Stress-induced cardiac mast cell (MC) activation and silent ischemia

Stress is known to precipitate or exacerbate atopic diseases associated with MC which secrete numerous vasoactive molecules and cytokines. Moreover, brain MC were recently activated by immobilization stress, a process mediated by corticotropin-releasjng hormone (CRH). In view of the fact that MC are present in the heart, have been associated with coronary atherosclerosis and myocardial infarction (MI), while silent ischemia has been linked to mental stress, we investigated whether immobilization stress may affect cardiac MC. Male Sprague/Dawley rats weighing about 300g each (Taconic, NY) were either kept in their cage (control) or were placed in a Plexiglas immobilizer for 30 min at room temperature (rt). At the end of this period, the animals were anesthetized with a single intraperitoneal (ip) injection of xylazine and ketamine (0.5 ml each of 20 mg/ml), were killed by asphyxiation over CO2 vapor and the heart was rapidly removed and fixed with 4% para formaldehyde for 10 min at rt. Frozen thin sections (7 m) were then stained with acidified toluidine blue (pH<2.5) and examined at 200x. MC activation, judged as granule content extrusion and loss of >20% of cellular staining, was 52±9% (n=4002) in stress , as compared to (p<-05) 26+6% in controls (n=4002). Pretreatment ip with 1 mg/ml of a polyclonal antibody to CRH 60 min prior to stress, reduced (p<.OS) MC activation to 28± 3% (n=6405), while treatment neonatally with capsaicin to deplete sensory nerve fibers of their peptide content did not statistically affect (p>.05) MC activation which was 47±3% (n=3573). Pretreatment ip with 25 mg/kg disodium cromoglycate totally inhibited (p<.05) MC activation to 27±1% (n=7795). Non-traumatic stress clearly activates cardiac MC through CRH, but apparently not through substance P, and could have implications for the pathophysiology and treatment of silen⁺ ischemia and MI (supported by Kos PharmaceuHeals, FL).