September 28, 2010Journal of Cardiovascular Pharmacology
Pharmacologic Inhibition of Phosphoinositide 3-Kinase Gamma (PI3Kγ) Promotes Infarct Resorption and Prevents Adverse Cardiac Remodeling After Myocardial Infarction in Mice
Key result
Pharmacologic inhibition of PI3Kγ with AS-605240 significantly reduced infarct size at 4 weeks compared to vehicle (14% vs 28%, P<0.001) and improved cardiac remodeling in mice after AMI.
Why the study?
Does pharmacologic inhibition of PI3Kγ with AS-605240 improve infarct resorption and prevent adverse cardiac remodeling in mice after experimental AMI?
Population
CD-1 male mice after experimental acute myocardial infarction induced by surgical coronary artery ligation
Comparison
AS-605240 for 14 days vs Vehicle for 14 days
Design
Preclinical, randomly assigned
Follow-up
4 weeks
Authors
Discussion
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Implication
Hypothesis-generating for PI3Kγ inhibition after AMI; human trials needed before clinical translation.
Study Design
Type
RCT
Randomization
randomly assigned
Structured PICO
Does pharmacologic inhibition of PI3Kγ with AS-605240 improve infarct resorption and prevent adverse cardiac remodeling in mice after experimental AMI?
P
Population
CD-1 male mice with experimental acute myocardial infarction followed for 4 weeks.
I
Intervention
AS-605240 (10 mg/kg/day intraperitoneally) for 14 days
C
Comparator
Vehicle (NaCl 0.9% + DMSO 25% solution) for 14 days
O
Outcome
Left ventricular dimensions and function, and infarct size measured at 1, 7, 14, and 28 dayssurrogate
Main Result
Absolute Event Rate: 14% vs 28%
p-value: p=<0.001
Pharmacologic inhibition of PI3Kγ with AS-605240 in a mouse model of AMI reduces infarct size and prevents adverse cardiac remodeling.
Cite This Study
Seropián et al. (2010) conducted an RCT in Acute myocardial infarction. AS-605240 vs. Vehicle (NaCl 0.9% + DMSO 25% solution) was evaluated on Infarct size at 4 weeks after AMI (p=<0.001). Pharmacologic inhibition of PI3Kγ with AS-605240 significantly reduced infarct size at 4 weeks compared to vehicle (14% vs 28%, P<0.001) and improved cardiac remodeling in mice after AMI.