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American Heart Association

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Final ID: Su4179

Role of Inflammatory Cytokines in Triggering Ventricular Arrhythmias in Pulmonary Hypertension

Abstract Body (Do not enter title and authors here): Introduction: Pulmonary hypertension (PH) is a deadly disease, and the corresponding survival rates are estimated at 50% over 5 years. Most patients with severe PH die of right heart failure or sudden cardiac death from arrhythmias. There are strong indications supporting inflammation as a major proarrhythmic factor in PH.
Goal: To investigate whether and how inflammatory cytokines promote cardiac arrhythmias in PH rat model.
Methods: We used rat models of PH: 1) decompensated PH using Su5416 injection (SU) and 3 weeks of hypoxia (Hx) (Su/Hx, n=7), 2) compensated PH using Hx alone (n=3), 3) sham control (CTR, n=8). Interleukin 1b (IL-1b) and IL-18 were perfused (5 ng/ml for 90 min) and action potentials (AP) were mapped using optical mapping with voltage sensitive dye.
Results: APDs in the right ventricle (RV) were significantly increased in Su/Hx (86±9 ms, p=0.014) vs. Hx (75±10 ms) and CTR (74±8 ms). APD dispersion is also increased in Su/Hx (23±3 ms, p=0.011) vs. Hx (8±3 ms) and CTR (9±4 ms), leading to conduction block and reentry formation around RVOT in Su/Hx during S1S2 programmed stimulation (Fig-A). Longitudinal conduction velocity (CV) is significantly slower in Su/Hx (0.58±0.08 m/s, p=0.01) vs. Hx (0.78±0.12 m/s) and CTR (0.84±0.10 m/s). Perfusion of IL-1b/IL-18 significantly prolongs APDs in the Su/Hx model (Fig-B, APD=109±19 ms, p=0.003) but not in Hx (78±13 ms) and CTR (83±7 ms), associated with frequent PVCs in Su/Hx model (Fig-C.D, n=5/7 hearts in Su/Hx vs. 0/3 in Hx only and 2/8 hearts in CTR), indicating that inflammatory cytokines increase arrhythmia risks in decompensated PH.
Conclusion: More severe form of PH (Su/Hx) showed the highest arrhythmia risks compared to the compensated PH model (Hx) and control under IL-1b/IL-18 perfusion, supporting the idea that inflammation in PH may play key roles promoting electrical remodeling and arrhythmias.
  • Bronk, Peter  ( 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 )
  • Radice, Glenn  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Tran, Cao  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Choudhary, Gaurav  ( Providence VA, Brown University , Providence , Rhode Island , United States )
  • Choi, Bum-rak  ( RIH and Brown Medical School , Providence , Rhode Island , United States )
  • Author Disclosures:
    Peter Bronk: DO NOT have relevant financial relationships | Peng Zhang: DO NOT have relevant financial relationships | Eric Wang: DO NOT have relevant financial relationships | Glenn Radice: DO NOT have relevant financial relationships | Cao Tran: No Answer | Gaurav Choudhary: DO NOT have relevant financial relationships | Bum-rak Choi: DO NOT have relevant financial relationships
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

When Cells and Molecules Go Bad: Molecular Mechanisms of Pulmonary Vascular Disease

Sunday, 11/17/2024 , 03:15PM - 04:15PM

Abstract Poster Session

More abstracts from these authors:
Role of Cardiomyocyte Mechanotransduction in Triggering Atrial Arrhythmias in Pulmonary Hypertension

Bronk Peter, Tran Cao, Choi Bum-rak, Zhang Peng, Wang Eric, Lu Yichun, Banerjee Debolina, Stanley Madigan, Sellke Frank, Radice Glenn, Choudhary Gaurav

Functional Heterogeneity of NaV1.5 in Mouse Heart

Choi Bum-rak, London Barry, Dierdorff Jason, Clark Colin, Bronk Peter, Solola Nussbaum Sade, Yoon Jin-young, Choi Hannah, Mehdi Haider, Ahern Christopher

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