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Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.

Publication ,  Journal Article
Lazarous, DF; Scheinowitz, M; Shou, M; Hodge, E; Rajanayagam, S; Hunsberger, S; Robison, WG; Stiber, JA; Correa, R; Epstein, SE
Published in: Circulation
January 1, 1995

BACKGROUND: Recently we reported that intracoronary administration of basic fibroblast growth factor (bFGF), a potent angiogenic peptide, increases collateral blood flow in dogs subjected to progressive left circumflex coronary artery (LCx) occlusion. The aim of the present study was to examine the effect of systemically administered bFGF on collateral blood flow and to assess its pharmacokinetics and potential side effects. METHODS AND RESULTS: Forty-seven dogs were subjected to progressive ameroid-induced occlusion of the LCx, an intervention known to induce the development of collateral vessels. In phase I of the investigation, dogs were randomized to receive bFGF 1.74 mg/d (n = 10) or saline (n = 9) as a left atrial injection for 4 weeks. Relative collateral blood flow was assessed serially with radiolabeled microspheres in the conscious state during maximal coronary vasodilatation. Initiation of bFGF treatment was temporally associated with a marked acceleration of collateral development; however, collateral flow in control dogs improved toward the end of the study, approaching that of bFGF-treated dogs at the 38-day end point. Phase II of the investigation was a three-armed study of extended duration to determine whether bFGF caused a sustained increase in collateral function. Dogs were randomized to receive bFGF 1.74 mg/d for 9 weeks (n = 7), bFGF 1.74 mg/d for 5 weeks followed by placebo for 4 weeks (n = 11), or placebo for 9 weeks (n = 10). Relative and absolute collateral blood flow were assessed serially with microspheres during maximal coronary vasodilatation. Between the 10th and 17th days after ameroid placement, bFGF-treated dogs exhibited marked improvement in collateral flow such that maximal collateral conductance exceeded that of controls by 24% at the 5-week crossover point. Final collateral conductance was similar in dogs receiving bFGF for 5 and 9 weeks despite withdrawal of treatment in the former group. bFGF administration was associated with a 21% increase in final collateral conductance as well as a 49% increase in collateral zone vascular density. Prolonged bFGF administration was also associated with a decrease in arterial pressure, moderate thrombocytopenia, and moderate, reversible anemia. CONCLUSIONS: Systemic administration of bFGF enhanced collateral conductance in dogs with progressive single-vessel coronary occlusion. The beneficial effect of bFGF occurred primarily between the 7th and 14th days of therapy, and regression of collateral development was not noted after withdrawal of treatment. The present investigation provides impetus to the concept that collateral development can be enhanced pharmacologically-specifically by bFGF-raising the possibility that such an intervention might eventually be applied clinically.

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Published In

Circulation

DOI

ISSN

0009-7322

Publication Date

January 1, 1995

Volume

91

Issue

1

Start / End Page

145 / 153

Location

United States

Related Subject Headings

  • Myocardial Infarction
  • Hemodynamics
  • Hematocrit
  • Fibroblast Growth Factor 2
  • Drug Administration Schedule
  • Dogs
  • Coronary Disease
  • Collateral Circulation
  • Cardiovascular System & Hematology
  • Animals
 

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Lazarous, D. F., Scheinowitz, M., Shou, M., Hodge, E., Rajanayagam, S., Hunsberger, S., … Epstein, S. E. (1995). Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation, 91(1), 145–153. https://doi.org/10.1161/01.cir.91.1.145
Lazarous, D. F., M. Scheinowitz, M. Shou, E. Hodge, S. Rajanayagam, S. Hunsberger, W. G. Robison, J. A. Stiber, R. Correa, and S. E. Epstein. “Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.Circulation 91, no. 1 (January 1, 1995): 145–53. https://doi.org/10.1161/01.cir.91.1.145.
Lazarous DF, Scheinowitz M, Shou M, Hodge E, Rajanayagam S, Hunsberger S, et al. Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation. 1995 Jan 1;91(1):145–53.
Lazarous, D. F., et al. “Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart.Circulation, vol. 91, no. 1, Jan. 1995, pp. 145–53. Pubmed, doi:10.1161/01.cir.91.1.145.
Lazarous DF, Scheinowitz M, Shou M, Hodge E, Rajanayagam S, Hunsberger S, Robison WG, Stiber JA, Correa R, Epstein SE. Effects of chronic systemic administration of basic fibroblast growth factor on collateral development in the canine heart. Circulation. 1995 Jan 1;91(1):145–153.

Published In

Circulation

DOI

ISSN

0009-7322

Publication Date

January 1, 1995

Volume

91

Issue

1

Start / End Page

145 / 153

Location

United States

Related Subject Headings

  • Myocardial Infarction
  • Hemodynamics
  • Hematocrit
  • Fibroblast Growth Factor 2
  • Drug Administration Schedule
  • Dogs
  • Coronary Disease
  • Collateral Circulation
  • Cardiovascular System & Hematology
  • Animals