Combination of enoxaparin and fibroblast growth factor-1 increases myocardial blood flow and capillary density after myocardial infarction in rabbits

被引:6
作者
Geist, A
Marx, J
Müller, S
Uzan, A
von Specht, BU
Haberstroh, J
机构
[1] Univ Hosp Freiburg, Dept Surg Res, DE-79106 Freiburg, Germany
[2] Avenis Pharma, Paris, France
关键词
fibroblast growth factor; enoxaparin; angiogenesis; myocardial infarction; rabbit model;
D O I
10.1159/000087862
中图分类号
R61 [外科手术学];
学科分类号
摘要
Objective: The effect of enoxaparin and fibroblast growth factor-1 (FGF-1) on post-infarction capillary density and regional myocardial blood flow (RMBF) was examined. Methods: New Zealand White rabbits received an intra-myocardial injection of either physiological saline, FGF-1 + enoxaparin, FGF-1 or enoxaparin directly after ligation of the left anterior descending artery. RMBF and capillary density were investigated using fluorescent microspheres and histological examination. Results: One week after infarction a significant difference in the number of capillaries could be demonstrated within the FGF-1 + enoxaparin group (p < 0.001 versus the control group), the FGF-1 group (p < 0.01) and the enoxaparin group (p < 0.05). Treatment with FGF-1 + enoxaparin resulted in a significantly increased number of capillaries compared to treatment with FGF-1 (p < 0.05) and enoxaparin (p < 0.05) alone. Additionally, all groups treated with FGF-1 and/or enoxaparin showed a significant increase of microvessel density in the treated ischemic border zone compared to the non-treated ischemic border zone (p < 0.001 for FGF-1 + enoxaparin, p < 0.01 for FGF-1, p < 0.05 for enoxaparin). RMBF was significantly increased within the FGF-1 + enoxaparin group compared to the control group (p < 0.05). Moreover, perfusion rates within the FGF-1 + enoxaparin-treated area did not significantly differ from the pre-infarction values. Conclusion: Treatment with either enoxaparin or FGF-1 or FGF-1 + enoxaparin resulted in increased microvessel growth. However, only the combination of enoxaparin with FGF-1 promotes capillary growth and RMBF. Thus, we conclude that enoxaparin enhances the angiogenic potential of intramyocardially injected FGF-1 in the acutely infarcted rabbit heart. Copyright (C) 2005 S. Karger AG, Basel.
引用
收藏
页码:191 / 198
页数:8
相关论文
共 29 条
[1]   Enoxaparin as adjunctive antithrombin therapy for ST-elevation myocardial infarction - Results of the ENTIRE-thrombolysis in myocardial infarction (TIMI) 23 trial [J].
Antman, EM ;
Louwerenburg, HW ;
Baars, HF ;
Wesdorp, JCL ;
Hamer, B ;
Bassand, JP ;
Bigonzi, F ;
Pisapia, G ;
Gibson, CM ;
Heidbuchel, H ;
Braunwald, E ;
Van de Werf, F .
CIRCULATION, 2002, 105 (14) :1642-1649
[2]   HEPARIN-DERIVED OLIGOSACCHARIDES - AFFINITY FOR ACIDIC FIBROBLAST GROWTH-FACTOR AND EFFECT ON ITS GROWTH-PROMOTING ACTIVITY FOR HUMAN-ENDOTHELIAL CELLS [J].
BARZU, T ;
LORMEAU, JC ;
PETITOU, M ;
MICHELSON, S ;
CHOAY, J .
JOURNAL OF CELLULAR PHYSIOLOGY, 1989, 140 (03) :538-548
[3]   HEPARIN ACCELERATES CORONARY COLLATERAL DEVELOPMENT IN A PORCINE MODEL OF CORONARY-ARTERY OCCLUSION [J].
CARROLL, SM ;
WHITE, FC ;
ROTH, DM ;
BLOOR, CM .
CIRCULATION, 1993, 88 (01) :198-207
[4]   Low-molecular-weight heparins in non-ST-segment elevation ischemia: The ESSENCE trial [J].
Cohen, M ;
Demers, C ;
Gurfinkel, EP ;
Turpie, AGG ;
Fromell, GJ ;
Goodman, S ;
Langer, A ;
Califf, RM ;
Fox, KAA ;
Premmereur, J ;
Bigonzi, F .
AMERICAN JOURNAL OF CARDIOLOGY, 1998, 82 (5B) :19L-24L
[5]   Randomized double-blind safety study of enoxaparin versus unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes treated with tirofiban and aspirin:: The ACUTE II study [J].
Cohen, M ;
Théroux, P ;
Borzak, S ;
Frey, MJ ;
White, HD ;
Van Mieghem, W ;
Senatore, F ;
Lis, J ;
Mukherjee, R ;
Harris, K ;
Bigonzi, F .
AMERICAN HEART JOURNAL, 2002, 144 (03) :470-477
[6]   Structure of a heparin-linked biologically active dimer of fibroblast growth factor [J].
DiGabriele, AD ;
Lax, I ;
Chen, DI ;
Svahn, CM ;
Jaye, M ;
Schlessinger, J ;
Hendrickson, WA .
NATURE, 1998, 393 (6687) :812-817
[7]   Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without St elevation: a meta-analysis [J].
Eikelboom, JW ;
Anand, SS ;
Malmberg, K ;
Weitz, JI ;
Ginsberg, JS ;
Yusuf, S .
LANCET, 2000, 355 (9219) :1936-1942
[8]   PROSPECTIVE, RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND, MULTICENTER STUDY OF EXERCISE WITH ENOXAPARIN PRETREATMENT FOR STABLE-EFFORT ANGINA [J].
FUJITA, M ;
SASAYAMA, S ;
KATO, K ;
TAKAORI, S ;
ONODERA, K ;
MIKUNIYA, A ;
AIZAWA, T ;
KIRIGAYA, H ;
SUZUKI, S ;
KITAHARA, K ;
OGAWA, T ;
NAKAGOMI, A ;
NAKAMURA, Y ;
OGAWA, S ;
AKAISHI, M ;
HOSODA, S ;
IWADE, K ;
MOTOMIYA, T ;
TEJIMA, T ;
JIMBO, M ;
TAKEDA, R ;
SHIMIZU, M ;
TAKEGOSHI, R ;
KANEMITSU, S ;
EJIRI, M ;
NAKAMURA, T ;
LEE, JD ;
TAKAHASHI, M ;
NAKANO, T ;
YAMAKADO, T ;
KINOSHITA, M ;
YAMADA, T ;
KODAMA, K ;
HIRAYAMA, A ;
SATO, H ;
YOSHIMURA, M .
AMERICAN HEART JOURNAL, 1995, 129 (03) :535-541
[9]   HEPARIN PROTECTS BASIC AND ACIDIC FGF FROM INACTIVATION [J].
GOSPODAROWICZ, D ;
CHENG, J .
JOURNAL OF CELLULAR PHYSIOLOGY, 1986, 128 (03) :475-484
[10]  
HAMMERLE H, 1991, VASA-J VASCULAR DIS, V20, P207