What question did this study set out to answer?

To evaluate whether combining granulocyte colony-stimulating factor (G-CSF) with myelosuppressive agents improves stem cell mobilization and myocardial repair after myocardial infarction.

January 1, 2007Circulation JournalOpen Access

Modification of Post-Myocardial Infarction Granulocyte-Colony Stimulating Factor Therapy With Myelosuppressives

Q: What is the clinical evidence from this study?

Population: Myocardial Infarction (n=160). Intervention: G-CSF combined with myelosuppressives (5-fluorouracil and cyclophosphamide) vs. Saline, G-CSF alone, or myelosuppressives alone. Primary outcome: Left ventricular ejection fraction and end-diastolic dimension at 28 days post-MI (p=<0.05).

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Key result

The combination of G-CSF and myelosuppressives significantly improved left ventricular ejection fraction, reduced left ventricular remodeling, and enhanced myocardial repair compared to G-CSF alone or saline in a rabbit model of myocardial infarction.

Why the study?

Does the combination of G-CSF and myelosuppressives improve myocardial repair and cardiac function in a rabbit model of post-myocardial infarction?

Key Points

To evaluate whether combining granulocyte colony-stimulating factor (G-CSF) with myelosuppressive agents improves stem cell mobilization and myocardial repair after myocardial infarction.
Rabbits underwent 30 minutes of myocardial ischemia followed by reperfusion.
Twenty-four hours post-reperfusion, animals were assigned to four treatment arms: myelosuppressives alone, G-CSF alone, combined myelosuppressives and G-CSF, or saline control.
The role of the CXCR4/SDF-1 axis was evaluated using the specific CXCR4 antagonist AMD3100.
The combination regimen yielded significantly higher numbers of circulating stem cells and greater myocardial SDF-1 expression than G-CSF alone, while attenuating leukocytosis.
Combined therapy enhanced bone marrow-derived cardiomyocyte and endothelial cell recruitment, reduced scar size, improved cardiac function, and reduced chronic left ventricular remodeling.
Coadministration of AMD3100 completely abolished the functional and structural benefits conferred by the combined therapy.

Structured PICO

Does the combination of G-CSF and myelosuppressives improve myocardial repair and cardiac function in a rabbit model of post-myocardial infarction?

Population

160 male Japanese white rabbits subjected to a 30-minute ischemia-reperfusion myocardial infarction model, followed for up to 28 days.

Intervention

Combination of myelosuppressives (5-fluorouracil 5 mg/kg/day and cyclophosphamide 20 mg/kg/day intravenously on days 1 and 2) and granulocyte colony-stimulating factor (G-CSF 10 μg/kg/day subcutaneously on days 3 to 7)

Comparator

Saline, myelosuppressives alone, or G-CSF alone

Outcome

Myocardial repair, cardiac function (LVEF, LVEDD), and left ventricular remodeling at 28 days post-myocardial infarctionsurrogate

Main Result

p-value: p=<0.05

The combination of G-CSF and myelosuppressives synergistically improves post-MI cardiac function and reduces remodeling in a rabbit model by enhancing stem cell recruitment via the CXCR4/SDF-1 axis.

Limitations

It is still unclear whether the new myocytes and endothelial cells were formed by cell differentiation or by cell fusion.
Myelosuppressives such as 5-fluorouracil and cyclophosphamide are potentially cardiotoxic in the clinical setting.
Unclear whether the new myocytes and endothelial cells were formed by cell differentiation or by cell fusion

Discussion

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Implication

Should not alter practice; leaves open translation of G-CSF combinations to human post-MI trials.

Cite This Study

Misao et al. (2007) studied Myocardial Infarction (n=160). G-CSF combined with myelosuppressives (5-fluorouracil and cyclophosphamide) vs. Saline, G-CSF alone, or myelosuppressives alone was evaluated on Left ventricular ejection fraction and end-diastolic dimension at 28 days post-MI (p=<0.05). The combination of G-CSF and myelosuppressives significantly improved left ventricular ejection fraction, reduced left ventricular remodeling, and enhanced myocardial repair compared to G-CSF alone or saline in a rabbit model of myocardial infarction.

synapsesocial.com/papers/6a95ce59db04510482c5d6e9 https://doi.org/10.1253/circj.71.580

Topics

Echocardiography

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Modification of Post-Myocardial Infarction Granulocyte-Colony Stimulating Factor Therapy With Myelosuppressives

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Topics

Modification of Post-Myocardial Infarction Granulocyte-Colony Stimulating Factor Therapy With Myelosuppressives

Key Points

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Also Consider

Topics

Also Consider