1. Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.
- Author
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Santone DJ, Shahani R, Rubin BB, Romaschin AD, and Lindsay TF
- Subjects
- Animals, Blood Pressure, Cromolyn Sodium pharmacology, Disease Models, Animal, Ketotifen pharmacology, Male, Mast Cells drug effects, Mast Cells enzymology, Microscopy, Fluorescence, Rats, Rats, Sprague-Dawley, Shock, Hemorrhagic complications, Shock, Hemorrhagic pathology, Shock, Hemorrhagic physiopathology, Time Factors, Ventricular Dysfunction, Left pathology, Ventricular Dysfunction, Left physiopathology, beta-N-Acetylhexosaminidases blood, Cell Degranulation drug effects, Mast Cells pathology, Myocardial Contraction drug effects, Resuscitation, Shock, Hemorrhagic therapy, Ventricular Dysfunction, Left etiology, Ventricular Function, Left drug effects
- 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.
- Published
- 2008
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