Method of producing biologically active human acidic fibroblast growth factor and its use in promoting angiogenesis
View Patent ↗The present invention relates to the treatment of coronary heart disease by revascularization therapy, and more particularly to the intramyocardial injection of a pharmaceutical composition comprising a recombinant fibroblast growth factor-1 protein or a fragment of a recombinant fibroblast growth factor-1 protein, optionally, with a physiologic glue for inducing local neoangiogenesis in ischemic myocardium. Methods of producing the recombinant fibroblast growth factor 1 protein and fragments are also disclosed.
1. A method for increasing cardiac efficiency of a heart having an ischemic myocardial region in a human subject, comprising the steps of:
(a) preparing a pharmaceutical composition comprising a recombinant fibroblast growth factor-1 (FGF-1);
(b) injecting an amount of said pharmaceutical composition into the ischemic region of the myocardium, said amount being sufficient to induce local neoangiogenesis; and
(c) evaluating at least one clinical index of cardiac function to confirm that cardiac efficiency has increased.
2. The method of claim 1 , wherein said FGF-1 is injected at a final concentration in a range of about 0.1 μg/kg body weight per site to about 10 μg/kg body weight per site.
3. The method of claim 1 wherein said FGF-1 is injected at a final concentration in a range of about 10 to 100 μg/kg body weight per site.
4. The method of claim 1 , wherein the pharmaceutical composition further comprises a physiologic glue.
5. The method of claim 4 , wherein said physiologic glue is fibrin glue.
6. The method of claim 1 , wherein said FGF-1 and said physiologic glue are mixed immediately prior to application.
7. The method of claim 1 , wherein said pharmaceutical composition further comprises an anticoagulant.
8. The method of claim 7 , wherein said anticoagulant is heparin.
9. The method of claim 8 , wherein the heparin is applied at a final concentration in a range of about 1 U per ml to about 1000 U per ml.
10. The method of claim 1 , wherein said injecting step further comprises:
making a thoracotomy incision;
identifying at least one site of coronary artery stenosis;
administering a β-blocker to reduce the heart rate to a range of about 20–60 beats per minute; and
injecting the pharmaceutical composition intramyocardially at or near the at least one site of coronary artery stenosis.
11. The method of claim 10 , wherein said thoracotomy incision further comprises an anterior left-sided incision; dissecting a region of costal cartilage over a 5 th rib; and
opening a left pleural space and a pericardium.
12. The method of claim 10 , wherein the step of identifying the at least one site of coronary artery stenosis further comprises retracting the heart forward using traction sutures.
13. The method of claim 1 , wherein the neoangiogenesis is long term and occurs in the ischemic region at 6 weeks after the injection.
14. The method of claim 1 , wherein the neoangiogenesis is long term and occurs in the ischemic region at 3 months after the injection.
15. The method of claim 1 , wherein the method further comprises performing a coronary artery bypass graft.
16. The method of claim 1 , further comprising the step of injecting a composition comprising a physiologic glue subsequent to injection with the pharmaceutical composition.
17. The method of claim 1 , wherein the ischemic region comprises at least one site in a heart wall.