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American Heart Association

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Final ID: Sa4132

Role of Cardiomyocyte Mechanotransduction in Triggering Atrial Arrhythmias in Pulmonary Hypertension

Abstract Body (Do not enter title and authors here): Introduction: Pulmonary arterial hypertension (PAH) is a chronic disease associated with atrial fibrillation (AF). Chronic pressure overload in right atria (RA) may disrupt cardiomyocyte mechanotransduction resulting in remodeling that triggers arrhythmias. The mechanosensitive adaptor protein, vinculin, interacts with Nav1.5 as well as indirectly stabilizing connexin-43 gap junctions.
Goal: To show that the influence of chronic overload in RA under conditions of PAH disrupts mechanotransduction signaling and increases susceptibility to arrhythmias.
Methods: We used the Sugen/Hypoxia (Su/Hx) rat model of PAH for optical mapping of action potentials in isolated right atria as well as immunohistochemistry of atrial tissue.
Results: PAH rats have enlarged RA (82.2 ± 22.3 mg PAH vs. 38.5 ± 4.7 mg control, p=0.02, t-test). In comparison to controls, isolated RA of PAH rats show slower conduction velocity (CV) (0.4 ± 0.07 mm/ms PAH vs. 0.5 ± 0.06 mm/ms control, p=0.02, t-test) together with increased local heterogeneity, an increase in APD (Fig. 1A) and APD dispersion (11.2 ± 3.7 ms PAH vs. 5.6 ± 1.3 ms control, p=0.006, t-test). Traditionally, AF is usually associated with shorter APD, so the prolonged APD we recorded in PAH RA represents a unique electrophysiological change. This electrical remodeling in PAH rats promotes conduction block in the posteromedial RA and reentry formation (Fig. 1B). Immunohistochemistry shows that vinculin is reduced at N-cadherin cell-cell contacts and redistributed to the lateral membrane in PAH RA (Fig. 2) with a 2D FFT radial sum intensity major to minor peak ratio: 1.02 ± 0.002 vs 1.008 +/- 0.001 control, p=0.02, t-test.
Conclusion: RA of PAH rats show high arrhythmia risks compared to controls. The unique electrophysiological changes could be a critical feature of AF in PAH. Vinculin redistribution may create a substrate for RA arrhythmias and may play an important role in regulating the electrical remodeling of RA in PAH.
  • Bronk, Peter  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Tran, Cao  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Choi, Bum-rak  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Zhang, Peng  ( Providence VA, Brown University , Providence , Rhode Island , United States )
  • Wang, Eric  ( Providence VA , Providence , Rhode Island , United States )
  • Lu, Yichun  ( Lifespan , Providence , Rhode Island , United States )
  • Banerjee, Debolina  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Stanley, Madigan  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Sellke, Frank  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Radice, Glenn  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Choudhary, Gaurav  ( Providence VA, Brown University , Providence , Rhode Island , United States )
  • Author Disclosures:
    Peter Bronk: DO NOT have relevant financial relationships | Cao Tran: No Answer | Bum-rak Choi: DO NOT have relevant financial relationships | Peng Zhang: DO NOT have relevant financial relationships | Eric Wang: DO NOT have relevant financial relationships | Yichun Lu: No Answer | Debolina Banerjee: DO NOT have relevant financial relationships | Madigan Stanley: DO NOT have relevant financial relationships | frank sellke: DO have relevant financial relationships ; Ownership Interest:xm therapeutics:Active (exists now) | Glenn Radice: DO NOT have relevant financial relationships | Gaurav Choudhary: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Come Together Now: Left Heart or Right Heart Dysfunction in Pulmonary Hypertension

Saturday, 11/16/2024 , 10:30AM - 11:30AM

Abstract Poster Session

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