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