Effect of Atorvastatin on Cardiac Remodelling and Mortality in Rats Following Hyperglycemia and Myocardial Infarction

• Published in: International journal of cardiology 2010-09, Vol.143 (3), p.353-360
• Main Authors: Martin, Jennifer H, Connelly, Kim A, Boyle, Andrew, Kompa, Andrew, Zhang, Yuan, Kelly, Darren, Gilbert, Richard E, Krum, Henry
• Format: Article
• Language: English
• Subjects: Animals; Atorvastatin Calcium; Biological and medical sciences; Body Weight - drug effects; Cardiac remodelling; Cardiac Volume - drug effects; Cardiology. Vascular system; Cardiovascular; Collagen Type I - metabolism; Collagen Type III - metabolism; Coronary heart disease; Diabetes; Diabetes Mellitus, Experimental - mortality; Diabetes. Impaired glucose tolerance; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fibrosis; Heart; Heptanoic Acids - pharmacology; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Hyperglycemia - mortality; Medical sciences; Myocardial Infarction - drug therapy; Myocardial Infarction - mortality; Myocardial Infarction - pathology; Myocarditis. Cardiomyopathies; Myocardium - metabolism; Myocardium - pathology; Pyrroles - pharmacology; Rats; Rats, Sprague-Dawley; Ventricular Remodeling - drug effects
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2009.03.098

Abstract Effect of HMGCoA Reductase Inhibitors on Cardiac Remodelling and Mortality in Rats. Following Hyperglycemia and Myocardial Infarction. Aims The presence of diabetes mellitus (DM) in patients with myocardial infarction (MI) increases mortality, due in part to the presence of known cardiovascular risk factors. However little is known about the impact of DM on cardiac remodelling and on clinical outcomes. We aimed to investigate whether hyperglycaemia may adversely and additionally affect LV remodelling post-MI, and whether the addition of a statin, known to reduce mortality both post MI and in humans with DM, has an effect on these outcomes. Methods: Eight week old Sprague-Dawley rats were allocated to 5 groups - control (non-DM)/sham, control-MI, DM-sham, DM-MI and DM-MI with statin gavage (DM-MI/ATV). Echocardiogram and invasive pressure volume analysis were performed prior to sacrifice for estimation of cardiac function. Tissue was analysed for total cardiac collagen, collagen I and III. Results: Hyperglycaemia in the remodelling period significantly increased mortality (70% survival in the C-MI group vs 27% in the DM-MI group), worsened cardiac function and increased fibrosis. All of these variables were attenuated by the addition of a statin. Conclusion: Hyperglycaemia increased mortality in MI and exacerbated LV remodeling, and this was attenuated with statin use. This study confirms the importance of early and intensive treatment of hyperglycaemia in patients with MI and suggests that in humans with both DM and MI the addition of a statin may be beneficial.