Kanjo Yamamoto

Mast Cells Play a Critical Role in the Pathogenesis of Viral Myocarditis

Background— Mast cells are powerful producers of multiple cytokines and chemical mediators playing a pivotal role in the pathogenesis of various cardiovascular diseases. We examined the role of mast cells in murine models of heart failure due to viral myocarditis, using 2 strains of mast cell–deficient mice. Methods and Results— Two strains of mast cell–deficient mice, WBB6F1-KitW/KitW-v (W/WV) and WCB6F1-KitlSl/KitlSl-d (Sl/Sld), were inoculated with 10 plaque-forming units of the encephalomyocarditis virus intraperitoneally. On day 14 after inoculation, survival of W/WV mice was significantly higher than that of their control littermates (77% versus 31%; P=0.03; n=13). On histological examination on day 7, myocardial necrosis and cellular infiltration were significantly less pronounced in W/WV and Sl/Sld mice than in their control littermates (area of infiltration, 7.6±3.5% versus 29.3±15.6%; P=0.002; area of necrosis, 7.6±3.5% versus 30.0±17.2%; P=0.003; n=10). Histological examination showed more severe changes in mast cell–reconstituted than in –nonreconstituted W/WV and Sl/Sld mice. The gene expressions of mast cell proteases were upregulated in the acute phase of viral myocarditis and rose further in the subacute phase of heart failure. Their activation coincided with the development of myocardial necrosis and fibrosis and correlated with the upregulation of gene expression of matrix metalloproteinase-9. The histamine H1-receptor antagonist bepotastine improved encephalomyocarditis viral myocarditis. Conclusions— These observations suggest that mast cells participate in the acute inflammatory reaction and the onset of ventricular remodeling associated with acute viral myocarditis and that the inhibition of their function may be therapeutic in this disease.

Suppression of cytokines and nitric oxide production, and protection against lethal endotoxemia and viral myocarditis by a new NF-κB inhibitor

Nuclear factor kappa B (NF‐κB) is activated by several factors, which increase the inflammatory response, and this activation, in turn, leads to the expression of several genes such as cytokines, and may play an important role in cardiovascular diseases.

The impact of lesion length and vessel size on outcomes after sirolimus-eluting stent implantation for in-stent restenosis

Objectives: We evaluated the predictors of recurrent restenosis and the impact of lesion length and vessel size on outcomes in patients treated with routine sirolimus-eluting stent (SES) implantation for in-stent restenosis (ISR) of bare-metal stent (BMS). Methods: In this study, 250 consecutive patients with 275 lesions after SES implantation for ISR of BMS were enrolled. Follow-up angiogram was obtained in 239 patients with 258 lesions eight months after implantation (follow-up rate: 95.6%). We compared characteristics of patients and lesions between the two groups (the recurrent restenosis group and the no-restenosis group). Results: Recurrent restenosis was angiographically documented in 43 lesions (16.7%). Recurrent restenosis was found in 30.4% with small vessel lesions (reference diameter of less than 2.5 mm, 92 lesions) and 23% with the diffuse type lesions (106 lesions). Seventy-two per cent of patients had a focal pattern of recurrent restenosis. Previously recurrent ISR lesions (odds ratio (OR) 1.94, 95% confidence interval (CI) 0.94 to 4.06, p = 0.05), reference diameter of less than 2.5 mm (OR 2.41, CI 1.05 to 5.41, p = 0.03), diffuse type restenosis (OR 4.48, CI 2.12 to 9.94, p = 0.0001) and dialysis patients (OR 4.72, CI 1.42 to 15.7, p = 0.01) were independent predictors of recurrent restenosis. Conclusions: Small vessels, diffuse type restenosis and dialysis patients were still the predictors of recurrent restenosis in patients treated with SES for ISR of BMS.

Cetirizine a histamine H1 receptor antagonist improves viral myocarditis

BackgroundWe showed that mast cells played a critical role in the progression of heart failure induced by pressure overload and viral myocarditis in mice. In this study, we investigated the effect of cetirizine, a selective H1 receptor antagonist, on experimental viral myocarditis induced by encephalomyocarditis (EMC) virus.MethodsFour-week-old inbred male DBA/2 mice were inoculated intraperitoneally with 10 plaque-forming units (pfu) of the EMC virus. Cetirizine was administered orally at a dose of 1 or 10 mg/kg per day for the survival study, and 1 mg/kg for the histologic and gene expression studies, beginning on the day of viral inoculation.ResultsCetirizine improved survival dose dependently. Heart weight to body weight ratio was significantly decreased in mice treated with cetirizine. The area of myocardial necrosis was significantly smaller in the hearts of mice treated with cetirizine compared with controls. Gene expressions of tumor necrosis factor, interleukin 6, and metalloproteinase 2 were significantly suppressed in the hearts of mice treated with cetirizine.ConclusionThese results suggest that cetirizine exerts its beneficial effects on viral myocarditis by suppressing expression of pro-inflammatory cytokines, genes related to cardiac remodeling in the hearts of mice.