Pharmacologic inhibition of mast cell degranulation prevents left ventricular remodeling induced by chronic volume overload in rats.
BACKGROUND
Left ventricular (LV) hypertrophy and dilation are important compensatory responses to chronic volume overload; however, the mechanisms responsible for this LV remodeling have not been well characterized. Previous observations that the number of myocardial mast cells are increased in congestive heart failure (CHF) suggested the hypothesis that mast cells might be involved in the ventricular remodeling induced by a chronic volume overload.


RESULTS
Accordingly, the intent of this study was to determine the contribution of mast cells to LV remodeling, dysfunction, and morbidity/mortality secondary to CHF in the infrarenal aortocaval fistula model of sustained volume overload. To this end, LV end-diastolic pressure, size, and function (ie, isovolumetric pressure-volume relations in the blood-perfused isolated heart) were assessed in both nedocromil sodium treated and untreated rats at 8 weeks after fistula and compared with age-matched controls. Nedocromil, a mast cell-stabilizing drug, effectively prevented the LV dilation and decreased contractility seen in the untreated fistula group in a dose-dependent fashion, resulting in a significant reduction in the incidence of morbidity/mortality from CHF.


CONCLUSIONS
The ability of mast cell stabilization to prevent ventricular dilation induced by chronic volume overload identifies a key role for mast cells in the regulation of myocardial remodeling.
Brower
Gregory L
GL
Department of Anatomy, Physiology and Pharmacology, Auburn University, Auburn, Alabama, USA.
Janicki
Joseph S
JS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D015550:Cell Degranulation / Q000187:drug effects*; D002908:Chronic Disease; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006333:Heart Failure / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017835:Nedocromil / Q000008:administration & dosage; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology; D017725:Ventricular Pressure / Q000187:drug effects / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects*
D000893:Anti-Inflammatory Agents; D017835:Nedocromil