An Animal Model Of Plaque Rupture And Thrombosis Induced By Wind Chill Based On The Theory Of "external Wind Provokes Internal Wind"

BACKGROUND:Environmental factors are one of the common precipitating factors of acute coronary syndrome(ACS).Dr.Wang observed that the number of patients admitted to hospital with ACS increased significantly during windy and cold weather,and linked this phenomenon to the theory of "exogenous wind inducing endogenous wind".Atherosclerotic plaque rupture and atherothrombosis are the major mechanisms of ACS.Based on the theory of "exogenous wind inducing endogenous wind",we speculate that exogenous wind,represented by wind chill,may cause plaque rupture and subsequent thrombosis in the event of "endogenous collateral-wind".OBJECTIVE:To explore the effects of wind,cold and wind-chill stimuli on the risk of plaque rupture and atherothrombosis in vulnerable plaque models;to find an appropriate wind-chill stimulation conditions,so as to develop an animal model of cardiovascular disease with "exogenous wind inducing endogenous wind" and observe the changes of the evidence in TCM.METHODS:We performed a tandem stenosis(TS)operation on ApoE-/-mice which feeding with high-fat feed,to develop a vulnerable plaque model.11 weeks after surgery,all the animals were randomly divided into 7 groups:control group,cold-only,wind only,wind chill 6 h,wind chill 8 h,wind chill 10 h,and wind chill 18 h.After giving them the corresponding weather conditions by an artificial climate chamber,animals were sacrificed and the target arteries was taken to compare between the groups mainly in the pathological morphological ways:the incidence of rupture of fibrous cap,intraplaque hemorrhage,and luminal thrombosis are the major endpoint events.And we assessed the area of the plaque,the degree of vascular luminal stenosis,and the content of each component(lipids,smooth muscle cells,and macrophages)in each group as the baseline characteristics,to help verifying whether acute wind-chill stimulation would increase the event of plaque rupture and atherothrombosis.We also observed the ordinary condition of mice,and used the Longa score to assess whether they had neurological deficits.Finally,we used the TCM Syndrome Scale to assess the TCM syndrome of mice after being stimulated by those acute weather factors,to further develop the TCM theory of "endogenous collateral-wind".Conclusions:1.The TS model is suitable for studying the effect of environmental factors on plaque rupture and atherothrombosis.2.Acute wind-chill stimulation may cause an increase in plaque rupture;both acute wind and acute wind-chill stimulation may increase the risk of atherothrombosis;none of these stimuli caused neurological deficit symptoms in the TS model mice.3."Exogenous wind" likes the wind-chill may trigger "endogenous collateral-wind" events such as plaque rupture and atherothrombosis,and the animals will show some corresponding TCM syndromes.