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Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing.
Catheter Cardiovasc Interv. 2007 Feb 01; 69(2):257-66.CC

Abstract

BACKGROUND

Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion.

METHODS

MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days.

RESULTS

At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar.

CONCLUSIONS

Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials.

Authors+Show Affiliations

Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. n-beohar@northwestern.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17253607

Citation

Beohar, Nirat, et al. "Granulocyte-colony Stimulating Factor Administration After Myocardial Infarction in a Porcine Ischemia-reperfusion Model: Functional and Pathological Effects of Dose Timing." Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions, vol. 69, no. 2, 2007, pp. 257-66.
Beohar N, Flaherty JD, Davidson CJ, et al. Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing. Catheter Cardiovasc Interv. 2007;69(2):257-66.
Beohar, N., Flaherty, J. D., Davidson, C. J., Vidovich, M., Singhal, S., Rapp, J. A., Erdogan, A., Lee, D. C., Rammohan, C., Brodsky, A., Wu, E., Pieper, K., Virmani, R., Bonow, R. O., & Mehta, J. (2007). Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing. Catheterization and Cardiovascular Interventions : Official Journal of the Society for Cardiac Angiography & Interventions, 69(2), 257-66.
Beohar N, et al. Granulocyte-colony Stimulating Factor Administration After Myocardial Infarction in a Porcine Ischemia-reperfusion Model: Functional and Pathological Effects of Dose Timing. Catheter Cardiovasc Interv. 2007 Feb 1;69(2):257-66. PubMed PMID: 17253607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Granulocyte-colony stimulating factor administration after myocardial infarction in a porcine ischemia-reperfusion model: functional and pathological effects of dose timing. AU - Beohar,Nirat, AU - Flaherty,James D, AU - Davidson,Charles J, AU - Vidovich,Mladen, AU - Singhal,Seema, AU - Rapp,Jonathan A, AU - Erdogan,Ata, AU - Lee,Daniel C, AU - Rammohan,Chidambaram, AU - Brodsky,Adam, AU - Wu,Edwin, AU - Pieper,Karen, AU - Virmani,Renu, AU - Bonow,Robert O, AU - Mehta,Jayesh, PY - 2007/1/27/pubmed PY - 2007/4/4/medline PY - 2007/1/27/entrez SP - 257 EP - 66 JF - Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions JO - Catheter Cardiovasc Interv VL - 69 IS - 2 N2 - BACKGROUND: Acute MI results in cardiomyocyte death, left ventricular (LV) dysfunction and adverse remodeling. The use of growth factors may prevent this. The aim of this study was to assess early and delayed administration of granulocyte colony-stimulating factor (G-CSF) in a porcine model of myocardial infarction (MI) and reperfusion. METHODS: MI was induced by balloon occlusion followed by reperfusion. There were 3 groups: Control (n = 11), Early (n = 17), and Delayed treatment (n = 8). The Early group received G-CSF 10 microg/kg/d every other day for 20 days beginning immediately. The Delayed group received G-CSF 10 microg/kg/d daily for 10 days beginning on day 5. Magnetic resonance imaging was performed on days 5 and 56. LV end-diastolic volumes (EDV), end-systolic volumes, ejection fraction, expansion index, sphericity index, thinning ratio, and infarct mass were calculated. Histology was analyzed at 56 days. RESULTS: At 56 days the change in EDV was 53% less in the Early (p = 0.005) and 24% greater in the Delayed (p = NS) group versus Control. The Delayed group also showed a 60% increase in normalized infarct mass (p = 0.055) and an 88% increase in expansion index (p = 0.003). Both groups had significantly less capillary density in the infarct border zone. The Delayed also had decreased arteriolar density in the mid scar. CONCLUSIONS: Early treatment with G-CSF after MI decreases ventricular dilatation, while delayed treatment has a deleterious effect on LV remodeling. This may be related to changes in myocardial vascularity. The effects of G-CSF therapy and its dose timing help to elucidate the results of recent human trials. SN - 1522-1946 UR - https://www.unboundmedicine.com/medline/citation/17253607/Granulocyte_colony_stimulating_factor_administration_after_myocardial_infarction_in_a_porcine_ischemia_reperfusion_model:_functional_and_pathological_effects_of_dose_timing_ L2 - https://doi.org/10.1002/ccd.20925 DB - PRIME DP - Unbound Medicine ER -