April 22, 2026Journal of the American College of Cardiology
Atorvastatin, administered at the onset of reperfusion, and independent oflipid lowering, protects the myocardiumby up-regulating a pro-survival pathway
Key result
Atorvastatin at reperfusion cuts infarct size ~52% in mouse hearts via PI3K/Akt and eNOS.
- P<0.01
Why the study?
Statins are proposed to have cardioprotective effects beyond cholesterol lowering via PI3K and Akt recruitment, but whether atorvastatin limits myocardial necrosis when administered at reperfusion was unknown.
Does atorvastatin reduce infarct size in isolated perfused mouse hearts subjected to ischemia and reperfusion?
Population
Isolated perfused mouse hearts subjected to 35 min of global ischemia
Comparison
Incremental concentrations of atorvastatin vs control or with wortmannin
Design
Ex vivo animal experimental study
Follow-up
30 min of reperfusion
Authors
Discussion
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Implication
Atorvastatin at reperfusion has no current clinical role; leaves open PI3K/Akt/eNOS translation to human cardioprotection.
Key Points
- This study aims to determine if atorvastatin limits myocardial necrosis during reperfusion without relying solely on cholesterol reduction.
- Isolated mouse hearts underwent 35 min of global ischemia followed by 30 min of reperfusion with atorvastatin.
- Infarct size was assessed using triphenyltetrazolium chloride staining and the PI3K signaling cascade was analyzed by Western blot.
- The effectiveness of atorvastatin was measured across incremental doses from 25 to 100 micromol/l.
- Atorvastatin significantly reduced infarct size in a dose-dependent manner, achieving 16 +/- 2% at 50 micromol/l compared to 33 +/- 2% in controls (p < 0.01).
- Protection was diminished with PI3K inhibitor wortmannin and absent in eNOS knockout mice.
- Atorvastatin triggered rapid activation of the PI3K/Akt pathway, increasing Akt and eNOS phosphorylation by 4.1-fold and 2.9-fold, respectively (p < 0.01).
Structured PICO
Does atorvastatin reduce infarct size in isolated perfused mouse hearts subjected to ischemia and reperfusion?
P
Population
Isolated perfused mouse hearts (including wild-type and eNOS knockout mice) subjected to 35 min of global ischemia
I
Intervention
Atorvastatin (incremental concentrations 25 to 100 micromol/l) administered during reperfusion
C
Comparator
Control (no atorvastatin) and atorvastatin with wortmannin (PI3K inhibitor)
O
Outcome
Infarct size determined by triphenyltetrazolium chloride stainingsurrogate
Main Result
Absolute Event Rate: 16% vs 33%
p-value: p=<0.01
Atorvastatin administered at the onset of reperfusion limits myocardial infarct size through activation of the PI3K/Akt/eNOS pro-survival pathway, independent of its lipid-lowering effects.
Cite This Study
Bell et al. (2003) studied Myocardial ischemia/reperfusion injury. Atorvastatin vs. Control was evaluated on Infarct size (p=<0.01). Atorvastatin administered at reperfusion significantly reduced infarct size in isolated mouse hearts (16% vs 33%, p<0.01) via activation of the PI3K/Akt signaling cascade and eNOS.