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Different Effects of a High-Cholesterol Diet on Ischemic Cardiac Dysfunction and Remodeling Induced by Coronary Stenosis and Coronary Occlusion

First Department of Internal Medicine, Fukushima Medical University, Fukushima, Japan

View larger version (30K): [in a new window]   Figure 1 A diagram of experimental groups. Echocardiography (not shown in the figure) was performed before, 4, 8, and 12 weeks after surgery. In the normal chow diet (NCD)- and high-cholesterol diet (HCD)-coronary stenosis (CS) groups with tetrahydrobiopterin supplementation, echocardiography was performed before and four weeks after CS. *Myocardial oxygen consumption (MVO2) study not done; **among total n = 13, n = 6 for NCD- or HCD-sham without ischemic preconditioning (IPC) (Fig. 6) and n = 7 for NCD- and HCD-sham with IPC. CFR = coronary flow reserve; ECG = electrocardiogram; ED1 = the antibodies against monocytes; MCP1 = monocyte chemoattractant protein-1; MI = myocardial infarction; PKC = protein kinase C.

View larger version (34K): [in a new window]   Figure 2 Effects of NCD and HCD on left ventricular echocardiographic findings in rats with coronary stenosis (left) and MI (right). n = 24 to 34; for statistical analysis, n = 33 each (CS groups vs. sham, NCD vs. HCD) and 24 each (MI groups) for Bonferroni’s post-hoc comparisons. *p < 0.01 vs. corresponding sham; p < 0.01 NCD-CS. (n) indicates survivors for 12 weeks. Open circles = NCD-sham (n = 33); open squares = NCD-CS (n = 34) or -MI (n = 26); closed circles = HCD-sham (n = 33); closed squares = HCD-CS (n = 34) or –MI (n = 24). LVEDD = left ventricular end-diastolic diameter; LVESD = left ventricular end-systolic diameter; LVEF = left ventricular ejection fraction.; other abbreviations as in Figure 1.

View larger version (13K): [in a new window]   Figure 3 Effects of tetrahydrobiopterin (n = 10 each) on left ventricular echocardiographic findings four weeks after CS. The data on NCD- and HCD-sham (n = 33 each) are the same as those in Figure 2 (for statistical analysis, n = 10 each in other four groups for Bonferroni’s post-hoc comparisons). Open circles = NCD; closed circles = HCD. N = 33 each in NCD- and HCD-sham. N = 10 each in NCD- and HCD-CS. N = 10 each in NCD- and HCD-CS with tetrahydrobiopterin. *p < 0.01, p < 0.05 vs. corresponding sham; p < 0.01, p < 0.05 vs. corresponding CS; ||p < 0.01, ¶p < 0.05 vs. corresponding NCD. LV = left ventricular; other abbreviations as in Figure 1.

View larger version (35K): [in a new window]   Figure 4 Myocardial blood flow and coronary flow reserve one and 12 weeks after CS or sham surgery (n = 7 each one week after surgery, and n = 10 to 14 at 12 weeks after surgery; for statistical analysis at 12 weeks, n = 10 each for Bonferroni’s post-hoc comparisons). *p < 0.01 CS vs. corresponding sham; p < 0.01, p < 0.05 HCD vs. corresponding NCD; p < 0.01 vs. corresponding group without BH4. BH4 = tetrahydrobiopterin; other abbreviations as in Figure 1.

View larger version (32K): [in a new window]   Figure 5 Changes in the in vitro MVO2 by bradykinin and sodium nitroprusside 24 h after sham surgery or CS. (Left) The effect of 10–4 mol/l L-NAME on the in vitro MVO2 changes by bradykinin and sodium nitroprusside in the sham group with NCD and HCD. (Right) The effect of BH4 on those in the CS groups with NCD and HCD (n = 7 in each group for Bonferroni’s post-hoc comparisons). *p < 0.01 vs. baseline; p < 0.01 vs. NCD-sham; p < 0.05 HCD-CS vs. NCD-CS. P < 0.05 NCD-CS + BH4 vs. NCD-CS; p < 0.01 HCD-CS + BH4 vs. HCD-CS (asterisks not shown on right panel). BK = bradykinin; SNP = sodium nitroprusside; other abbreviations as in Figures 1 and 4.

View larger version (17K): [in a new window]   Figure 6 Protein kinase C (PKC)- translocation ratios in myocardium at risk one week after CS or sham surgery (n = 6 each for Bonferroni’s post-hoc comparisons). Ischemic preconditioning (IPC) (n = 7 each) was used as a positive control for PKC- activation by ischemia. n = 6 each group except n = 7 each in the NCD-sham + IPC and HCD-sham + IPC groups. *p < 0.01 vs. corresponding sham; p < 0.01, p < 0.05 vs. corresponding CS; p < 0.05 vs. NCD-CS. Abbreviations as in Figure 1.

View larger version (66K): [in a new window]   Figure 7 (A, left upper panels) Histopathologic findings (hematoxylin-eosin) of the anterior wall of the rats with 12-week CS and with HCD (A-1, magnification x40) and NCD (A-2, magnification x40), as well as MCP-1–positive coronary microvessels and infiltrating cells in rats with HCD (A-3, magnification x200). (B, right upper panel, and C, right lower panel) MCP-1 and ED-1 positivity in myocardium at risk in rats with NCD and HCD in the sham, CS, and CS plus tetrahydrobiopterin (BH4) groups at one day and one week (n = 7 each) and 12 weeks after surgery (n = 10 to 13, but n = 10 each for Bonferroni’s post-hoc comparisons). *p < 0.01, p < 0.05 vs. corresponding sham; p < 0.01 BH4 vs. corresponding CS without BH4; p < 0.01 vs. corresponding NCD group. Abbreviations as in Figures 1 and 4.