Efficacy of intracoronary versus intravenous FGF-2 in a pig model of chronic myocardial ischemia

Sato, Kaori; Laham, Roger J.; Pearlman, Justin D.; Novicki, Deborah L.; Sellke, Frank W.; Simons, Michael; Post, Mark J.

doi:10.1016/s0003-4975(00)02018-x

Cited by 78 publications

(43 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In contrast to the brilliant results obtained by this formulation in various animal models of acute or progressive ischemia, 17 intracoronary protein administration in patients was not effective. Most likely, this negative result stemmed from a combination of reasons, including the very short, half-life of VEGF-A in vivo, insufficient myocardial uptake after coronary infusion and de-sensitization of chronically ischemic tissues to growth factor treatment.…”

Section: Clinical Use Of Vegfcontrasting

confidence: 68%

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

2012

View full text Add to dashboard Cite

Section: Clinical Use Of Vegfcontrasting

confidence: 68%

VEGF gene therapy: therapeutic angiogenesis in the clinic and beyond

2012

View full text Add to dashboard Cite

“…In a preclinical study, a single intracoronary injection of FGF2 improved perfusion and function 15 despite the initial (1 hour) retention of Ͻ1% of the total dose in the myocardium and a rapid washout of the retained protein. 16 Although these small amounts of retained FGF2 are effective in healthy, young animals, they may be insufficient in older patients with diffuse atherosclerotic disease.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Treatment of Coronary Artery Disease With Recombinant Fibroblast Growth Factor-2

et al. 2002

Self Cite

View full text Add to dashboard Cite

Background-Single-bolus intracoronary administration of fibroblast growth factor-2 (FGF2) improved symptoms and myocardial function in a phase I, open-label trial in patients with coronary artery disease. We conducted the FGF Initiating RevaScularization Trial (FIRST) to evaluate further the efficacy and safety of recombinant FGF2 (rFGF2). Methods and Results-FIRST is a multicenter, randomized, double-blind, placebo-controlled trial of a single intracoronary infusion of rFGF2 at 0, 0.3, 3, or 30 g/kg (nϭ337 patients). Efficacy was evaluated at 90 and 180 days by exercise tolerance test, myocardial nuclear perfusion imaging, Seattle Angina Questionnaire, and Short-Form 36 questionnaire. Exercise tolerance was increased at 90 days in all groups and was not significantly different between placebo and FGF-treated groups. rFGF2 reduced angina symptoms as measured by the angina frequency score of the Seattle Angina Questionnaire (overall Pϭ0.035) and the physical component summary scale of the Short-Form 36 (pairwise Pϭ0.033, all FGF groups versus placebo). These differences were more pronounced in highly symptomatic patients (baseline angina frequency score Յ40 or Canadian Cardiovascular Society score of III or IV). None of the differences were significant at 180 days because of continued improvement in the placebo group. Adverse events were similar across all groups, except for hypotension, which occurred with higher frequency in the 30-g/kg rFGF2 group.

show abstract

“…The lack of any clinical benefit in exercise tolerance was likely due to poor uptake of these protein factors from the coronary circulation and their short half-life, and thus, limited duration of activity of protein therapy. 7,8 Delivery of these proteins was also associated with dose-related toxicities resulting from systemic exposure, thus limiting the amount of growth factor that could be safely administered.…”

Section: Discussionmentioning

confidence: 99%

“…For instance, the early trials used intracoronary or intravenous injection of protein factors, and poor cardiac uptake and limited stability of these growth factors within the myocardium may have contributed to the lack of significant biological activity. 7,8 Similarly, randomized gene therapy trials have either lacked efficient transfection strategies or again relied on intracoronary delivery despite concerns from preclinical studies about the ability of this delivery strategy to effectively transduce the myocardium. 9 AdVEGF121, a replication-deficient adenoviral vector carrying the transgene encoding for VEGF121, has been shown to produce angiogenesis when injected directly into the myocardium in a number of different animal models [10][11][12][13] resulting in increased collateral blood flow to ischemic myocardium and improved cardiac function.…”

Section: Introductionmentioning

confidence: 99%