Background: Tachycardia induced cardiomyopathy (TIC) is a relatively rare etiology of reversible dilated cardiomyopathy. The mechanisms involved in TIC remain largely unknown. Among the potential mechanisms of TIC, inflammation has also been suggested. We focused on macrophage activation in a rat model of TIC.
Methods: Chronic tachycardia was induced by long term β-adrenoreceptor activation via administration of low dose isoprenaline in wistar rats (0.1mg/kg/daily, n=10 vs saline n=6). Echocardiography was performed at one and four months, after which animals were sacrificed. To further validate the presence of cardiomyopathy the expression of cardiac calcium handling proteins was evaluated by RT-PCR. Screening of various inflammatory cytokines in sera was evaluated by ELISA. Based on this screening, we subsequently assessed the expression of CD-11b in harvested splenocytes using flow cytometry. In addition, myocardial tissue was obtained and collagen content as well as CD68+ macrophage occurrence was assessed by immunohistology.
Results: Isoprenaline induced a significant tachycardia and after four month echocardiography revealed a decrease in the ejection fraction as well as in the fractional shortening. Upon euthanasia, body weight (441±16 vs 380±15 gr, p<0.005) and heart weight (142±6 vs 175±13 mg, p<0.005) were increased in TIC animals compared to controls. The mRNA expression of SERCA and Phospholamban were significantly reduced (29% and 38% reduction, respectively, P<0.05). No change in RyR2 expression was noted. Serum levels of IL-1 alpha, IL-2 and interferon-gamma. Yet, no significant changes were noticed in the levels of IL-10, IL-13, IL-1 beta, IL-4 and MCP-1. Flow cytometry revealed an elevated number of CD11/b+ splenocytes in TIC rats (P<0.05). Eventually, while no fibrosis was present in TIC-rat myocardial tissue, an elevated CD68+ macrophage occurrence was detected (4.68 fold of control, p<0.005).
Conclusions: Increased macrophage inflammatory activity is present during tachycardia induced cardiomyopathy. Further investigation will be needed to evaluate inflammation role in the underlying pathophysiology of TIC.
