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. 1991

S M Cohn, and K L Kruithoff, and H R Rothschild, and H L Wang, and J B Antonsson, and M P Fink
Department of Surgery, University of Massachusetts Medical Center, Worcester 01655.

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 (Qsma) 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 micrograms/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 less than .05) improved post-LPS pO2 and transiently improved Qsma. 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 less than .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).

UI MeSH Term Description Entries
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D012128 Respiratory Distress Syndrome A syndrome characterized by progressive life-threatening RESPIRATORY INSUFFICIENCY in the absence of known LUNG DISEASES, usually following a systemic insult such as surgery or major TRAUMA. ARDS, Human,Acute Respiratory Distress Syndrome,Adult Respiratory Distress Syndrome,Pediatric Respiratory Distress Syndrome,Respiratory Distress Syndrome, Acute,Respiratory Distress Syndrome, Adult,Respiratory Distress Syndrome, Pediatric,Shock Lung,Distress Syndrome, Respiratory,Distress Syndromes, Respiratory,Human ARDS,Lung, Shock,Respiratory Distress Syndromes,Syndrome, Respiratory Distress
D000098 Acetophenones Derivatives of the simplest aromatic ketone acetophenone (of general formula C6H5C(O)CH3).
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012772 Shock, Septic Sepsis associated with HYPOTENSION or hypoperfusion despite adequate fluid resuscitation. Perfusion abnormalities may include but are not limited to LACTIC ACIDOSIS; OLIGURIA; or acute alteration in mental status. Endotoxin Shock,Septic Shock,Shock, Endotoxic,Shock, Toxic,Toxic Shock,Toxic Shock Syndrome,Endotoxin Shocks,Shock Syndrome, Toxic,Shock, Endotoxin,Shocks, Endotoxin,Toxic Shock Syndromes
D013152 Splanchnic Circulation The circulation of blood through the BLOOD VESSELS supplying the abdominal VISCERA. Mesenteric Circulation,Circulation, Mesenteric,Circulation, Splanchnic,Circulations, Mesenteric,Circulations, Splanchnic,Mesenteric Circulations,Splanchnic Circulations
D013189 SRS-A A group of LEUKOTRIENES; (LTC4; LTD4; and LTE4) that is the major mediator of BRONCHOCONSTRICTION; HYPERSENSITIVITY; and other allergic reactions. Earlier studies described a "slow-reacting substance of ANAPHYLAXIS" released from lung by cobra venom or after anaphylactic shock. The relationship between SRS-A leukotrienes was established by UV which showed the presence of the conjugated triene. (From Merck Index, 11th ed) Slow Reacting Substance of Anaphylaxis
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog

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