Effect of atorvastatin on cardiac remodelling and mortality in rats following hyperglycemia and myocardial infarction.
Effect of HMGCoA Reductase Inhibitors on Cardiac Remodelling and Mortality in Rats. Following Hyperglycemia and Myocardial Infarction.


OBJECTIVE
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.


CONCLUSIONS
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.
Martin
Jennifer H
JH
Diamantina Institute, The University of Queensland, Royal Brisbane and Women's Hospital, Queensland, Australia. Jennifer_H_Martin@health.qld.gov.au
Connelly
Kim A
KA
Boyle
Andrew
A
Kompa
Andrew
A
Zhang
Yuan
Y
Kelly
Darren
D
Gilbert
Richard E
RE
Krum
Henry
H
D000818:Animals; D000069059:Atorvastatin; D001835:Body Weight / Q000187:drug effects; D002306:Cardiac Volume / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000401:mortality; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D006943:Hyperglycemia / Q000401:mortality*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020257:Ventricular Remodeling / Q000187:drug effects*
D024042:Collagen Type I; D024061:Collagen Type III; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin