Methods and device for synergistic mitigation of reperfusion injury after an ischemic event

• US 8,708,996 B2
• Filed: 04/29/2011
• Issued: 04/29/2014
• Est. Priority Date: 04/30/2010
• Status: Expired due to Fees

• Current Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Original Assignee: Abbott Cardiovascular Systems Incorporated (Abbott Laboratories)
• Inventors: Consigny, Paul, Ehrenreich, Kevin J., Magana, Jesus, Hossainy, Syed
• Primary Examiner(s): Lucchesi, Nicholas
• Assistant Examiner(s): Snyder, Melissa A
• Application Number:
  US13/098,055
• Publication Number:
  US 20110319866A1
• Time in Patent Office: 1,096 Days
• Field of Search: 604 9901- 9902, 604/96.01, 604/97.01, 604/98.01, 604508-509
• US Class Current: 604/509
• CPC Class Codes: A61M 2025/105 having a balloon suitable for drug delivery, e.g. by using holes for delivery, drug coating or membranes
• CPC Class Codes: A61M 25/10181 Means for forcing inflation fluid into the balloon
• CPC Class Codes: A61M 25/10184 Means for controlling or monitoring inflation or deflation
• CPC Class Codes: A61M 25/10186 One-way valves
• CPC Class Codes: A61M 25/104 used for angioplasty

Abstract

A method for synergistic mitigation of reperfusion injury after an ischemia event in a subject.

Claims

1. A method for mitigating reperfusion injury to a tissue in a subject suffering from an ischemic event in a blood vessel, the method comprising:

locally administering a calpain inhibitor to an ischemic blood vessel during a cycle of inflation and deflation of a balloon within the ischemic blood vessel during a postconditioning procedure,

wherein the calpain inhibitor is locally administered to an area of the blood vessel distal to a lesion.

2. The method of claim 1, wherein the beneficial agent is sequentially locally administered to the blood vessel during the postconditioning procedure, the postconditioning procedure including sequentially reducing perfusion to the tissue by inflating a balloon within the blood vessel for a first period of time, and allowing perfusion of the tissue by deflating the balloon within the blood vessel for a second period of time.

3. The method of claim 1, wherein the calpain inhibitor exhibits increased uptake into the tissue of the blood vessel as compared to uptake at healthy tissue.

4. The method of claim 3, wherein the increased uptake is at least four-fold as compared to uptake at healthy tissue.

5. The method of claim 1, wherein blood plasma of the subject has a concentration of calpain inhibitor at least 60 minutes after the postconditioning has ceased.

6. The method of claim 5, wherein the blood plasma has a concentration of calpain inhibitor at least 120 minutes after postconditioning has ceased.

7. The method of claim 1, wherein the tissue is myocardial, cerebral, peripheral, skeletal, or spinal.

8. A method for mitigating reperfusion injury to a tissue of a mammal, the method comprising:

sequentially reducing perfusion to the tissue by inflating a balloon within an ischemic blood vessel for a first period of time, and allowing perfusion of the tissue by deflating the balloon within the ischemic blood vessel for a second period of time, and

locally administering a beneficial agent selected from the group consisting of endothelin receptor blockers, pH stabilizing agents, and calpain inhibitors during postconditioning to a subject, wherein the beneficial agent enhances mitigation of reperfusion injury to an organ or tissue distal to an ischemia,

wherein the beneficial agent is in a vehicle having a biomaterial.

9. The method of claim 8, wherein the tissue is cerebral, myocardial, skeletal, or peripheral tissue.

10. The method of claim 9, wherein the method mitigates cerebral injury after a stroke.

11. The method of claim 9, wherein the method mitigates myocardial injury after a heart attack.

12. The method of claim 8, wherein the biomaterial increases residence time of the beneficial agent in the blood vessel.

13. The method of claim 8, wherein the endothelin receptor blocker is atrasentan.

14. The method of claim 8, wherein the pH stabilizing agent is selected from oxygen, nitric oxide, a mixture of sodium carbonate and citric acid, mixture of carbon dioxide and nitrogen dioxide.

15. A method for mitigating tissue infarction after an ischemic event, the method comprising:

introducing a balloon catheter into an ischemic blood vessel, the balloon catheter having a compliant balloon;

engaging an actuator in one motion to inflate the balloon within the ischemic blood vessel to occlude the blood flow therethrough for a first period of time;

disengaging the actuator in one motion to deflate the balloon within the blood vessel to permit at least partial reperfusion of blood flow through the blood vessel for a second period of time;

alternating the engaging and disengaging steps to alternate the inflation and deflation rounds for at least two cycles to achieve postconditioning of the ischemic blood vessel; and

sequentially administering a beneficial agent locally to the blood vessel during either inflation or deflation of the balloon, wherein the infarcted tissue exhibits a four-fold increase in uptake of the beneficial agent as compared to uptake at healthy tissue.

16. The method of claim 15, wherein the uptake of beneficial agent is increased at least forty-fold as compared to uptake at healthy tissue.

17. The method of claim 15, wherein the uptake of beneficial agent is increased at least one-hundred-fold as compared to uptake at healthy tissue.