| Backgrounds and ObjectivesOur previous studies have found that the development of left ventricular(LV) dysfunction in spontaneously hypertensive rats(SHR) is related to the abnormal multi-dimensional myocardial deformation and the characteristics of myocardial fibrosis. In this study, we investigate the distribution of myocardial collagen in different layers and remodeling of intramyocardial small arteries in SHRs of LV diastolic dysfunction(DD) and systolic dysfunction(SD), and its relationships with multi-dimensional myocardial strain and global cardiac function, to probe the mechanical mechanism and morphological basis of different types of cardiac dysfunction. Methods83 SHRs and 47 WKY rats were purchased and fed from 12 wks old. Study was performed at the time period of 14-22, 28, 45-66 and 84-102 wks. According to LV function measurements, the rats were divided into 3 groups: Group A( normal group, n=13), group B(DD group, LVEF?70% with increased LVEDP, n=26) and group C(SD group, LVEF<70%, n=17). Echocardiographic measurements included left atrial diameter(LAD) and LV diameter(LVIDd), LV wall thickness, and LVEF; 2D strain included LV longitudinal, radial and circumferential strain(SL, SR and SC respectively). Histological parameters included collagen volume fraction(CVF) from each layer of myocardium, perivascular collagen volume area(PVCA), and the percentage of vessel wall area of intramyocardial small arteries(%WA). Results1. LAD increased(p<0.05) but LVIDd and LVEF were not changed significantly in group B(compared with group A), all LAD, LVIDd and LVMI in group C were significantly higher than group A and B(p<0.05),LVEF decreased[C:(55.75±12.93)% vs A:(78.51±3.46)%, p<0.05].2. In group B, Only decreased SL was found[B:(-11.25±1.51)% vs A:(-14.94±3.13, p<0.05], while all SL, SR and SC were reduced in group C: SL [C:(-6.57±1.59)% vs B:(-11.25±1.51)%, p<0.05]; SR [C:(15.18±5.92)% vs B:(46.44±10.43)%, p<0.05];SC [C:(-8±2.29)% vs B:(-14.96±1.87)%, p<0.05].3. Compared with the group A, CVF in subendocardial and mid-myocardium increased significantly in group B and group C, with the highest in group C(all p<0.05), and subepicardial CVF increased only in group C(all p<0.05); and significantly increased PVCA and %WA were also occurred only in group C(p<0.05).4. All directions of LV strain show negative correlation with CVF, where SC and SR correlated to mid and subepicardial CVF(r=-0.73~-0.83, all p<0.01); LVEF related to All strain measurements with the stronger correlation with SR and SC(r=-0.81,-0.78, all p<0.01).5. Invasive LVEDP in SHR of 28 wks old was lower than that in 14-22wks(p<0.05), increased significantly in 45 wks and later(p<0.05), and higher than WKY of the same age(p<0.05). LV+dp/dt significantly decreased in the 45 wk and later, especially in the time period of 84-102 wk. Conclusions 1. In the development of cardiac dysfunction in SHRs, myocardial collagen deposition occurred firstly in subendocardial myocardium with decreased SL in the stage of DD, while SR, SC and global pump function were preserved; and transmural collagen deposition and the wall thickening of intramyocardial small arteries happened in the stage of SD, with multi-dimensional deformation impaired and LVEF depressed. 2. The progression of LV dysfunction in SHR is related to impaired multi-dimensional deformation, where early subendocardial collagen deposition results in decreased SL and diastolic dysfunction, while transmural collagen deposition and remodeling of small artery and involved all direction's deformations leads to depressed LVEF, suggesting SR and SC being the determinants of LV systolic dysfunction. |
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