August 1, 1994Journal of Clinical Investigation306 citationsOpen Access
Basic fibroblast growth factor improves myocardial function in chronically ischemic porcine hearts.
Key Result
Basic fibroblast growth factor administration reduced left ventricular infarct size (1.2% vs 5.1%) and prevented pacing-induced hemodynamic deterioration in chronically ischemic porcine hearts.
Structured PICO
Does extraluminal administration of bFGF improve myocardial function, blood flow, and reduce infarct size in a porcine model of chronic myocardial ischemia?
P
Population
26 Yorkshire pigs with ameroid constrictor-induced chronic myocardial ischemia, followed for 5-8 weeks.
I
Intervention
Basic fibroblast growth factor (bFGF) administered extraluminally to the proximal left anterior descending (LAD) and circumflex arteries via calcium alginate capsules encapsulating heparin-sepharose beads (total dose 4-5 µg/animal).
C
Comparator
Ameroid constrictor placed around the proximal circumflex artery without any heparin-alginate beads (n=7) or with heparin-alginate beads not containing bFGF (n=6).
O
Outcome
Left ventricular infarct size, regional myocardial blood flow, and regional myocardial function (percent fractional shortening) at rest and during rapid pacing.surrogate
Periadventitial administration of bFGF in a porcine model of gradual coronary occlusion improves coronary flow, reduces infarct size, and prevents pacing-induced hemodynamic deterioration.
Main Result
Absolute Event Rate: 1.2% vs 5.1%
p-value: p=<0.05
Limitations
- Potential delayed closure of ameroid constrictor in bFGF-treated animals due to local vasodilatory effects
- Possible baseline differences in the degree of preexisting collateral circulation between the two groups
- Optimal dose, length, or route of administration of bFGF remains unclear
- Does not address the effectiveness of bFGF in myocardium that is already ischemic, as seen in clinical settings
- Periadventitial administration requires open-chest surgery, whereas intracoronary delivery would be clinically preferable
Abstract
The effect of basic fibroblast growth factor (bFGF) administration on regional myocardial function and blood flow in chronically ischemic hearts was studied in 26 pigs instrumented with proximal circumflex coronary artery (LCX) ameroid constrictors. In 13 animals bFGF was administered extraluminally to the proximal left anterior descending (LAD) and LCX arteries with heparin-alginate beads and 13 other animal served as controls. bFGF-treated pigs showed a fourfold reduction in left ventricular infarct size compared to untreated controls (infarct size: 1.2 +/- 0.4% vs. 5.1 +/- 1.3% of LV mass, mean +/- SEM, P 30.5 +/- 8.5%, P 14.3 +/- 7.0%, P = NS). Furthermore, LV end-diastolic pressure rise with rapid pacing was less in bFGF-treated than control pigs (pre-pacing; pacing; post-pacing, 10 +/- 1; 17 +/- 3; 11 +/- 1* mmHg vs 10 +/- 1; 24 +/- 4; 15 +/- 1 mmHg, *P < 0.05 vs. control). Coronary blood flow in the LCX territory (normalized for LAD flow) was also better during pacing in bFGF-treated pigs than in controls. Thus, periadventitial administration of bFGF in a gradual coronary occlusion model in pigs results in improvement of coronary flow and reduction in infarct size in the compromised territory as well as in prevention of pacing-induced hemodynamic deterioration.