title: [The effect of type II diabetes and the metabolic syndrome on cardiac second window preconditioning].
abstract: Preconditioning is the most powerful endogenous mechanism, to protect the heart against ischemic damage. Conflicting data are published whether preconditioning can be induced in case of diabetes and the metabolic syndrome, which are clinically very relevant conditions. If preconditioning could be induced consistently and chronically in this population, an important reduction of surgical morbidity and mortality could be reached. In this project we induced hypoxic preconditioning in mice and used cardiac pressure-conductance catheterisation and infarct size as outcome parameters. In the first part, we found that hypoxic preconditioning was capable to reduce infarct size with 40% and preserve the load-independent parameters with 33% after coronary occlusion. A DKO (double knock-out: ob/ob; LDLR-/-) model for the metabolic syndrome developed a larger infarct size and had a reduced contractility. No preconditioning could be induced in this model. To detect the determing factor of the resistance to preconditioning, we used single knock-out models. A comparable preconditioning effect of wild type mice could be induced in the lipoprotein receptor deficient (LDLR-/-) model for dyslipidemia. The leptin deficient (ob/ob) model, characterized by insulin resistance and abdominal obesity had, identically to the DKO model, a larger infarct size. A second window of preconditioning could be induced, although it was less pronounced than the wild type and LDLR-/- model. Insulin resistance and abdominal obesity could be identified as the major factor in the resistance to preconditioning.
authors.affiliation: Afdeling Experimentele Cardiale Heelkunde, Departement Hart- en Vaatziekten, KULeuven Minderbroedersstraat 19, Provisorium I, B 3000 Leuven.
authors.forename: G
authors.initials: G
authors.lastname: Van Der Mieren
authors.forename: W
authors.initials: W
authors.lastname: Flameng
authors.forename: P
authors.initials: P
authors.lastname: Herijgers
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000503:physiopathology*; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D024821:Metabolic Syndrome / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D018110:Receptors, Lipoprotein / Q000172:deficiency* / Q000235:genetics
chemical_list: D018110:Receptors, Lipoprotein