IVIG treatment improved myocardial contractile function, restoring longitudinal strain to near normal levels by day 56 in KD mice, with LS negatively correlated to myocarditis severity (r = -0.94, P < 0.001).
Does intravenous immunoglobulin improve myocardial contractile dysfunction in a murine model of Kawasaki disease?
High-resolution speckle-tracking echocardiography can detect early myocardial contractile dysfunction in a Kawasaki disease mouse model, which is shown to be reversible with IVIG treatment.
Effect estimate: LS at day 56: KD + IVIG 19.8% vs KD 17.4%, P < 0.05
Absolute Event Rate: 19.8% vs 20.6%
p-value: p=<0.05 for improvement of LS in IVIG-treated vs untreated KD at days 14 and 28; correlation of LS and myocarditis score: r = -0.94, P < 0.001
Background Myocarditis is a common feature of acute Kawasaki disease (KD) and a major contributor to myocardial contractile dysfunction, which can be alleviated by timely intravenous immunoglobulin (IVIG) treatment. However, the effects of KD on myocardial systolic function and the impact of IVIG on myocardial recovery are not well understood in animal models. This study aims to explore whether left ventricular systolic dysfunction occurs in a KD mouse model and to evaluate the potential benefits of IVIG in mitigating myocardial contractile impairment using high-resolution speckle-tracking imaging (STI). Methods We utilized a Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis to assess the effects of IVIG treatment on myocardial dysfunction. Histological analyses and speckle-tracking strain imaging were performed to evaluate myocardial function during the progression of KD-induced vasculitis and myocarditis. Results IVIG treatment significantly prevented both myocarditis and vasculitis. Conventional echocardiographic analyses showed differences in ejection fraction between the KD and control groups 14 days after LCWE injection, regardless of IVIG treatment. Notably, both the KD and KD + IVIG groups exhibited reduced longitudinal strain (LS) as early as 3 days post-injection compared to the control group. While LS remained decreased in the KD group throughout the disease progression, the KD + IVIG group showed a recovery to normal LS levels by day 56. At 14 and 28 days post-LCWE injection, LS in the KD group was significantly lower than in the KD + IVIG group. LS was negatively related to myocarditis scores (r = −0.94, P 0.001). Conclusions Myocardial contractile dysfunction resulting from myocarditis occurs in the KD mouse model and can be improved with IVIG treatment. High-resolution STI offers a more sensitive and accurate method for assessing myocardial dysfunction and the effects of cardioprotective treatments compared to conventional echocardiography.
Wang et al. (Wed,) conducted a other in Male C57BL/6 mice aged 4 weeks with LCWE-induced Kawasaki disease vasculitis and myocarditis (n=120). Intraperitoneal intravenous immunoglobulin (IVIG) vs. Untreated KD group with LCWE only, and normal control group with PBS was evaluated on Myocardial contractile function assessed by longitudinal strain (LS) via high-resolution speckle-tracking echocardiography and histological myocarditis scores (LS at day 56: KD + IVIG 19.8% vs KD 17.4%, P < 0.05, p=<0.05 for improvement of LS in IVIG-treated vs untreated KD at days 14 and 28; correlation of LS and myocarditis score: r = -0.94, P < 0.001). IVIG treatment improved myocardial contractile function, restoring longitudinal strain to near normal levels by day 56 in KD mice, with LS negatively correlated to myocarditis severity (r = -0.94, P < 0.001).