Contribution of oxidative stress to AF electrograms
The invention relates generally to methods of detecting reactive oxygen species (ROS) in cardiac tissue and treatment modalities for ablating ROS-associated tissue in cardiac disease. The methods rely upon targeting ROS-associated cardiac tissue for ablation and/or gene therapy in a subject using analytical tools based upon a plurality of recorded atrial EGMs for a tissue to assess ROS content and underlying AF organization as a function of ROS blockade conditions.
1. A method of reducing reactive oxygen species-associated (ROS-associated) cardiac tissue in a subject, comprising:
(a) providing an isolated therapeutic DNA comprising a dominant negative TGF-β R2 cDNA expression vector that encodes and expresses dominant negative TGF-β R2 mRNA and protein in vivo or a NOX2 shRNA transgene expression vector that encodes and expresses NOX2 shRNA in vivo;
(b) administering the isolated therapeutic DNA to myocardial tissue of the subject;
(c) assessing ROS-associated cardiac tissue status of plurality of recorded atrial EGMs for a region of the myocardial tissue after administration of the therapeutic DNA; and
(d) determining a first outcome of executing step (b) and a second outcome of executing step (b) for a region based upon the one or more continued significant changes in EGM characteristics with administration of the therapeutic DNA,
wherein the first outcome triggers a first decision to forego therapy of the analysis and the second outcome triggers a second decision to perform therapy of the analysis region of the tissue.
2. The method of claim 1 , wherein step (c) comprises analyzing the plurality of recorded atrial EGMs using at least one analytical subroutine selected from the group consisting of dominant frequency analysis (DF), organizational index analysis (OI), fractional interval analysis (FI) and Shannon Entropy analysis (ShEn).
3. The method of claim 1 , wherein the first outcome consists of no continued significant changes in EGM characteristics following administration of the therapeutic DNA and the second outcome consists of at least one continued significant change in EGM characteristics following administration of the therapeutic DNA.
4. The method of claim 1 , wherein the subject is a patient in need of preventative treatment for stroke or congestive heart failure as a result of atrial fibrillation.
5. The method of claim 1 , wherein no continued significant changes in EGM characteristics is indicative of an increase in ROS-associated cardiac tissue and wherein at least one continued significant change in EGM characteristics is indicative of a reduction in ROS-associated cardiac tissue.
6. The method of claim 1 , wherein the myocardial tissue comprises PLA.
7. The method of claim 1 , wherein administering the isolated therapeutic DNA to myocardial tissue of the subject comprises injecting the isolated therapeutic DNA.