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Phenytoin can accelerate the healing process after experimental myocardial infarction?
Int J Cardiol. 2006 Feb 08; 107(1):21-9.IJ

Abstract

BACKGROUND

Over-degradation and/or inadequate accumulation of extracellular matrix after myocardial infarction (MI) may lead to adverse ventricular remodeling, even ventricular aneurysm or rupture. Phenytoin can increase gingival overgrowth by stimulating the proliferation of connective tissue, which implies a novel way to hasten the healing process after MI.

METHODS

Experimental MI was induced by permanent coronary ligation. Surviving rats after MI were randomly divided into phenytoin, captopril, phenytoin plus captopril, operation control and sham operation group. Picrosirius red staining plus polarized microscopy was used for collagen analysis. Left ventricular passive pressure-volume relationship was determined ex vivo. The effects of phenytoin concentration gradient (0, 1.25, 2.5, 5.0, 10.0, and 20.0 microg/mL) on transforming growth factor-beta1 (TGF-beta1) mRNA and protein expression by neonatal rat cardiac fibroblast were determined using semi-quantitative RT-PCR and ELISA, respectively. Peritoneal macrophage was incubated with same gradient of phenytoin concentration. Then the supernatant was harvested to stimulate another 6 groups of cardiac fibroblast, to investigate possible role mediated by macrophage.

RESULTS

Phenytoin treatment could promote type I collagen cross-linking level and ratio of type I/III collagen in the infarcted region and had no obvious side effect on interstitial collagen volume fraction, subtype ratio and distribution in non-infarcted region. Phenytoin-treated hearts exhibited attenuation of global ventricular dilation. Phenytoin alone had no direct effects on rat cardiac fibroblast proliferation and collagen production in vitro, but phenytoin-stimulated macrophage could exert a positive influence on cardiac fibroblast TGF-beta1 mRNA and protein production, which exhibited a dose-dependent manner.

CONCLUSIONS

Phenytoin can accelerate the healing process in the infarcted region and has no obviously detrimental influence on collagen accumulation in non-infarcted region, which implies a potential benefit to patients undergoing early post-infarction ventricular remodeling process.

Authors+Show Affiliations

Institute of Cardiovascular Disease, Pingjin Hospital, Medical College of Armed Police Forces, Cheng-lin-zhuang Street, Hedong District, Tianjin, 300162, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15996772

Citation

Zhou, Xin, et al. "Phenytoin Can Accelerate the Healing Process After Experimental Myocardial Infarction?" International Journal of Cardiology, vol. 107, no. 1, 2006, pp. 21-9.
Zhou X, Li YM, Ji WJ, et al. Phenytoin can accelerate the healing process after experimental myocardial infarction? Int J Cardiol. 2006;107(1):21-9.
Zhou, X., Li, Y. M., Ji, W. J., Jiang, T. M., Sun, X. N., Zhu, Y., & Shi, R. (2006). Phenytoin can accelerate the healing process after experimental myocardial infarction? International Journal of Cardiology, 107(1), 21-9.
Zhou X, et al. Phenytoin Can Accelerate the Healing Process After Experimental Myocardial Infarction. Int J Cardiol. 2006 Feb 8;107(1):21-9. PubMed PMID: 15996772.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenytoin can accelerate the healing process after experimental myocardial infarction? AU - Zhou,Xin, AU - Li,Yu-Ming, AU - Ji,Wen-Jie, AU - Jiang,Tie-Min, AU - Sun,Xiao-Nan, AU - Zhu,Yong, AU - Shi,Rui, Y1 - 2005/07/05/ PY - 2004/08/24/received PY - 2004/12/11/revised PY - 2004/12/30/accepted PY - 2005/7/6/pubmed PY - 2006/4/14/medline PY - 2005/7/6/entrez SP - 21 EP - 9 JF - International journal of cardiology JO - Int J Cardiol VL - 107 IS - 1 N2 - BACKGROUND: Over-degradation and/or inadequate accumulation of extracellular matrix after myocardial infarction (MI) may lead to adverse ventricular remodeling, even ventricular aneurysm or rupture. Phenytoin can increase gingival overgrowth by stimulating the proliferation of connective tissue, which implies a novel way to hasten the healing process after MI. METHODS: Experimental MI was induced by permanent coronary ligation. Surviving rats after MI were randomly divided into phenytoin, captopril, phenytoin plus captopril, operation control and sham operation group. Picrosirius red staining plus polarized microscopy was used for collagen analysis. Left ventricular passive pressure-volume relationship was determined ex vivo. The effects of phenytoin concentration gradient (0, 1.25, 2.5, 5.0, 10.0, and 20.0 microg/mL) on transforming growth factor-beta1 (TGF-beta1) mRNA and protein expression by neonatal rat cardiac fibroblast were determined using semi-quantitative RT-PCR and ELISA, respectively. Peritoneal macrophage was incubated with same gradient of phenytoin concentration. Then the supernatant was harvested to stimulate another 6 groups of cardiac fibroblast, to investigate possible role mediated by macrophage. RESULTS: Phenytoin treatment could promote type I collagen cross-linking level and ratio of type I/III collagen in the infarcted region and had no obvious side effect on interstitial collagen volume fraction, subtype ratio and distribution in non-infarcted region. Phenytoin-treated hearts exhibited attenuation of global ventricular dilation. Phenytoin alone had no direct effects on rat cardiac fibroblast proliferation and collagen production in vitro, but phenytoin-stimulated macrophage could exert a positive influence on cardiac fibroblast TGF-beta1 mRNA and protein production, which exhibited a dose-dependent manner. CONCLUSIONS: Phenytoin can accelerate the healing process in the infarcted region and has no obviously detrimental influence on collagen accumulation in non-infarcted region, which implies a potential benefit to patients undergoing early post-infarction ventricular remodeling process. SN - 0167-5273 UR - https://www.unboundmedicine.com/medline/citation/15996772/Phenytoin_can_accelerate_the_healing_process_after_experimental_myocardial_infarction L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-5273(05)00520-6 DB - PRIME DP - Unbound Medicine ER -