HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Frank W. Sellke Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Laham, R. J. Articles by Sellke, F. W. Search for Related Content PubMed PubMed Citation Articles by Laham, R. J. Articles by Sellke, F. W.

J Thorac Cardiovasc Surg 1998;116:1022-1028
© 1998 Mosby, Inc.

CARDIOPULMONARY SUPPORT AND PHYSIOLOGY

MODULATION OF MYOCARDIAL PERFUSION AND VASCULAR REACTIVITY BY PERICARDIAL BASIC FIBROBLAST GROWTH FACTOR: INSIGHT INTO ISCHEMIA-INDUCED REDUCTION IN ENDOTHELIUM-DEPENDENT VASODILATATION

Supported in part by National Institutes of Health grants HL 53793 and HL 56993 (M.S.), MO1-RR01032 (R.J.L.), and HL 46716 (F.W.S.), and a grant from Chiron Corporation.

Read at the Seventy-eighth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 3-6, 1998.

Received for publication May 8, 1998. Revisions requested June 15, 1998; revisions received July 3, 1998. Accepted for publication Aug 20, 1998. Address for reprints: Frank W. Sellke, MD, Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA 02215.

Objectives:The present study was designed to study the effects of a single intrapericardial injection of basic fibroblast growth factor on myocardial vascular resistance and endothelium-dependent microvascular dilatation in a porcine model of chronic myocardial ischemia and to investigate the mechanism of ischemia-induced impairment of endothelium-dependent vasodilatation.
Methods: Yorkshire pigs underwent ameroid constrictor placement on the left circumflex coronary artery. At 3 weeks, animals were randomized to a single intrapericardial injection of saline solution (n = 10), 30 µg basic fibroblast growth factor (n = 10), or 2 mg basic fibroblast growth factor (n = 10). Myocardial vascular resistance in the normal (left anterior descending) and ischemic collateral-dependent (left circumflex artery) territories (using colored microspheres) and microvascular reactivity to adenosine diphosphate and sodium nitroprusside were measured before treatment and 4 weeks after treatment. The expression of inducible and endothelial nitric oxide synthase was determined in normal and ischemic myocardium by means of reverse transcriptase–polymerase chain reaction and Western analysis, and the effect of nitric oxide on endothelium-dependent vasodilatation was determined.
Results: Compared with results in the control group, treatment with basic fibroblast growth factor resulted in significant improvement in left circumflex artery resistance and endothelium-dependent vasodilatation, reflecting increased collaterals. Myocardial ischemia was associated with increased expression of inducible nitric oxide synthase with no change in endothelial nitric oxide synthase. However, the nitric oxide donor sodium nitroprusside did not affect endothelium-dependent vasodilatation to adenosine diphosphate.
Conclusions: A single intrapericardial bolus of basic fibroblast growth factor may be a useful therapeutic strategy for the treatment of myocardial ischemia in patients with coronary artery disease. Although chronic myocardial ischemia is associated with increased expression of inducible nitric oxide synthase, it does not appear to be the cause of altered endothelial function.

This article has been cited by other articles:

				J. A.I. Virag, M. L. Rolle, J. Reece, S. Hardouin, E. O. Feigl, and C. E. Murry Fibroblast Growth Factor-2 Regulates Myocardial Infarct Repair: Effects on Cell Proliferation, Scar Contraction, and Ventricular Function Am. J. Pathol., November 1, 2007; 171(5): 1431 - 1440. [Abstract] [Full Text] [PDF]

				S. Mieno, M. Boodhwani, R. T. Clements, B. Ramlawi, N. R. Sodha, J. Li, and F. W. Sellke Aging is associated with an impaired coronary microvascular response to vascular endothelial growth factor in patients J. Thorac. Cardiovasc. Surg., December 1, 2006; 132(6): 1348 - 1355. [Abstract] [Full Text] [PDF]

				K. L. Griffin, C. R. Woodman, E. M. Price, M. H. Laughlin, and J. L. Parker Endothelium-Mediated Relaxation of Porcine Collateral-Dependent Arterioles Is Improved by Exercise Training Circulation, September 18, 2001; 104(12): 1393 - 1398. [Abstract] [Full Text] [PDF]

				R. J. Laham, N. A. Chronos, M. Pike, M. E. Leimbach, J. E. Udelson, J. D. Pearlman, R. I. Pettigrew, M. J. Whitehouse, C. Yoshizawa, and M. Simons Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: results of a Phase I open-label dose escalation study J. Am. Coll. Cardiol., December 1, 2000; 36(7): 2132 - 2139. [Abstract] [Full Text] [PDF]

				J. E. Udelson, V. Dilsizian, R. J. Laham, N. Chronos, J. Vansant, M. Blais, J. R. Galt, M. Pike, C. Yoshizawa, and M. Simons Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease Circulation, October 3, 2000; 102(14): 1605 - 1610. [Abstract] [Full Text] [PDF]

				E. Sosa, M. Scanavacca, A. d’Avila, R. L. Verrier, S. Waxman, E. G. Lovett, and R. Moreno Different Ways of Aproaching the Normal Pericardial Space • Response Circulation, December 14, 1999; 100 (24): e115 - e116. [Full Text] [PDF]