Inhibition of src for treatment of reperfusion injury related to revascularization
The present invention provides methods for treating, preventing, or reducing reperfusion injury or post-pump syndrome by administering an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
1 . A method for treating, preventing, or reducing reperfusion injury or post-pump syndrome by administering an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
2 . The method of claim 1 , wherein the inhibitor comprises an inhibitor of a Src family kinase.
3 . The method of claim 1 , wherein the inhibitor comprises a pyrazolopyrimidin.
4 . The method of claim 1 , wherein the inhibitor comprises PP1 or PP2.
5 . The method of claim 1 , wherein the inhibitor has the chemical formula C 16 H 19 N 5 .
6 . The method of claim 1 , wherein the inhibitor comprises a quinolinecarbonitrile.
7 . The method of claim 1 , wherein the inhibitor comprises a 3-quinolinecarbonitrile.
8 . The method of claim 1 , wherein the inhibitor comprises a 4-anilino-3-quinolinecarbonitrile.
9 . The method of claim 1 , wherein the inhibitor comprises SKI-606.
10 . The method of claim 2 , wherein the Src family kinase comprises Src, Fyn, Yes, Lyn, Lck, or Hck.
11 . The method of claim 2 , wherein the Src family kinase comprises Src.
12 . The method of claim 1 , wherein the inhibitor is administered intravenously.
13 . The method of claim 1 , wherein the inhibitor is administered by intraperitoneal injection.
14 . The method of claim 1 , wherein the inhibitor is administered using an intracoronary method.
15 . The method of claim 1 , wherein the inhibitor is administered percutaneously.
16 . The method of claim 1 , wherein the reperfusion injury is the result of myocardial infarction.
17 . The method of claim 1 , wherein the reperfusion injury is the result of angina.
18 . The method of claim 1 , wherein the reperfusion injury or post-pump syndrome is the result of a coronary revascularization procedure.
19 . The method of claim 18 , wherein the coronary revascularization procedure comprises a percutaneous coronary revascularization procedure.
20 . The method of claim 19 , wherein the percutaneous coronary revascularization procedure comprises angioplasty, stent placement, or atherectomy.
21 . The method of claim 18 , wherein the coronary revascularization procedure comprises angioplasty, comprising an angioplasty balloon, wherein the balloon comprises a coating comprising an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
22 . The method of claim 21 , wherein the inhibitor comprises an inhibitor of a Src family kinase.
23 . The method of claim 18 , wherein the coronary revascularization procedure comprises angioplasty, comprising an angioplasty balloon, wherein the angioplasty balloon is capable of eluting an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
24 . The method of claim 23 , wherein the inhibitor comprises an inhibitor of a Src family kinase.
25 . The method of claim 18 , wherein the coronary revascularization procedure comprises stent placement, wherein the stent comprises a coating comprising an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
26 . The method of claim 25 , wherein the inhibitor comprises an inhibitor of a Src family kinase.
27 . The method of claim 18 , wherein the coronary revascularization procedure comprises stent placement, wherein the stent is capable of eluting an inhibitor of vascular endothelial growth factor-mediated vascular permeability.
28 . The method of claim 27 , wherein the inhibitor comprises an inhibitor of a Src family kinase.
29 . The method of claim 18 , wherein the coronary revascularization procedure comprises a surgical coronary revascularization procedure.
30 . The method of claim 29 , wherein the surgical coronary revascularization procedure comprises bypass surgery.
31 . The method of claim 1 , wherein the reperfusion injury is the result of stroke or a treatment for stroke.
32 . The method of claim 1 , wherein the reperfusion injury is the result of compartment syndrome or a treatment for compartment syndrome.
33 . A method for treating, preventing, or reducing reperfusion injury following ischemia, wherein the ischemia is caused by blockage or leakage of a blood vessel, by administering an inhibitor of vascular endothelial growth factor-mediated vascular permeability, wherein
a. the inhibitor comprises an inhibitor of a Src family kinase; and
b. the ischemia is the result of:
i. myocardial infarction;
ii. stroke;
iii. compartment syndrome;
iv. post-pump syndrome; or
v. angina.
34 . The method of claim 33 , wherein the Src family kinase comprises Src, Fyn, Yes, Lyn, Lck, or Hck.
35 . The method of claim 33 , wherein the inhibitor comprises a pyrazolopyrimidin or a 3quinolinecarbonitrile.
36 . The method of claim 33 , wherein the inhibitor comprises PP1, PP2, or SK1-606.
37 . The method of claim 33 , wherein the inhibitor is administered by intravenous, by intraperitoneal injection, by direct injection into an artery, by infusion, by an intracoronary method, or by percutaneous administration.
38 . A method for treating, preventing, or reducing injury following bypass surgery by administering an inhibitor of vascular endothelial growth factor-mediated vascular permeability, wherein the inhibitor comprises an inhibitor of a Src family kinase.
39 . The method of claim 38 , wherein the inhibitor is administered as part of the cardioplegia solution.
40 . A method for treating, preventing, or reducing reperfusion injury following compartment syndrome by administering an inhibitor of vascular endothelial growth factor-mediated vascular permeability, wherein the inhibitor comprises an inhibitor of a Src family kinase.
41 . The method of claim 40 , wherein the inhibitor is administered by infusion into a local artery during a surgical procedure for the treatment or relief of the compartment syndrome.