Association of hypercholesterolemia and cardiac function evaluated by speckle tracking echocardiography in a rabbit model

  • Liyun Liu1,

    Affiliated with

    • Yuming Mu1Email author,

      Affiliated with

      • Wei Han1 and

        Affiliated with

        • Chunmei Wang1

          Affiliated with

          Lipids in Health and Disease201413:128

          DOI: 10.1186/1476-511X-13-128

          Received: 4 March 2014

          Accepted: 1 August 2014

          Published: 9 August 2014

          Abstract

          Background

          Although hypercholesterolemia is a major risk factor for coronary artery disease (CAD), only limited data are available regarding its direct effect on myocardial function apart from CAD. The aim of this study was to evaluate LV systolic function using speckle-tracking echocardiography and investigate the relationship between hypercholesterolemia and myocardial function.

          Methods

          Twenty-eight rabbits were randomly divided into three groups: 8 were fed normal chow for 3 months (group 1) and the remaining 20 were fed an atherogenic diet for 2 (group 2) or 3 months (group 3). Global systolic radial, circumferential and longitudinal peak strain were calculated. Serum total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and myocardial cholesterol levels were measured.

          Results

          Global systolic longitudinal strain were both decreased in the group 2 and 3 (P < 0.001), whereas radial strain were increased (P < 0.001) compared with group 1. Global circumferential strain in the group 3 was significantly reduced (P < 0.001). Serum and myocardial cholesterol concentration markedly increased in the group 2 and group 3 (P < 0.001). There was a significant inverse correlation between longitudinal strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.723, r = - 0.794, r = - 0.700, P both < 0.001). A significant negative correlation was also noted between circumferential strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = - 0.518, P = 0.007; r = - 0.691, P < 0.001; r = - 0.659, P < 0.001). A significant positive correlation was found between radial strain and serum TC, LDL-C as well as myocardial cholesterol levels (r = 0.432, P = 0.028; r = 0.602, P = 0.001; r = 0.469, P = 0.016).

          Conclusion

          Although LV morphology and ejection fractions were not different among the three groups, elevated concentration of cholesterol, especially in serum LDL-C, was significantly associated with LV systolic dysfunction. The findings also indicate that reductions in longitudinal was the first appeared, followed by circumferential, and was compensated for by increasing radial strain.

          Keywords

          Hypercholesterolemia Myocardial function Speckle tracking echocardiography

          Background

          Although hypercholesterolemia has emerged as a strong risk factor for coronary artery disease (CAD) [13], only limited data are available regarding its direct effect on myocardial function apart from CAD [46]. The metabolic derangement of hypercholesterolemia can result in abnormalities of cardiac function that are likely independent of effects on the vasculature [5]. While single left ventricular (LV) myocytes isolated from hypercholesterolemic rabbits demonstrated a significant reduction in systolic function without any change in blood pressure or LV morphology [4], few data are available from in vivo investigations.

          Speckle tracking echocardiography (STE), a relatively new echocardiographic imaging modalities, offers an objective and quantitative evaluation of global and regional myocardial deformation in longitudinal, radial and circumferential directions [79]. A large amount of published data has described that STE could detect subtle changes in LV function at an early subclinical stage [1013].

          The aim of the present study was to elucidate whether dietary hypercholesterolemia alters LV systolic function independently of CAD using STE in rabbits model and investigate their relationship.

          Methods

          Animal model

          The experimental protocol was approved by a local ethical committee (First Affiliated Hospital, Xinjiang Medical University, Xinjiang, China). Twenty-eight male New Zealand rabbits (1.9-2.3 kg) were housed in separate cages in an environmentally controlled facility (AAALAC accredited) and were given water ad libitum and received humane care in compliance with institutions guidelines. The rabbits were acclimatized to laboratory conditions for 7 days prior to treatment. Eight rabbits were fed normal chow for 3 months as control (group 1) and the remaining 20 accepted an atherogenic diet for 2 months (group 2) or 3 months (group 3). The atherogenic diet contained 84% standard chow diet, 5% lard, 5% egg yolk powder and 2% cholesterol [13]. Diarrhea, appetite and coat color were observed during the experimental period.

          Echocardiographic imaging

          On the day of the study, rabbits fast for approximately 4 h to reduce abdominal distention and to facilitate obtaining the images. Echocardiographic images were acquired after lightly sedated with 10 mg/kg ketamine (Fujian Gutian Pharmaceutical Co., Ltd, China), 1 mg/kg Diazepam (Tianjin Jinyao Amino Acid Co., Ltd, China) and 0.025 mg/kg Atropine (Tianjin Pharmaceutical Group Co., Ltd, China) administered intravenously. The rabbits were placed in prone position without restraint. All images were obtained using a commercial ultrasound machine (Vivid 7 Dimension; GE Vingmed Ultrasound AS, Horten, Norway) with an M5S probe. M- mode images of parasternal long-axis view, B-mode images of apical three-chamber, four-chamber, and two-chamber views, short-axis views at the level of the mitral valve, papillary muscles, and apex were obtained and digitally stored in cine-loop format for off line analysis [14]. LV end-diastolic diameter (LVEDd), LV end-systolic diameter (LVEDs), septal and LV posterior wall thickness, and left atrial anteroposterior diameter (LAD) were measured from standard planes. LV ejection fraction (EF) was calculated with the Teicholz formula [15].

          Strain analysis

          Two-dimensional B-mode images were captured with a frame rate of 50–80 fps and five beats were recorded for analysis. Blinded offline analyses of the short-axis views and apical long-axis views were performed using EchoPAC PC version 6.1.1 (GE Vingmed Ultrasound AS, Horten, Norway). After selecting the best-quality image of the cardiac cycle, the LV endocardial border was manually traced at the end-systolic frame, from which a speckle-tracking region of interest was automatically selected to approximate the myocardium between the endocardium and epicardium [16]. The workstation then computed and generated strain curves. The software automatically divided the sectional image into six segments according to the statement of the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association [17] (Figure 1). Strain curves of three consecutive cardiac cycles and values were imported for further analysis. To determine global longitudinal, circumferential and radial strain, the strain values of the 18 segments were averaged for the apical views or the short-axis views.
          http://static-content.springer.com/image/art%3A10.1186%2F1476-511X-13-128/MediaObjects/12944_2014_Article_1117_Fig1_HTML.jpg
          Figure 1

          Systolic radial stain of the six myocardial segments.

          Blood pressure measurement

          After echocardiographic imaging, blood pressure measurements were made from the central ear artery (CEA) of rabbits using a 20G vascular catheter (Johnson and Johnson, Belgium). The arterial catheter was connected to a pressure transducer (MLT0699, AD Instruments, Pty Ltd, Australia) and an analog-to-digital converter (PowerLab, ML866, AD Instruments, Pty Ltd, Australia). Arterial systolic and diastolic pressure were recorded.

          Cholesterol analysis

          Peripheral blood was collected from ear veins with a 25-gauge needle and syringe at baseline, 2 months and 3 months. Total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were measured with an automated clinical chemistry analyzer (AU680, Beckman Instruments, USA). All rabbits were euthanized at correspnding time and the hearts removed. A segment of myocardial tissue (10 × 3 mm) from the LV free wall was excised. Cholesterol levels were measured in the tissue segment using a cholesterol Kit (EnzyChrom Cholesterol Assay Kit, BioAssay Systems, Hayward, CA).

          Statistical analysis

          SPSS 16.0 (SPSS inc., Chicago, Illinois, USA) was used for statistical analysis. The data were tested for normality and homogeneity of variance. Data are expressed as mean ± standard deviation (SD). One way ANOVA was used to compare the echocardiographic parameters, strain parameters, myocardial and serum cholesterol levels for all three groups. Pearson correlation analysis was done between STE variables and cholesterol levels. For all analyses, a P value < 0.05 was considered significant. Interobserver and intraobserver variability for strain measurements were examined using both Pearson’s bivariate two-tailed correlations and Bland-Altman analysis from 10 randomly selected rabbits.

          Results

          Animal

          Of the 28 experimental rabbits, 1 died in the group 3 due to diarrhea. Heart rates and blood pressure of three groups were similar (P > 0.05, Table 1).
          Table 1

          General characteristics of the study animals

          Parameters

          Group 1 n = 8

          Group 2 n = 10

          Group 3 n = 9

          F-value

          P-value

          HR (beats/min)

          183.50 ± 9.49

          168.30 ± 9.32

          187.89 ± 11.02

          2.21

          0.13

          SBP (mmHg)

          109.88 ± 11.31

          110.50 ± 8.37

          111.22 ± 10.33

          0.12

          0.88

          DBP (mmHg)

          78.25 ± 8.05

          77.50 ± 10.84

          82.67 ± 10.06

          0.73

          0.49

          HR, heart rate; SBP, systolic blood pressure; DBP, diastolic blood pressure.

          Conventional echocardiography

          Echocardiographic measurements of the different groups were shown in Table 2. There were no significant differences in LVEF, LVEDd, LVEDs, IVS, PW and LAD among three groups (P > 0.05).
          Table 2

          Comparison of echocardiographic parameters

          Parameters

          Group1 n = 8

          Group2 n = 10

          Group3 n = 9

          F-value

          P-value

          LVEDd (mm)

          13.14 ± 1.43

          13.51 ± 1.69

          13.33 ± 1.58

          0.12

          0.89

          LVEDs (mm)

          8.62 ± 0.86

          9.00 ± 1.02

          8.81 ± 0.92

          0.37

          0.70

          IVS (mm)

          2.12 ± 0.31

          1.88 ± 0.36

          2.08 ± 0.37

          1.28

          0.30

          PW (mm)

          2.04 ± 0.22

          2.01 ± 0.20

          2.23 ± 0.38

          1.63

          0.22

          LVEF (%)

          67.38 ± 4.63

          65.97 ± 4.61

          66.93 ± 3.73

          0.25

          0.78

          LAD (mm)

          8.84 ± 1.15

          9.94 ± 1.23

          9.42 ± 0.99

          0.66

          0.53

          LVEDd, left-ventricular end-diastolic diameter; LVEDs, left-ventricular end-systolic diameter; EF, ejection fraction; LAD, left-atrial diameter; IVS, ventricular septal end-diastolic thickness; PW, posterior wall end-diastolic thickness.

          Strain measurements

          From a total of 972 analyzed segments, 28 segments were excluded owing to suboptimal myocardial tracking and poor image quality. Regional longitudinal (Table 3) and circumferential (Table 4) strain of LV were significantly reduced in group 3 compared with group 1 and 2. But regional radial strain of LV were significantly increased in group 3 (Table 5). Global longitudinal myocardial deformation of the LV was significantly impaired both in group 2 and 3, while radial deformation was increased in group 3 compared with group 1 and 2. In addition, global circumferential strain was also reduced in group 3 compared with group 1 and 2 (Figure 2).
          Table 3

          Peak systolic longitudinal strain values

          Longitudinal strain (%)

          Group 1 n = 8

          Group 2 n = 10

          Group 3 n = 9

          F-value

          P-value

          A4C septum

               

          Basal segment

          -21.76 ± 3.28

          -21.97 ± 4.08

          -18.87 ± 2.15

          2.240

          0.129

          Mid segment

          -23.40 ± 4.38

          -21.89 ± 3.47

          -18.91 ± 2.20*

          3.493

          0.047

          Apical segment

          -24.54 ± 5.57

          -22.08 ± 4.32

          -19.41 ± 3.06*

          2.685

          0.090

          A4C lateral wall

               

          Basal segment

          -23.64 ± 4.44

          -21.96 ± 3.31

          -18.30 ± 1.69*

          5.382

          0.019

          Mid segment

          -20.88 ± 3.74

          -20.98 ± 3.20

          -18.32 ± 2.01

          1.945

          0.166

          Apical segment

          -22.94 ± 3.36

          -21.90 ± 3.48

          -19.28 ± 4.21

          2.115

          0.143

          A3C posterior wall

               

          Basal segment

          -22.74 ± 3.21

          -20.89 ± 2.38

          -18.87 ± 3.35*

          3.425

          0.050

          Mid segment

          -21.71 ± 2.68

          -22.05 ± 2.65

          -18.57 ± 3.13*

          3.924

          0.034

          Apical segment

          -23.77 ± 2.78

          -21.15 ± 3.47

          -21.60 ± 4.27

          1.327

          0.285

          A3C anterior septum

               

          Basal segment

          -21.31 ± 3.34

          -20.92 ± 3.54

          -19.41 ± 2.79

          0.764

          0.477

          Mid segment

          -21.96 ± 2.95

          -21.09 ± 3.70

          -19.62 ± 3.68

          0.837

          0.446

          Apical segment

          -22.28 ± 2.24

          -22.59 ± 2.87

          -18.86 ± 3.55*

          4.197

          0.028

          A2C inferior wall

               

          Basal segment

          -25.78 ± 4.34

          -20.90 ± 2.74*

          -19.36 ± 3.19*

          7.749

          0.003

          Mid segment

          -23.37 ± 4.53

          -20.02 ± 2.59

          -19.08 ± 3.61*

          3.205

          0.059

          Apical segment

          -24.54 ± 4.51

          -21.23 ± 2.34

          -21.57 ± 4.23

          2.027

          0.155

          A2C anterior wall

               

          Basal segment

          -23.64 ± 4.28

          -21.75 ± 2.34

          -18.96 ± 3.24*

          4.066

          0.031

          Mid segment

          -23.17 ± 3.39

          -23.37 ± 2.68

          -17.82 ± 3.00*

          9.140

          0.001

          Apical segment

          -24.28 ± 5.70

          -23.59 ± 3.90

          -21.10 ± 4.14

          1.075

          0.358

          Data are expressed as mean ± SD. A4C, Apical four-chamber; A3C, apical three-chamber; A2C, apical two-chamber. *p < 0.05 for group 3 and group 2 vs. group 1, p < 0.05 for group 3 vs. group 2.

          Table 4

          Peak systolic circumferental strain values

          Circumferental strain (%)

          Group 1 n = 8

          Group 2 n = 10

          Group 3 n = 9

          F-value

          P-value

          Mitral valve level

               

          Anteroseptal wall

          -30.18 ± 5.52

          -30.33 ± 5.91

          -23.45 ± 6.55*

          3.571

          0.045

          Anterior wall

          -23.76 ± 4.86

          -23.22 ± 4.42

          -20.09 ± 2.33

          1.939

          0.167

          Lateral wall

          -20.63 ± 5.89

          -19.75 ± 3.35

          -19.10 ± 3.19

          0.263

          0.771

          Posterior wall

          -21.40 ± 4.46

          -20.85 ± 4.58

          -18.65 ± 3.25

          0.869

          0.433

          Inferior wall

          -22.58 ± 4.22

          -20.89 ± 4.59

          -17.34 ± 3.73*

          3.215

          0.059

          Septal wall

          -27.99 ± 6.30

          -27.83 ± 6.71

          -21.75 ± 4.45*

          2.937

          0.073

          Papillary level

               

          Anteroseptal wall

          -28.22 ± 7.03

          -29.73 ± 6.00

          -24.80 ± 4.06

          1.619

          0.22

          Anterior wall

          -20.58 ± 3.78

          -22.99 ± 4.44

          -19.76 ± 2.89

          1.776

          0.192

          Lateral wall

          -18.99 ± 3.19

          -20.18 ± 3.17

          -18.31 ± 2.04

          0.982

          0.39

          Posterior wall

          -19.32 ± 3.52

          -19.73 ± 3.31

          -19.45 ± 1.06

          0.047

          0.954

          Inferior wall

          -21.01 ± 3.60

          -20.59 ± 2.33

          -17.19 ± 1.89*

          5.047

          0.015

          Septal wall

          -27.98 ± 7.59

          -28.21 ± 5.53

          -20.66 ± 3.03*

          4.717

          0.019

          Apical level

               

          Anteroseptal wall

          -30.24 ± 6.67

          -28.71 ± 6.29

          -21.53 ± 3.78*

          5.284

          0.013

          Anterior wall

          -25.66 ± 5.46

          -23.68 ± 5.03

          -19.68 ± 2.60*

          3.539

          0.046

          Lateral wall

          -24.88 ± 4.33

          -22.72 ± 6.18

          -19.48 ± 3.25*

          2.192

          0.134

          Posterior wall

          -25.33 ± 5.92

          -23.65 ± 3.84

          -19.49 ± 3.06*

          3.782

          0.038

          Inferior wall

          -25.81 ± 5.45

          -23.46 ± 5.93

          -18.66 ± 2.86*

          4.228

          0.027

          Septal wall

          -26.64 ± 6.78

          -27.42 ± 6.34

          -24.85 ± 5.08

          0.553

          0.582

          Data are expressed as mean ± SD. *p < 0.05 for group 3 and group 2 vs. group 1, p < 0.05 for group 3 vs. group 2.

          Table 5

          Peak systolic radial strain values

          Radial strain (%)

          Group 1 n = 8

          Group 2 n = 10

          Group 3 n = 9

          F-value

          P-value

          Mitral valve level

               

          Anteroseptal wall

          36.84 ± 6.98

          38.88 ± 6.16

          45.48 ± 6.85*

          3.756

          0.039

          Anterior wall

          37.92 ± 7.15

          40.48 ± 8.06

          44.77 ± 9.82

          1.368

          0.275

          Lateral wall

          41.65 ± 7.78

          42.02 ± 9.12

          46.48 ± 9.37

          0.765

          0.477

          Posterior wall

          39.65 ± 5.41

          44.31 ± 7.06

          49.07 ± 6.21*

          4.426

          0.024

          Inferior wall

          40.92 ± 5.31

          42.54 ± 7.64

          50.13 ± 7.02*

          4.231

          0.027

          Septal wall

          38.09 ± 7.21

          40.84 ± 7.21

          47.40 ± 5.41*

          4.098

          0.03

          Papillary level

               

          Anteroseptal wall

          37.41 ± 5.01

          38.11 ± 5.38

          44.81 ± 10.12*

          2.726

          0.087

          Anterior wall

          37.06 ± 7.45

          37.83 ± 6.56

          39.28 ± 7.31

          0.205

          0.816

          Lateral wall

          42.32 ± 7.81

          39.45 ± 7.27

          42.05 ± 9.37

          0.351

          0.708

          Posterior wall

          42.54 ± 7.14

          44.24 ± 3.81

          46.22 ± 11.70

          0.432

          0.654

          Inferior wall

          43.18 ± 8.54

          42.40 ± 4.87

          45.67 ± 6.38

          0.574

          0.571

          Septal wall

          39.85 ± 8.45

          41.14 ± 6.87

          48.49 ± 6.96*

          3.23

          0.058

          Apical level

               

          Anteroseptal wall

          39.10 ± 6.70

          38.63 ± 5.90

          43.96 ± 6.63

          1.802

          0.187

          Anterior wall

          37.29 ± 6.44

          38.84 ± 5.84

          44.71 ± 4.59*

          3.88

          0.035

          Lateral wall

          43.85 ± 8.84

          40.85 ± 3.97

          47.66 ± 9.67*

          3.159

          0.061

          Posterior wall

          41.17 ± 7.37

          41.74 ± 6.88

          44.07 ± 12.15

          0.241

          0.788

          Inferior wall

          44.52 ± 6.66

          42.14 ± 8.85

          44.90 ± 7.49

          0.336

          0.718

          Septal wall

          42.44 ± 6.06

          38.34 ± 5.84

          46.96 ± 10.41

          2.88

          0.076

          Data are expressed as mean ± SD. * p < 0.05 for group 3 and group 2 vs. group 1, p < 0.05 for group 3 vs. group 2.

          http://static-content.springer.com/image/art%3A10.1186%2F1476-511X-13-128/MediaObjects/12944_2014_Article_1117_Fig2_HTML.jpg
          Figure 2

          Global peak systolic longitudinal, circumferential and radial strain in the three groups. * p < 0.001 for group 3 vs. group 2 and group 1. p < 0.05 for group 2 vs group 1.

          Serum and tissue cholesterol profiles

          The serum cholesterol profiles of the three groups after experiment were shown in Table 6. There was a statistically significant increase in serum TC, LDL-C and tissue cholesterol levels in animals fed with cholesterol enriched diet compared with the control group (p <0.05). Morerove, the concentration of cholesterol increased with feeding duration (p <0.05).
          Table 6

          Serum and tissue cholesterol profiles

          Parameters

          Group 1 n = 8

          Group 2 n = 10

          Group 3 n = 9

          F-value

          P-value

          Serum TC (mmol/L)

          2.07 ± 0.60

          24.15 ± 5.36*

          34.74 ± 10.40*

          191.27

          0.000

          Serum LDL-C (mmol/L)

          1.13 ± 0.54

          10.73 ± 3.32*

          31.62 ± 3.68*

          229.60

          0.000

          Tissue cholesterol(μmol/g)

          0.86 ± 0.29

          2.22 ± 0.62*

          4.92 ± 1.63*

          34.68

          0.000

          Data are expressed as mean ± SD. TC, total cholesterol; LDL-C, low density lipoprotein cholesterol.

          * p < 0.05 for group 3 and group 2 vs. group 1, p < 0.05 for group 3 vs. group 2.

          Correlation between strain parameters and cholesterol levels

          The correlation between strain parameters and cholesterol were shown in Table 7. There was significant inverse correlation between global longitudinal strain and serum TC, LDL-C as well as myocardial cholesterol levels. (r = - 0.723, P < 0.001; r = - 0.794, P < 0.001; r = - 0.70, P < 0.001). A significant negative correlation was also noted between global circumferential strain and serum TC, LDL-C as well as myocardial cholesterol levels. (r = - 0.518, P = 0 .007; r = - 0.691, P < 0.001; r = - 0.659, P < 0.001). A significant positive correlation was found between radial strain and serum TC, LDL-C as well as myocardial cholesterol levels. (r = 0.432, P = 0.028; r = 0.602, P = 0.001; r = 0.469, P = 0.016).
          Table 7

          Correlation between strain paramters and cholesterol

          Strain parameters

          Serum TC

          Serum LDL -C

          Tissue cholesterol

           

          r

          p

          r

          p

          r

          p

          GLS

          -0.723

          0.000

          -0.794

          0.000

          -0.700

          0.000

          GRS

          0.432

          0.028

          0.602

          0.001

          0.469

          0.016

          GCS

          -0.518

          0.007

          -0.691

          0.000

          -0.659

          0.000

          GLS, global longitudinal strain; GRS, global radial strain; GCS, global circumferential strain; TC, total cholesterol; LDL-C, low density lipoprotein cholesterol.

          Reproducibility

          The results showed very good intra-observer variability for longitudinal, circumferential and radial strain rate (r = 0.817, P = 0.004; r = 0.798, P = 0.006; r = 0.868, P = 0.001). The Bland-Altman plots demonstrated acceptable inter-observer variability for all strain parameters (Figure 3).
          http://static-content.springer.com/image/art%3A10.1186%2F1476-511X-13-128/MediaObjects/12944_2014_Article_1117_Fig3_HTML.jpg
          Figure 3

          Inter-observer variability for global longitudinal (left), circumferential (middle) and radial strain (right).

          Discussion

          To the best of our knowledge, the present study is the first to comprehensively compare strain parameters-derived STI with the levels of serum and myocardial cholesterol in diet-induced expeimental hypercholesterolemia. Although previous experimental studies have shown that diet-induced hypercholesterolemia resulted in contractile reduction of single ventricular myocyte without any change in pressure or LV morphology [4], few data are available from in vivo investigations. The present study displayed the application of STE as a noninvasive imaging technique to elucidate the direct effect of hypercholesterolemia on LV myocardial deformation in a rabbit model.

          In our study, there were no significant differences in LV morphology, EF and blood pressure among groups, whereas LV strain was found to be reduced in the hypercholesterolemic rabbits. Previous studies failed to show abnormalities using EF, which may be due to EF reflects the whole LV systolic function, under the influence of pre and afterload [18]. With the application of advanced techniques, such as strain, strain rate, incipient systolic dysfunction has been detected in subclinical diseases [19]. Moreover, our analysis indicates that longitudinal dysfunction are the first appeared, followed by circumferential, which suggest the importance of longitudinal strain in the assessment of LV systolic dysfunction in subclinical stage.

          Whether similar changes occur in humans with hypercholesterolemia can not confirm from our study. However, a recent human study demontrated longitudinal and circumferential deformations were both impaired in the children with heterozygous familiar hypercholesterolemia [20]. Thus, we believe that the abnormalities we found in rabbit models with hypercholesterolemia indicate an early sign of hypercholesterolemia-induced myocardial dysfunction, in agreement with the in vitro expriments [4].

          Interestingly, our study demonstrates that the increased radial deformation make up for impaired longitudinal and circumferential strain in rabbit hypercholesterolemic models to maintain LVEF. This finding is consistent with prior reports in children with heterozygous familial hypercholesterolemia and other preclinical diseases [14, 20, 21]. The potential mechanism by which hypercholesterolemia causes the increase in radial deformation remains unclear. A possible explanation could be the realignments of myocardial fiber orientation in the outer half of the myocardium may contribute to “transmural compensation” by less impaired epicardial fibers [22].

          In the present study, a significant negative correlation were found between global longitudinal strain and serum cholesterol level as well as myocardial cholesterol levels. These results indicate that the cholesterol accumulated in the myocardium may be responsible for a reduction in myocardial strain. Similar to our study, Wang et al. [23] reported a positive correlation between serum HDL levels and LVEF in human subjects with serum hypercholesterolemia even in the absence of angiographic evidence of CAD.

          The precise mechanism responsible for the association between cholesterol level and impaired myocardial deformation cannot be determined from our study. However, several mechanisms have been proposed to explain LV dysfunction induced by hypercholesterolemia: (1) increased cardiac oxidative stress [24], (2) alteration of the myocardial energy metabolism [22], (3) changes in myosin heavy-chain isoform expression patterns [4], (4) down-regulation and redistribution of connexin-43 expression in myocardium [25], and (5) impaired activation of myocardial adenosine triphosphate-sensitive potassium channels [19]. These mechanisms may represent the basis for a “hypercholesterolemic cardiomyopathy [26].

          Study limitations

          As a limitations of our study, administration of ketamine- Diazepam - Atropine combinations induces mild bradycardia, which slightly alters cardiac function. In addition, LV diastolic function, rotation and torsion mechanics are potentially very important features for the comprehensive understanding of myocardial tissue damage; therefore, lack of measurement of diastolic function, rotation and torsion was another limitation of the present study.

          Conclusion

          Hypercholesterolemia was significantly associated with LV myocardial functional alterations apart from CAD. The findings also indicate that decreases in longitudinal was the first appeared, followed by circumferential, and was compensated for by increasing radial strain. Thus, the application of STE may provide noninvasive functional insight into disease progression or recovery in reponse to therapeutic intervention.

          Abbreviations

          CAD: 

          Coronary artery disease

          STE: 

          Speckle-tracking echocardiography

          LV: 

          Left ventricular

          TC: 

          Total cholesterol

          LDL-C: 

          Low density lipoprotein cholesterol

          LVEDd: 

          LV end-diastolic diameter

          LVEDs: 

          LV end-systolic diameter

          CEA: 

          Central ear artery.

          Declarations

          Acknowledgement

          This study was supported by the National Natural Science Foundation of China (No. 81060121). The authors wish to thank Tao Jiang for excellent technical assistance.

          Authors’ Affiliations

          (1)
          Department of Echocardiography, Center of Medical Ultrasound, First Affiliated Hospital of Xinjiang Medical University

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          © Liu et al.; licensee BioMed Central Ltd. 2014

          This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​4.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://​creativecommons.​org/​publicdomain/​zero/​1.​0/​) applies to the data made available in this article, unless otherwise stated.

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