title: Pretreatment with FK506 improves survival rate and gas exchange in canine model of acute lung injury.
abstract: The novel effects of FK506 on shock induced by lipopolysaccharide and phorbol myristate acetate (LPS/PMA) were studied using beagles. Five groups were studied: endotoxin shock control group (both 0.5 mg/kg of LPS and 30 microg/kg of PMA, n = 6); methylprednisolone-treated endotoxin shock group (n = 5); FK506-treated endotoxin shock groups in which intravenous infusions of FK506 at 2.5 microg/kg/h (low dose, n = 5), 8 microg/kg/h (medium dose, n = 5), and 25 microg/kg/h (high dose, n = 5) were administered. In the control group, the survival rate was 33%. Also, arterial hypoxemia, systemic hypotension, and marked increases in pulmonary vascular resistance (PVR) and wet-to-dry weight ratio (W/D) were observed. FK506 treatment at both medium and high doses significantly attenuated these LPS/PMA-induced physiological changes, and the survival rates were 80 and 100%, respectively. On the other hand, in the methylprednisolone group, no obvious effects were observed. The present study suggests that FK506 could have prophylactic potential against acute lung injury in endotoxin shock.
authors.affiliation: Medicinal Biology Research Laboratories, Fujisawa Pharmaceutical Company, Osaka, and Department of Medicine, School of Medicine, Keio University, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koshika
authors.forename: A
authors.initials: A
authors.lastname: Ishizaka
authors.forename: I
authors.initials: I
authors.lastname: Nagatomi
authors.forename: Y
authors.initials: Y
authors.lastname: Sudo
authors.forename: N
authors.initials: N
authors.lastname: Hasegawa
authors.forename: T
authors.initials: T
authors.lastname: Goto
mesh_terms: D000818:Animals; D004285:Dogs; D006439:Hemodynamics; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D009929:Organ Size; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000401:mortality* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D012772:Shock, Septic / Q000150:complications / Q000401:mortality* / Q000503:physiopathology / Q000517:prevention & control*; D015996:Survival Rate; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus