title: Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.
abstract: Hemorrhagic shock (HS) is associated with cardiac contractile dysfunction. Mast cell (MC) degranulation is hypothesized to mediate the cardiodepressant effect. Cardiac function was assessed after HS and resuscitation (HS/R) with the administration of the MC stabilizers to prevent MC degranulation. Anesthetized male Sprague-Dawley rats were randomized to sham-operated control or HS/R groups and underwent 60 min of HS followed by 2 h of resuscitated reperfusion. Animals in the HS/R groups were randomized to receive cromolyn (5 mg/kg), ketotifen (1 mg/kg), or saline 15 min before shock. Hearts were excised following HS or 2 h of reperfusion, and function was assessed on a Langendorff apparatus. A second group of randomized animals had serial blood samples taken to assess MC degranulation by quantifying levels of serum beta-hexosaminidase. Hearts were excised at 0 min (before HS) and following 60 min of HS (before resuscitation) for a histological evaluation of MC density and degranulation. In vivo MC stabilization using ketotifen and cromolyn improved cardiac peak systolic pressure (P < 0.05), contractility (P < 0.05), and relaxation (P < 0.05) compared with that of HS controls. Serum beta-hexosaminidase increased during HS/R and was inhibited by MC stabilization (P < 0.05). Degranulation was inhibited when assessed by histochemistry and immune fluorescence. The inhibition of MC degranulation can significantly improve cardiac function following HS/R.
authors.affiliation: Division of Vascular Surgery, University Health Network, and the Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
authors.forename: David J
authors.initials: DJ
authors.lastname: Santone
authors.forename: Rohan
authors.initials: R
authors.lastname: Shahani
authors.forename: Barry B
authors.initials: BB
authors.lastname: Rubin
authors.forename: Alex D
authors.initials: AD
authors.lastname: Romaschin
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lindsay
mesh_terms: D000818:Animals; D001794:Blood Pressure; D015550:Cell Degranulation / Q000187:drug effects; D004205:Cromolyn Sodium / Q000494:pharmacology; D004195:Disease Models, Animal; D007665:Ketotifen / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008856:Microscopy, Fluorescence; D009200:Myocardial Contraction / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013997:Time Factors; D018487:Ventricular Dysfunction, Left / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects; D001619:beta-N-Acetylhexosaminidases / Q000097:blood
chemical_list: D001619:beta-N-Acetylhexosaminidases; D004205:Cromolyn Sodium; D007665:Ketotifen