title: Triiodothyronine (T3) supplementation maintains surfactant biochemical integrity during sepsis.
abstract: Surfactant functional effectiveness is dependent on phospholipid compositional integrity: sepsis decreases this through an undefined mechanism. Sepsis-induced hypothyroidism is commensurate and may be related. This study examines the effect of triiodothyronine (T3) supplementation on surfactant function, metabolism, and composition during sepsis. Male Sprague-Dawley rats (n = 75) underwent sham laparotomy or cecal ligation and puncture (CLP) with or without T3 supplementation (CLP/T3; 3 ng/hr). Twenty-four hours later, surfactant was obtained by lavage. Total phospholipids were determined by chromatography. Choline phosphate cytidyltransferase (CT) activity was determined by the formation of cytidine diphosphate (CDP)-choline. In vivo lung compliance was determined by lung inflation; surfactant hysteresis plots were determined on a pulsating bubble surfactometer. Lung compliance and surfactant hysteresis plots were significantly affected by sepsis; T3 modulated this (dynamic compliance: sham = 0.66 +/- 0.02, CLP = 0.47 +/- 0.06, CLP/T3 = 0.56 +/- 0.02 mm Hg/mL; p < 0.05). Sepsis produced a decrease in phosphatidylglycerol, and phosphatidic acid, with an increase in lesser surface active lipids phosphatidylserine and phosphatidylinositol. Hormonal replacement prevented these alterations. Lung CT activity was increased by sepsis independent of T3 treatment. Thyroid hormone may have an active role in lung functional preservation during sepsis caused by maintenance of surfactant biophysical and compositional homeostasis.
authors.affiliation: Department of Surgery, Wayne State University School of Medicine, Detroit, MI, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Dulchavsky
authors.forename: S M
authors.initials: SM
authors.lastname: Ksenzenko
authors.forename: A A
authors.initials: AA
authors.lastname: Saba
authors.forename: L N
authors.initials: LN
authors.lastname: Diebel
mesh_terms: D000818:Animals; D019916:Choline-Phosphate Cytidylyltransferase; D003566:Cytidine Diphosphate Choline / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008170:Lung Compliance; D008297:Male; D009713:Nucleotidyltransferases / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism; D014284:Triiodothyronine / Q000627:therapeutic use*
chemical_list: D010743:Phospholipids; D011663:Pulmonary Surfactants; D014284:Triiodothyronine; D003566:Cytidine Diphosphate Choline; D009713:Nucleotidyltransferases; D019916:Choline-Phosphate Cytidylyltransferase