Abstract
We investigated the role of leukotrienes and cyclooxygenase products in endotoxin-induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (RL), arterial P(O2), leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto-PgF(1α) and PgF(2α) were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 μg/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 441 and 353% of baseline, respectively, during the early phase (0 to 1 h), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with mild hypoxemia, marked leukopenia, and marked increases in plasma TxB2, 6-keto-PgF(1α) and PgF(2α). The FPL-57231 completely blocked the endotoxin-induced changed in PVR, RL, and Pa(O2) during both phases without preventing the increases in TxB2; however, it partly attenuated the increases in 6-keto-PgF(1α) and enhanced the generation of PgF(2α). Indomethacin, which blocked the endotoxin-induced increases in TxB2, 6-keto-PgF(1α) PgF(2α), and RL, only partly blocked the increase in PVR during the early phase, followed by an exaggerated increase in PVR during the late phase. Both FPL-57231 and indomethacin failed to prevent the endotoxin-induced decrease in WBC count. In another group of 5 sheep, a 10-min infusion of FPL-57231, 4 h after endotoxin, reversed the Phase II increase in PVR. These data indicate that leukotrienes may play an important role in endotoxin-induced changes in pulmonary hemodynamics and airway mechanics. The increase in RL and initial changes in PVR may be mediated by leukotrienes and cyclooxygenase products, whereas the subsequent changes in PVR appear to be predominantly mediated by leukotrienes.
| Original language | English |
|---|---|
| Pages (from-to) | 1149-1157 |
| Number of pages | 9 |
| Journal | American Review of Respiratory Disease |
| Volume | 134 |
| Issue number | 6 |
| State | Published - Dec 1 1986 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine
Cite this
Endotoxin-induced changes in pulmonary hemodynamics and respiratory mechanics : Role of lipoxygenase and cyclooxygenase products. / Ahmed, T.; Wasserman, M. A.; Muccitelli, R.; Tucker, S.; Gazeroglu, H.; Marchette, B.
In: American Review of Respiratory Disease, Vol. 134, No. 6, 01.12.1986, p. 1149-1157.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Endotoxin-induced changes in pulmonary hemodynamics and respiratory mechanics
T2 - Role of lipoxygenase and cyclooxygenase products
AU - Ahmed, T.
AU - Wasserman, M. A.
AU - Muccitelli, R.
AU - Tucker, S.
AU - Gazeroglu, H.
AU - Marchette, B.
PY - 1986/12/1
Y1 - 1986/12/1
N2 - We investigated the role of leukotrienes and cyclooxygenase products in endotoxin-induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (RL), arterial P(O2), leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto-PgF(1α) and PgF(2α) were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 μg/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 441 and 353% of baseline, respectively, during the early phase (0 to 1 h), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with mild hypoxemia, marked leukopenia, and marked increases in plasma TxB2, 6-keto-PgF(1α) and PgF(2α). The FPL-57231 completely blocked the endotoxin-induced changed in PVR, RL, and Pa(O2) during both phases without preventing the increases in TxB2; however, it partly attenuated the increases in 6-keto-PgF(1α) and enhanced the generation of PgF(2α). Indomethacin, which blocked the endotoxin-induced increases in TxB2, 6-keto-PgF(1α) PgF(2α), and RL, only partly blocked the increase in PVR during the early phase, followed by an exaggerated increase in PVR during the late phase. Both FPL-57231 and indomethacin failed to prevent the endotoxin-induced decrease in WBC count. In another group of 5 sheep, a 10-min infusion of FPL-57231, 4 h after endotoxin, reversed the Phase II increase in PVR. These data indicate that leukotrienes may play an important role in endotoxin-induced changes in pulmonary hemodynamics and airway mechanics. The increase in RL and initial changes in PVR may be mediated by leukotrienes and cyclooxygenase products, whereas the subsequent changes in PVR appear to be predominantly mediated by leukotrienes.
AB - We investigated the role of leukotrienes and cyclooxygenase products in endotoxin-induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (RL), arterial P(O2), leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto-PgF(1α) and PgF(2α) were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 μg/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 441 and 353% of baseline, respectively, during the early phase (0 to 1 h), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with mild hypoxemia, marked leukopenia, and marked increases in plasma TxB2, 6-keto-PgF(1α) and PgF(2α). The FPL-57231 completely blocked the endotoxin-induced changed in PVR, RL, and Pa(O2) during both phases without preventing the increases in TxB2; however, it partly attenuated the increases in 6-keto-PgF(1α) and enhanced the generation of PgF(2α). Indomethacin, which blocked the endotoxin-induced increases in TxB2, 6-keto-PgF(1α) PgF(2α), and RL, only partly blocked the increase in PVR during the early phase, followed by an exaggerated increase in PVR during the late phase. Both FPL-57231 and indomethacin failed to prevent the endotoxin-induced decrease in WBC count. In another group of 5 sheep, a 10-min infusion of FPL-57231, 4 h after endotoxin, reversed the Phase II increase in PVR. These data indicate that leukotrienes may play an important role in endotoxin-induced changes in pulmonary hemodynamics and airway mechanics. The increase in RL and initial changes in PVR may be mediated by leukotrienes and cyclooxygenase products, whereas the subsequent changes in PVR appear to be predominantly mediated by leukotrienes.
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M3 - Article
C2 - 3098146
AN - SCOPUS:0023001552
VL - 134
SP - 1149
EP - 1157
JO - American Journal of Respiratory and Critical Care Medicine
JF - American Journal of Respiratory and Critical Care Medicine
SN - 1073-449X
IS - 6
ER -