Background: Mouse echocardiography is an established, non-invasive method to evaluate experimental cardiovascular disease. The murine Kawasaki disease (KD) model demonstrates aortic and coronary artery inflammation by histology. The clinical relevance of these pathological changes has not been confirmed. In children, KD involves coronary artery abnormalities visualized by echocardiography. However, echocardiography has not been previously applied to the mouse KD model. We hypothesized that coronary vasculitis caused the lactobacillus casei cell wall extract (LCE) causes abnormalities detectable by echo.
Methods: Male mice (ages 3-4 months) were injected with LCE or vehicle. Sedated echos were performed with a VisualSonics Vevo 2100 system. Twelve mice (8 LCE and 4 vehicle) had pre-injection echos followed by serial studies for 6-10 weeks. Evaluations were blinded to treatment group. 2-D measurements were taken at consistent locations in the arteries. Aortic regurgitation was rated based upon clinical criteria. Histology was evaluated at 6 weeks post-LCE.
Results: Mild aortic regurgitation (AR) was present in 6 of 8 mice injected with LCE starting at 1 week post-injection. No AR was present at baseline or vehicle injected mice. LCE mice showed increased aortic root diameter at 6 weeks compared to baseline (1.78mm±0.01 vs 1.52±0.02, p<0.05). Overall left coronary artery dimensions were not changed from baseline at 6 weeks post-LCE, but coronary imaging was difficult. One mouse had a diffusely enlarged left coronary system and severely diminished left ventricular function at 10 weeks post-LCE. Histology findings were present in all LCE-injected mice including aortic valvulitis, myointimal proliferation and a single case of infarction.
Conclusion: The most prominent echo findings in the mouse KD model are severe aortitis with dilation and valvular regurgitation. These features could serve as non-invasive experimental measurements. Coronary dilation was a rare finding; however the coronaries are difficult to evaluate in mice. Overall, the mouse KD model demonstrates greater aortic pathology than found in human KD. Further studies are underway to evaluate additional non-invasive measurements such as vascular strain.