Age-associated changes leading to a decline in cardiac structure and function contribute to the increased susceptibility and incidence of cardiovascular diseases (CVD) in elderly individuals. Indeed, age is considered a risk factor for heart failure and serves as an important predictor for poor prognosis in elderly individuals. Effects stemming from chronic, low-grade inflammation, inflammaging, are considered important determinants in cardiac health; however, our understanding of the mechanisms involved remains unresolved. A steady decline in mitochondrial function is recognized as an important biological consequence found in the aging heart which contributes to the development of heart failure. Dysfunctional mitochondria contribute to increased cellular stress and an innate immune response by activating the NLRP-3 inflammasomes, which have a role in inflammaging and age-related CVD pathogenesis. Emerging evidence suggests a protective role for CYP450 epoxygenase metabolites of N-3 and N-6 polyunsaturated fatty acids (PUFA), epoxylipids, which modulate various aspects of the immune system and protect mitochondria. In this article, we provide insight into the potential roles N-3 and N-6 PUFA have modulating mitochondria, inflammaging and heart failure.

Activation of the nucleotide-binding oligomerization domain-like receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome cascade has a role in the pathogenesis of ischemia/reperfusion (IR) injury. There is growing evidence indicating cytochrome p450 (CYP450)-derived metabolites of n-3 and n-6 polyunsaturated fatty acids (PUFAs) possess both adverse and protective effects in the heart. CYP-derived epoxy metabolites are rapidly hydrolyzed by the soluble epoxide hydrolase (sEH). The current study hypothesized that the cardioprotective effects of inhibiting sEH involves limiting activation of the NLRP3 inflammasome. Isolated hearts from young wild-type (WT) and sEH null mice were perfused in the Langendorff mode with either vehicle or the specific sEH inhibitor t-AUCB. Improved post-ischemic functional recovery and better mitochondrial respiration were observed in both sEH null hearts or WT hearts perfused with t-AUCB. Inhibition of sEH markedly attenuated the activation of the NLRP3 inflammasome complex and limited the mitochondrial localization of the fission protein dynamin-related protein-1 (Drp-1) triggered by IR injury. Cardioprotective effects stemming from the inhibition of sEH included preserved activities of both cytosolic thioredoxin (Trx)-1 and mitochondrial Trx-2 antioxidant enzymes. Together, these data demonstrate that inhibiting sEH imparts cardioprotection against IR injury via maintaining post-ischemic mitochondrial function and attenuating a detrimental innate inflammatory response.

Background: Topical tranexamic acid (TXA), often combined with epinephrine, is used to reduce perioperative bleeding. This systematic review evaluates the safety and effectiveness of this combination across surgical procedures. Methods: A comprehensive search of eight databases was conducted from inception to 26 June 2025. Studies were eligible if they compared topically or locally applied TXA with epinephrine to epinephrine alone in surgical patients. Animal studies, case reports, non-English publications, and studies without comparators were excluded. Screening, data extraction, and risk of bias assessments followed PRISMA guidelines. Results: Ten studies met inclusion criteria (four randomized and six non-randomized), covering burn surgery, rhytidectomy, liposuction, septoplasty, endoscopic sinus surgery, dacryocystorhinostomy, and joint arthroplasty. TXA was applied topically or via tumescent infiltration. Most studies reported reduced intraoperative blood loss, improved surgical field visibility, lower drain output, shorter hemostasis time, and reduced transfusion rates. No increase in thromboembolic or major complications was observed. Conclusion: The combination of TXA and epinephrine appears safe and maybe effective for perioperative bleeding control. However, heterogeneity in dosing and outcomes limits generalizability. Further research is needed to standardize protocols and confirm long-term safety.