Table 2.

Recent resolution strategies in experimental models of RHD. Review of recently tested resolution strategies in the treatment of arrhythmogenic structural and electrical remodeling resulting from severe pulmonary hypertension generated by MCT and SuHx in rats. RvD1 has been shown to significantly reduce atrial fibrous content while decreasing AF vulnerability in MCT rats. DA prevented ventricular arrhythmias via reduction of NFκB activity in MCT rats. RLX prevented atrial and ventricular fibrosis and fibrillation, while reducing the expression of notorious proinflammatory cytokines and proteins. Abbreviations: AF: Atrial Fibrillation; CHEMR23: chemerin receptor 23; COL: Collagenase; DA: dapaglifozin; ICAM1: intracellular adhesion molecule 1; IL: interleukin; i.p.: intra peritoneal; MMP: Matrix Metalloproteinase; MCT: monocrotaline; NLRP3: NACHT, LRR, and PYD domains-containing protein 3; NFκB: Nuclear Factor kappa B; NRF2: nuclear factor erythroid-derived 2; RLX: relaxin; RvD1: resolvin D1; sc.: subcutanous; SuHx: Sugen-Hypoxia; TGF-β: Transforming Growth Factor Beta; TLR4: toll-like receptor 4; VF: Ventricular Fibrillation.

Experimental Models of RHD	Resolution Strategies	Anti-Arrhythmogenic Effects	References
Monocrotaline (MCT)	Resolvin D1 (RvD1) (i.p.: 2 µg/kg/d; 3w)	• ↓ Atrial fibrosis • ↓ Expression of IL6, TGF-β, ICAM1, IL1β NLRP3-inflammasome • ↑ Expression of IL10, CHEMR23 • ↓ AF susceptibility	Hiram et al., 2021 [54]
	Dapagliflozin (DA) (per os: 60 mg/L; 4w)	• ↓ Ventricular fibrosis • Prevented channelopathy • ↓ TLR4 and NFκB activity • ↓ VF vulnerability	Qin et al., 2022 [127]
Sugen-Hypoxia (SuHx)	Relaxin (RLX) (sc.: 30–400 µg/kg/d; 6w)	• ↓ NRF2 and gluthathione transferase • ↓ Expression of TGF-β, MMP2, MMP9, COLI and COLIII • ↓ Ventricular fibrosis and VF • ↓ Atrial fibrosis and AF	Martin et al., 2021 [119] Parikh et al., 2013 [130]