Discussion
atrial cardiomyopathy, POAF, myocardial ischemia
DISEASE, EVENT, MYOCARDIAL ISCHEMIA, PATHOGENESIS, COMPLICATIONS
Conventional therapies for POAF reflect approaches to attain and maintain normal rhythm while preventing rate-related complications and systemic embolization (The pathogenesis of POAF revolves about the interaction between preoperative, perioperative, and postoperative factors (These results contrast with other preclinical approaches to POAF in several ways. First, our study design fulfills many of the SYRCLE criteria used to exclude bias (Despite these promising features and results, our study has several potential limitations that need to be acknowledged. Although rodents provide a cost-effective means of testing new therapies, their repolarizing ion channel profile and basal heart rates differ from those of humans. Rodent hearts are also inherently much smaller and do not generally exhibit spontaneous AF, requiring AF induction to obtain indices of the AF substrate. Our findings rationalize future work using large animal models that better reflect human electrophysiology and provide the opportunity for realistic clinical scaling. We also recognize that the extent to which EVs may act upon the preoperative components of the vulnerable substrate for AF is speculative and not the focus of this study, as none of the treated animals had a preexisting atrial cardiomyopathy. However, this approach has merit, as similar studies looking at delayed administration of EVs after myocardial ischemia (In summary, our study indicates that a single dose of EVs delivered at the time of open-chest surgery directly into the affected area (i.e., the atria) before the disease starts has the potential to target multiple pathways resulting in AF. Our published work has shown that scaling using serum-free, xenogen-free techniques is feasible and will provide a cost-effective product for clinical use. This approach merits future attention as assessment in patients would be relatively straightforward, the clinical problem addressed is quite significant, and clinical event rates are high.