Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: A comparative study

Shankha S. Biswas, G. Chad Hughes, John E. Scarborough, Patrick W. Domkowski, Luis Diodato, Monica L. Smith, Carolyn Landolfo, James E. Lowe, Brian H. Annex, Kevin P. Landolfo

Research output: Contribution to journalArticle

Abstract

Objective: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months (P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months (P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.

Original languageEnglish (US)
Pages (from-to)34-43
Number of pages10
JournalJournal of Thoracic and Cardiovascular Surgery
Volume127
Issue number1
DOIs
StatePublished - Jan 2004
Externally publishedYes

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Fibroblast Growth Factor 2
Myocardium
Swine
Stress Echocardiography
Arteries
Positron-Emission Tomography
Coronary Artery Disease
Injections
Regional Blood Flow
Coronary Vessels
Pathologic Constriction
Ischemia
Perfusion

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Biswas, S. S., Hughes, G. C., Scarborough, J. E., Domkowski, P. W., Diodato, L., Smith, M. L., ... Landolfo, K. P. (2004). Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: A comparative study. Journal of Thoracic and Cardiovascular Surgery, 127(1), 34-43. https://doi.org/10.1016/j.jtcvs.2003.07.003

Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium : A comparative study. / Biswas, Shankha S.; Hughes, G. Chad; Scarborough, John E.; Domkowski, Patrick W.; Diodato, Luis; Smith, Monica L.; Landolfo, Carolyn; Lowe, James E.; Annex, Brian H.; Landolfo, Kevin P.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 127, No. 1, 01.2004, p. 34-43.

Research output: Contribution to journalArticle

Biswas, SS, Hughes, GC, Scarborough, JE, Domkowski, PW, Diodato, L, Smith, ML, Landolfo, C, Lowe, JE, Annex, BH & Landolfo, KP 2004, 'Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium: A comparative study', Journal of Thoracic and Cardiovascular Surgery, vol. 127, no. 1, pp. 34-43. https://doi.org/10.1016/j.jtcvs.2003.07.003
Biswas, Shankha S. ; Hughes, G. Chad ; Scarborough, John E. ; Domkowski, Patrick W. ; Diodato, Luis ; Smith, Monica L. ; Landolfo, Carolyn ; Lowe, James E. ; Annex, Brian H. ; Landolfo, Kevin P. / Intramyocardial and intracoronary basic fibroblast growth factor in porcine hibernating myocardium : A comparative study. In: Journal of Thoracic and Cardiovascular Surgery. 2004 ; Vol. 127, No. 1. pp. 34-43.
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abstract = "Objective: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods: Twenty-four mini-swine with 90{\%} left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months (P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months (P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.",
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T2 - A comparative study

AU - Biswas, Shankha S.

AU - Hughes, G. Chad

AU - Scarborough, John E.

AU - Domkowski, Patrick W.

AU - Diodato, Luis

AU - Smith, Monica L.

AU - Landolfo, Carolyn

AU - Lowe, James E.

AU - Annex, Brian H.

AU - Landolfo, Kevin P.

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N2 - Objective: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months (P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months (P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.

AB - Objective: Therapeutic angiogenesis is an alternative method of revascularization for end-stage coronary artery disease. We determined the effects of intramyocardial and intracoronary basic fibroblast growth factor 2 on myocardial blood flow and function in a porcine model of hibernating myocardium. Methods: Twenty-four mini-swine with 90% left circumflex artery stenosis and documented hibernating myocardium by positron emission tomography and dobutamine stress echocardiography were randomized to intramyocardial basic fibroblast growth factor 2 at 0.6 μg/kg (mid-dose, n = 6, 30 injections/animal), 6 μg/kg (high-dose, n = 6, 30 injections/animal), or intramyocardial vehicle control (n = 6). The intracoronary group received 6 μg/kg basic fibroblast growth factor 2 (n = 6) into the right and left circumflex artery coronary arteries. Positron emission tomography and dobutamine stress echocardiography were repeated at 1 and 3 months. Results: In the vehicle group, normalized left circumflex artery myocardial blood flow was 0.74 ± 0.04 at 1 month and 0.75 ± 0.07 at 3 months compared with 0.68 ± 0.03 at baseline. In the intracoronary group, myocardial blood flow was 0.71 ± 0.03 at 1 month and 0.72 ± 0.04 at 3 months compared with 0.67 ± 0.04 at baseline. In the mid group, myocardial blood flow was 0.73 ± 0.06 at 1 month and 0.85 ± 0.05 at 3 months (P < .001) compared with 0.67 ± 0.04 at baseline. In the high group, myocardial blood flow was 0.81 ± 0.06 at 1 month and 0.83 ± .04 at 3 months (P = .03) compared with 0.71 ± 0.02 at baseline. No significant improvements in ischemia were demonstrated in any of the groups by dobutamine stress echocardiography at 1 or 3 months. Conclusions: In porcine hibernating myocardium, intramyocardial basic fibroblast growth factor 2 significantly improved regional myocardial blood flow 3 months after treatment. There was no significant change in function in any of the 4 groups. These data suggest that intramyocardial dosing of basic fibroblast growth factor 2 (0.6 μg/kg) may be an optimal dose for improving perfusion in the treatment of end-stage coronary artery disease.

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