05) improved post-LPS pO2 and transiently improved Q̇sma. Treatment with LY203647 did not affect [H+]1. Lung extravascular wet-to-dry weight ratios were 7.13 ± .33 and 5.43 ± .09 in groups I and II, respectively (P < .001). These data suggest that sulfidopeptide LT are important mediators of key pathophysiologic events in this porcine model of endotoxic shock and the adult respiratory distress syndrome (ARDS).
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7-16 |
| Number of pages | 10 |
| Journal | Circulatory Shock |
| Volume | 33 |
| Issue number | 1 |
| State | Published - 1991 |
| Externally published | Yes |
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Keywords
- adult respiratory distress syndrome
- endotoxemia
- leukotrienes
- septic shock
- tonometer
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Beneficial effects of LY203647, a novel leukotriene C4/D4 antagonist, on pulmonary function and mesenteric perfusion in a porcine model of endotoxic shock and ARDS. / Cohn, S. M.; Kruithoff, K. L.; Rothschild, H. R.; Wang, H.; Antonsson, J. B.; Fink, M. P.
In: Circulatory Shock, Vol. 33, No. 1, 1991, p. 7-16.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Beneficial effects of LY203647, a novel leukotriene C4/D4 antagonist, on pulmonary function and mesenteric perfusion in a porcine model of endotoxic shock and ARDS
AU - Cohn, S. M.
AU - Kruithoff, K. L.
AU - Rothschild, H. R.
AU - Wang, H.
AU - Antonsson, J. B.
AU - Fink, M. P.
PY - 1991
Y1 - 1991
N2 - The sulfidopeptide leukotrienes (LT) have been implicated as important pathophysiological mediators in septic shock. To further define the role of these compounds, we utilized a porcine endotoxicosis model to study the effects of pre- and concurrent treatment with LY203647, a novel LT receptor antagonist. Pentobarbital-anesthetized pigs (13-20 kg) were mechanically ventilated with 100% O2. Superior mesenteric arterial flow (Q̇sma) was measured using an ultrasonic flow probe. Ileal intramucosal hydrogen ion concentration, [H+]1, was estimated tonometrically. Pigs in groups I and II were infused with endotoxin (250 μg/kg) and resuscitated with saline (1.2 ml/kg min). Group I (n = 8) were controls; Group II (n = 8) were pretreated with LY203647 (30 mg/kg bolus, then 10 mg/kg h). Treatment with LY203647 persistently and significantly (P < .05) improved post-LPS pO2 and transiently improved Q̇sma. Treatment with LY203647 did not affect [H+]1. Lung extravascular wet-to-dry weight ratios were 7.13 ± .33 and 5.43 ± .09 in groups I and II, respectively (P < .001). These data suggest that sulfidopeptide LT are important mediators of key pathophysiologic events in this porcine model of endotoxic shock and the adult respiratory distress syndrome (ARDS).
AB - The sulfidopeptide leukotrienes (LT) have been implicated as important pathophysiological mediators in septic shock. To further define the role of these compounds, we utilized a porcine endotoxicosis model to study the effects of pre- and concurrent treatment with LY203647, a novel LT receptor antagonist. Pentobarbital-anesthetized pigs (13-20 kg) were mechanically ventilated with 100% O2. Superior mesenteric arterial flow (Q̇sma) was measured using an ultrasonic flow probe. Ileal intramucosal hydrogen ion concentration, [H+]1, was estimated tonometrically. Pigs in groups I and II were infused with endotoxin (250 μg/kg) and resuscitated with saline (1.2 ml/kg min). Group I (n = 8) were controls; Group II (n = 8) were pretreated with LY203647 (30 mg/kg bolus, then 10 mg/kg h). Treatment with LY203647 persistently and significantly (P < .05) improved post-LPS pO2 and transiently improved Q̇sma. Treatment with LY203647 did not affect [H+]1. Lung extravascular wet-to-dry weight ratios were 7.13 ± .33 and 5.43 ± .09 in groups I and II, respectively (P < .001). These data suggest that sulfidopeptide LT are important mediators of key pathophysiologic events in this porcine model of endotoxic shock and the adult respiratory distress syndrome (ARDS).
KW - adult respiratory distress syndrome
KW - endotoxemia
KW - leukotrienes
KW - septic shock
KW - tonometer
UR - http://www.scopus.com/inward/record.url?scp=0026057358&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0026057358&partnerID=8YFLogxK
M3 - Article
C2 - 2009603
AN - SCOPUS:0026057358
VL - 33
SP - 7
EP - 16
JO - Journal of inflammation
JF - Journal of inflammation
SN - 1078-7852
IS - 1
ER -