Issn Print: 0265-0215

Publication Date: 2007/06/01


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Maintaining normoglycemia and not glycemia-independent actions of insulin preserves myocardial performance by protecting mitochondrial function: BAPC1-2

B. Ellger; I. Vanhorebeek; Y. Debaveye; R. De Voss; G. Van den Berghe

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Background and Goal of Study: Intensive insulin therapy (IIT) reduces mortality and morbidity of critically ill patients. Several investigations suggest that insulin might ameliorate myocardial contractility independently of its actions on blood glucose.
Materials and Methods: In a rabbit model of prolonged critical illness using a 4-arm design (n = 8 per group), blood glucose (normal NG-high HG) and plasma insulin levels (normal NI-high HI) were independently manipulated over 7 days, to elucidate relative impact of maintaining normoglycemia and glycemia-independent actions of insulin on left ventricular contractility in an open chest preparation, cellular ultra-structure by electron microscopy, the activities of the respiratory chain complexes in biopsies from the left ventricle, and plasma levels of serum heart-fatty-acid-binding-protein.
Results and Discussions: Contractility increased in HI/NG animals and deteriorated in HI/HG animals compared to other groups and healthy controls. Cardiac output and surrogate parameters of preload and afterload did not differ among groups. Electron microscopy revealed severely damaged mitochondria in cardiac myocytes in particular in HI/HG rabbits. Concomitantly, the activities of complex I, III and V were compromised in the left ventricle biopsies of both hyperglycemic groups, in particular in the HI/HG group. Both normoglycemic groups revealed no changes in ultra-structure and complex activity compared to healthy controls. Compromised mitochondrial enzyme activities correlated with cardiac damage assessed by plasma levels of heart-fatty-acid-binding-protein, suggesting that mitochondrial protection mediated part of the prevention of organ failure.
Conclusions: In our animal model of prolonged critical illness, insulin ameliorated myocardial contractility but only when normoglycemia was maintained concomitantly. Maintaining normoglycemia and not glycemia-independent actions of insulin appear crucial for preserving mitochondrial function in the myocardium.
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