Abstract
The effects of the chronic administration of cholesterol on the stunned myocardium have not been studied. The objective was to determine the effect of a cholesterol enriched diet on postischemic ventricular dysfunction. In group 1 (G1, n = 7 isolated rabbit hearts underwent a follow up of ventricular function during 30 min in aerobic conditions. In group 2 (G2, n = 6) G1 was repeated but the animals were subjected to a 1% cholesterol enriched diet during 4 weeks (hypercholesterolemic animals). In group 3 (G3, n = 8) hearts underwent 15 min of global ischemia followed by 30 min of reperfusion. In Group 4 (G4, n = 11) G3 was repeated, but in hypercholesterolemic animals. Since cholesterol decreased the inotropism in basal situation, and this makes the comparison between groups difficult, we performed a Group 5 (G5, n = 7), in which G4 protocol was repeated but isoproterenol (8 μg/kg/min) was administered 10 min before ischemia, in order to match the preischemic inotropic state with respect to the normocholesterolemic ones. G1 and G2 maintained a stable inotropism during the 30 min of perfusion. The preischemic left ventricular developed pressure (LVDP) in G3 and G4 was 91.4± 4.3 and 70.8± 3.4 mmHg (p< 0.05), respectively, and after 30 min of reperfusion differences were not observed between G3 and G4. Nevertheless, when LVDP is expressed as a percentage, we detected an attenuation of postischemic systolic alterations in hypercholesterolemic animals (67.3± 3.6 in G4 vs. 90.8± 3.1% in G3, p< 0.05). When LVDP in G5 was increased until matching the one of G3, there were no differences after 30 min of reperfusion. Left ventricular end diastolic pressure increased 285± 46%, 61± 25% (p< 0.05 vs. G3 and G5) and 216± 25% in G3, G4 and G5 at 30 min of reperfusion. There were no differences either in the values of tau or infarct size between groups. Thus, in hypercholesterolemic animals, a decrease of the preischemic inotropism exists and there is an attenuation of the stunned myocardium. When contractility of the normo and hypercholesterolemic animals is matched, the beneficial effect disappears.
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Heyndrickx GR, Millard R, McRitchie J, Maroko P, Vatner S: Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dog. J Clin Invest 56: 978–985, 1975
Bolli R: Mechanism of myocardial “stunning”. Circulation 8: 723–738, 1990
Braunwald E, Kloner R: The stunned myocardium: Prolonged, postischemic ventricular dysfunction. Circulation 6: 1146–1149, 1992
Mosca SM, Gelpi RJ, Cingolani H: Dissociation between myocardial relaxation and diastolic stiffness in the stunned heart: Its prevention by preconditioning. Mol Cell Biochem 129: 171–178, 1993
Charlat ML, O’Neill P, Hartley CJ, Roberts R, Bolli R: Prolongued abnormalities of left ventricular diastolic wall thinning in the stunned myocardium in conscious dogs: Time course and relation to systolic function. J Am Coll Cardiol 13: 185–194, 1989
Hoshida S, Yamashita N, Kuzuya T, Hori M: Differential effects of long-term renin-angiotensin system blockade on limitation of infarct size in cholesterol-fed rabbits. Atherosclerosis 149(2): 287–294, 2000
Hoshida S, Yamashita N, Kuzuya T, Hori M: Reduction in infarct size by chronic amlodipine treatment in cholesterol-fed rabbits. Atherosclerosis 138(1): 163–170, 1998
Li G, Tokuno S, Tahep ld P, Vaage J, Lowbeer C, Valen G: Preconditioning protects the severely atherosclerotic mouse heart. Ann Thorac Surg 71(4): 1296–1303, 2001
Le Grand B, Viê B, Fauré P, Degryse AD, Mouillard O, John G: Increased resistance to ischemic injury in the isolated perfused atherosclerotic heart of the cholesterol-fed rabbit. Cardiovasc Res 30: 689–696, 1995
Van de Velde M, De Wolff M: Leather HA, Wouters PF: Effects of lipids on the functional and metabolic recovery from global myocardial stunning in isolated rabbit hearts. Cardiovasc Res 48: 129–137, 2000
Bolli R: Basic and clinical aspects of myocardial stunning. Prog Cardiovasc Dis 40(6): 477–516, 1998
MPharm HS, Arneja AS, Dhalla NS: Role of cholesterol in cardiovascular dysfunction. Can J Cardiol 20(3): 333–346, 2004
Peterson DW, Griffith DW Jr, Napolitano CA: Decreased myocardial contractility in papillary muscles from atherosclerotic rabbits. Circ Res 45(3): 338–346, 1979
Shah KR, Kolar F, Beamish RE, Dhalla NS: Depression in cardiac contractile force induced by cholesterol. Cardioscience 1: 255–259, 1990
Huang KE, Walker F, Hanley J, Narula SR: Cardiac systolic and diastolic dysfunction after a cholesterol-rich diet. Circulation 109: 97–102, 2004
Girod WG, Jones SP, Sieber N, Aw TY, Lefer D: Effects of hypercholesterolemia on myocardial ischemia-reperfusion injury in LDL receptor-deficient mice. Atheros Thromb Vasc Biol 19: 2776–2781, 1999
Peterson DW, Napolitano CA, Griffith DW Jr: Spontaneous mechanical alternans in papillary muscles from atherosclerotic rabbits. Am J Physiol 39(5): H674–H680, 1980
Gelpi RJ, Mosca S, Cingolani H: The effects of bay K 8644 on diastolic function in the dog heart. J Mol Cell Cardiol 22: 1285–1296, 1990
Assman G, Schriewer H, Schmitz Gl, Hagele EO: Quantification of high density lipoprotein cholesterol by precipitation with Phosphotungstic acid-MgCl2. Clin Chem 29: 2026–2030, 1983
Assman G, Jabs H, Kohnert U, Nolte W, Schriewer H: LDL (low density lipoprotein) cholesterol determination in blood serum following precipitation of LDL with poly(vinyl sulphate). Clin Chim Acta 140: 77–83, 1984
Toleikis PM, Tomlinson CW: Improved functional recovery of the atherosclerotic rabbit heart subjected to normothermic global ischemia. Can J Cardiol 3(7): 345–350, 1987
Pfeiffer C, Flemming B, Gunther J, Vetter R, Goos H, Pfeifer K: Changes in the excitation contraction coupling in the myocardium of rabbits fed a cholesterol-containing diet. Acta Biol Med Ger 37(7): 1037–1047, 1978
Calabresi L, Rossoni G, Gomaraschi M, Sisto F, Berti F, Franceschini G: High-density lipoproteins protect isolated rat hearts from ischemia-reperfusion injury by reducing cardiac tumor necrosis factor-α content and enhancing prostaglandin release. Circ Res 92: 330–337, 2003
Bastiaanse EM, Atsma DE, Kuijpers MM, Van der Laarse A: The effect of sarcolemmal cholesterol content on intracellular calcium ion concentration in cultured cardiomyocytes. Arch Biochem Biophys 313(1): 58–63, 1994
Peterson DW, Napolitano CA, Griffith DW Jr: Spontaneous mechanical alternans in papillary muscles from atherosclerotic rabbits. Am J Physiol 239(5): H674–H680, 1980
Edelsteinova S, Svec P, Augustiniova B, Devecka V, Pazin-Hrickova E: Biochemical, structural and ultrastructural changes in the Prague hereditary hypercholesterolemic (PHHC) rat hearts after the long treatment with calcium channel blockers. Pharmazie 48(10): 769–772, 1993
Ladilov Y, Efe O, Schafer C, Rother B, Kasseckert S, Abdallah Y, Meuter K, Dieter Schluter K, Piper HM: Reoxygenation-induced rigor-type contracture. J Mol Cell Cardiol 35(12): 1481–1490, 2003
Kalaivanisailaja J, Manju V, Nalini N: Lipid profile in mice fed a high-fat diet after exogenous leptin administration. Pol J Pharmacol 55(5): 763–769, 2003
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D’Annunzio, V., Donato, M., Sabán, M. et al. Hypercholesterolemia attenuates postischemic ventricular dysfunction in the isolated rabbit heart. Mol Cell Biochem 273, 137–143 (2005). https://doi.org/10.1007/s11010-005-8264-6
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DOI: https://doi.org/10.1007/s11010-005-8264-6