Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.
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.
Santone
David J
DJ
Division of Vascular Surgery, University Health Network, and the Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Shahani
Rohan
R
Rubin
Barry B
BB
Romaschin
Alex D
AD
Lindsay
Thomas F
TF
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
D001619:beta-N-Acetylhexosaminidases; D004205:Cromolyn Sodium; D007665:Ketotifen