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Mast cell stabilization improves cardiac contractile function following hemorrhagic shock and resuscitation.
- Source :
-
American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2008 Jun; Vol. 294 (6), pp. H2456-64. Date of Electronic Publication: 2008 Apr 04. - Publication Year :
- 2008
-
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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0363-6135
- Volume :
- 294
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Heart and circulatory physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18390822
- Full Text :
- https://doi.org/10.1152/ajpheart.00925.2007