Abstract 4744: Rosuvastatin Does Not Improve Myocardial Function, Perfusion, or Stimulate Myocyte Proliferation in Swine With Hibernating Myocardium
Background: Recent large clinical trials have failed to demonstrate an effect of the HMG-CoA reductase inhibitor rosuvastatin in patients with systolic heart failure. In contrast, in swine with hibernating myocardium, pravastatin improves myocardial function by mobilizing progenitor cells and stimulating myocytes to reenter the cardiac cell cycle. We tested the hypothesis that these discordant effects reflect a differential ability of statins to facilitate endogenous cardiac stem cell proliferation.
Methods: Swine with a chronic LAD stenosis and collateral-dependent hibernating myocardium were studied in the propofol sedated state 4-months after instrumentation. Flow and function were compared at baseline and 4-weeks after rosuvastatin (40mg/day p.o., n=6). Histological analysis was performed to quantify myocyte nuclear density. The frequency of myocytes in the growth phase of the cell cycle was evaluated by Ki-67. Myocardial progenitor cells were quantified using the cell surface marker ckit and analyzed by confocal microscopy. Results were compared to untreated (n=10) and historical animals treated with pravastatin (160 mg/day, p.o., n=12) (Table⇓).
Results: Neither pravastatin nor rosuvastatin affected vasodilated myocardial perfusion (relative LAD/Remote). While pravastatin increased myocyte proliferation, there was no effect of rosuvastatin on function and myocyte nuclear density was not changed from untreated animals. These observations reflected the fact that, in contrast to pravastatin, rosuvastatin did not increase ckit+ cells or Ki67+ myocytes.
Conclusion: These data indicate that the ability of statins to stimulate myocyte proliferation and improve function in viable chronically dysfunctional myocardium is not a class effect. The inability of rosuvastatin to improve function and stimulate myocyte proliferation may be responsible for its inability to impact survival in the GISI-HF and CORONA trials.