Abstract 11100: Short-term Pravastatin Amplifies Cardiac Regeneration in Swine with Ischemic Cardiomyopathy
Background: LV function improves after short-term administration of a variety of statins but large clinical trials have failed to demonstrate a beneficial effect of chronic treatment in patients with heart failure. The duration of therapy could alter the relative balance between beneficial proliferative actions related to upregaulating Akt, vs. antiproliferative effects related to downregulating the rho kinase pathway. We therefore tested the hypothesis that short-term statin treatment could improve cardiac function and myocyte proliferation more than chronic treatment in swine with ischemic cardiomyopathy.
Methods: Swine with ischemic cardiomyopathy from chronic LAD and LCX stenoses were treated with pravastatin (80mg/day) for 2 weeks (Short-term, n=8) or 4 weeks (Chronic, n=8). Data were compared to untreated animals with ischemic cardiomyopathy (n=6). We assessed function (echocardiogram) at baseline and 4-weeks after beginning the protocols. Histological samples quantified myocytes in the cell cycle (Ki-67), mitosis (phospho-Histone H3; pHH3) along with myocyte nuclear density and myocyte diameter to assess cumulative myocyte proliferation.
Results: The Table compares results in each group. Short-term pravastatin increased regional function more than chronic pravastatin (p<0.05). Likewise, short-term pravastatin increased both Ki-67+ and pHH3+ myocytes more than chronic pravastatin or untreated ischemic cardiomyopathy animals. As a result, myocyte nuclear density was higher and myocyte size smaller after short-term vs chronic statin therapy.
Conclusions: These data indicate that in comparison to chronic therapy, short-term pravastatin therapy 1.) Amplifies the number of Ki67 and pHH3 positive myocytes in the heart and 2.) Increases myocyte nuclear density with reduced myocyte size. The data support the notion that ”pulse statin therapy” may be more effective than continuous long-term therapy in improving LV dysfunction.
- Cardiac regeneration
- Stem/progenitor cells
- Regenerative medicine stem cells
- Cardiovascular development
- © 2012 by American Heart Association, Inc.