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Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep.
J Appl Physiol (1985). 1988 Apr; 64(4):1700-8.JA

Abstract

Leukotrienes have been suggested to play a role in the endotoxin-induced changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is necessary for contraction of airway and vascular smooth muscle as well as for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered whether the calcium antagonist verapamil would modify the endotoxin-mediated pulmonary effects as well as the generation of circulating eicosanoids. In twelve conscious sheep, measurements of pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at predetermined intervals after a 10-min infusion of Escherichia coli endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or 20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 326 and 276% of base line during phase I (0-1 h) and lesser increases to 177 and 157% of base line during phase II (1.5-4 h), respectively (P less than 0.05). SVR also showed biphasic increases of 44 and 42% during phase I and II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(

ABSTRACT

TRUNCATED AT 250 WORDS)

Authors+Show Affiliations

Division of Pulmonary Disease, University of Miami School of Medicine, Mount Sinai Medical Center, Florida 33140.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

3163996

Citation

Ahmed, T, et al. "Effect of Verapamil On Pulmonary and Eicosanoid Responses to Endotoxin in Awake Sheep." Journal of Applied Physiology (Bethesda, Md. : 1985), vol. 64, no. 4, 1988, pp. 1700-8.
Ahmed T, D'Brot J, Wasserman M, et al. Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep. J Appl Physiol (1985). 1988;64(4):1700-8.
Ahmed, T., D'Brot, J., Wasserman, M., Muccitelli, R., Robinson, M., Tucker, S., & Marchette, B. (1988). Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep. Journal of Applied Physiology (Bethesda, Md. : 1985), 64(4), 1700-8.
Ahmed T, et al. Effect of Verapamil On Pulmonary and Eicosanoid Responses to Endotoxin in Awake Sheep. J Appl Physiol (1985). 1988;64(4):1700-8. PubMed PMID: 3163996.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of verapamil on pulmonary and eicosanoid responses to endotoxin in awake sheep. AU - Ahmed,T, AU - D'Brot,J, AU - Wasserman,M, AU - Muccitelli,R, AU - Robinson,M, AU - Tucker,S, AU - Marchette,B, PY - 1988/4/1/pubmed PY - 1988/4/1/medline PY - 1988/4/1/entrez SP - 1700 EP - 8 JF - Journal of applied physiology (Bethesda, Md. : 1985) JO - J Appl Physiol (1985) VL - 64 IS - 4 N2 - Leukotrienes have been suggested to play a role in the endotoxin-induced changes of the pulmonary hemodynamics and airway mechanics. Since Ca2+ is necessary for contraction of airway and vascular smooth muscle as well as for activation of phospholipase A2 and 5-lipoxygenase enzymes, we wondered whether the calcium antagonist verapamil would modify the endotoxin-mediated pulmonary effects as well as the generation of circulating eicosanoids. In twelve conscious sheep, measurements of pulmonary vascular resistance (PVR), systemic vascular resistance (SVR), lung resistance (RL), arterial PO2 (PaO2), leukocyte (WBC) count, arterial thromboxane B2 (TxB2), prostaglandin (PG) F2 alpha, and 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) concentrations were obtained before and at predetermined intervals after a 10-min infusion of Escherichia coli endotoxin (0.3 microgram/kg). On separate occasions, the sheep received a bolus injection of verapamil (150 micrograms/kg) before endotoxin, followed by a continuous infusion of verapamil [10 micrograms.kg-1.min-1 (n = 5) or 20 micrograms.kg-1.min-1 (n = 7)] for up to 4 h post-endotoxin. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 326 and 276% of base line during phase I (0-1 h) and lesser increases to 177 and 157% of base line during phase II (1.5-4 h), respectively (P less than 0.05). SVR also showed biphasic increases of 44 and 42% during phase I and II, respectively. Mean PaO2 decreased by 16 Torr and WBC count decreased from 6.4 +/- 1.5 to 3.3 +/- 1.1 thousand/mm3, associated with marked increases in plasma TxB2, PGF2 alpha, and 6-keto-PGF1 alpha.(ABSTRACT TRUNCATED AT 250 WORDS) SN - 8750-7587 UR - https://www.unboundmedicine.com/medline/citation/3163996/Effect_of_verapamil_on_pulmonary_and_eicosanoid_responses_to_endotoxin_in_awake_sheep_ L2 - https://journals.physiology.org/doi/10.1152/jappl.1988.64.4.1700?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -