Use of remote ischemic conditioning to improve outcome after myocardial infarction

Abstract

The invention provides methods for reducing the incidence and/or severity and/or delaying the onset of heart dysfunction/failure and improving overall survival through the use of remote ischemic per-conditioning and post-conditioning.

1 - 28 . (canceled) 
     
     
         29 . A method for reducing the incidence, delaying the onset, and/or reducing the severity of heart dysfunction and/or failure following a myocardial infarction comprising:
 performing a first remote ischemic conditioning (RIC) regimen on a subject during the myocardial infarction; and   performing second, repeated RIC regimens on the subject beginning after an ischemic phase and a reperfusion phase of the myocardial infarction and continuing for at least three days.   
     
     
         30 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced within 1 week after the myocardial infarction occurs. 
     
     
         31 . The method of  claim 29 , wherein the second, repeated RIC regimens are performed every two days. 
     
     
         32 . The method of  claim 29 , wherein the second, repeated RIC regimens are performed daily. 
     
     
         33 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced within a month after the myocardial infarction occurs. 
     
     
         34 . The method of  claim 29 , wherein the second, repeated RIC regimens are performed more than once per day on one or more days. 
     
     
         35 . The method of  claim 29 , wherein the subject has not undergone balloon angioplasty or a stent placement. 
     
     
         36 . The method of  claim 29 , wherein the first RIC regimen and each second, repeated RIC regimen comprise at least four cycles, each cycle comprising blood flow occlusion and reperfusion. 
     
     
         37 . The method of  claim 29 , wherein the first RIC regimen and each second, repeated RIC regimen comprise more than one cycle, and each cycle comprises about 5 minutes of occlusion and 5 minutes of reperfusion. 
     
     
         38 . The method of  claim 29 , wherein the first RIC regimen and each second, repeated RIC regimen are performed at the same site. 
     
     
         39 . The method of  claim 38 , wherein the first RIC regimen and each second, repeated RIC regimen are performed on an upper limb of the subject. 
     
     
         40 . The method of  claim 29 , further comprising administering to the subject an angiotensin-converting enzyme (ACE) inhibitor. 
     
     
         41 . The method of  claim 29 , further comprising administering to the subject an angiotensin II receptor blocker. 
     
     
         42 . The method of  claim 29 , further comprising administering to the subject an anti-platelet therapy. 
     
     
         43 . The method of  claim 29 , wherein 2, 3, 4, 5 or more of the second, repeated RIC regimens are performed on a subject in a single day. 
     
     
         44 . The method of  claim 29 , wherein the second, repeated RIC regimens are performed for at least 28 days after the myocardial infarction. 
     
     
         45 . The method of  claim 44 , wherein the second, repeated RIC regimens are performed for a period of one month, two months, three months, four months, five months, six months, seven months, eight months, nine months, ten months, or twelve months after the myocardial infarction occurs. 
     
     
         46 . The method of  claim 45 , wherein the second, repeated RIC regimens are performed for a remaining lifespan of the subject. 
     
     
         47 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced at least 12 hours after the myocardial infarction occurs. 
     
     
         48 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced at least 6 hours after the myocardial infarction occurs. 
     
     
         49 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced at least 24 hours after the myocardial infarction. 
     
     
         50 . The method of  claim 29 , wherein the second, repeated RIC regimens are commenced at least 36 hours after the myocardial infarction occurs. 
     
     
         51 . The method of  claim 29 , wherein adverse remodeling of a left ventricle of a heart of the subject is restricted. 
     
     
         52 . The method of  claim 29 , wherein the first RIC regimen is performed during the ischemic phase of the myocardial infarction. 
     
     
         53 . The method of  claim 29 , wherein the first RIC regimen is performed during the reperfusion phase of the myocardial infarction. 
     
     
         54 . The method of  claim 29 , wherein the first RIC regimen is performed during both the ischemic phase and the reperfusion phase of the myocardial infarction. 
     
     
         55 . A method for reducing the incidence, delaying the onset, and/or reducing the severity of heart dysfunction and/or failure following a myocardial infarction comprising:
 performing a first remote ischemic conditioning (RIC) regimen on a subject before the myocardial infarction; and   performing second, repeated RIC regimens on the subject beginning after an ischemic phase and a reperfusion phase of the myocardial infarction and continuing for at least three days.   
     
     
         56 . The method of  claim 55 , wherein adverse remodeling of a left ventricle of a heart of the subject is restricted. 
     
     
         57 . A method for reducing the incidence, delaying the onset, and/or reducing the severity of heart dysfunction and/or failure following a myocardial infarction comprising:
 performing a first remote ischemic conditioning (RIC) regimen on a subject before the myocardial infarction;   performing a second RIC regimen on the subject during the myocardial infarction; and   performing third, repeated RIC regimens on the subject beginning after an ischemic phase and a reperfusion phase of the myocardial infarction and continuing for at least three days.   
     
     
         58 . The method of  claim 57 , wherein adverse remodeling of a left ventricle of a heart of the subject is restricted. 
     
     
         59 . The method of  claim 57 , wherein the second RIC regimen is performed during the ischemic phase of the myocardial infarction. 
     
     
         60 . The method of  claim 57 , wherein the second RIC regimen is performed during the reperfusion phase of the myocardial infarction. 
     
     
         61 . The method of  claim 57 , wherein the second RIC regimen is performed during both the ischemic phase and the reperfusion phase of the myocardial infarction.