Nitric Oxide based Antibacterial Modification of Cardiac Pacing Leads

Introduction: Pacing systems like any other artificial material in the body, serve as a nidus for bacterial growth, and are highly susceptible to bacterial infections (endocarditis). Coating pacemaker leads with potent antibacterial substances may be beneficial in reducing infection rates. Nitric oxide (NO) is known for its antithrombogenic and dual antibacterial properties (i)antibiofouling and (ii)bactericidal. We developed surface-modified pacemaker leads coated with either of two nitric oxide releasing molecules: diazeniumdiolated dibutylhexanediamine (DBHD/N 2 O 2 ), and S-nitroso-1-adamantanethiol (SNAT) to test the consequences of this modification in the prevention of infections and its biocompatibility in organisms. Methods: Lead refinement was developed and tested in vitro & in vivo conditions. A silicone pacing lead was coated with either 25 weight % DBHD/N 2 O 2 (group 1, n=8) or 600 mg/mL SNAT (group 2, n=6). Rate of actual nitric oxide release was assessed at 37°C and pH 7.4. After exposure to bacterial cultures (staphylococcus aureus or pseudomonas aeruginosa), effects of nitric oxide on biofilm reduction were assessed by the quantification of surface biofilm. In the in-vivo experiment, the coated leads were implanted in a leporine (rabbit) model for long-term testing of pacing parameters, pacing lead durability and the animals’ pathophysiological response to the implantation. Results: The initial nitric oxide flux was 5.75±0.25 [x10 -10 mol/min/cm2] and persisted above the antibacterial threshold >0.5 for 7 days for the DBHD/N 2 O 2 -coated lead, and 78.13±4.99 [x10 -10 mol/min/cm2] with 3 days above the threshold for the SNAT-coated lead. In-vitro bacterial testing with S. aureus demonstrated a significant reduction in biofilm in both groups compared to the control by 3 orders of magnitude of CFU: 9±3 [x10 6 ] in the control group vs. 3±0.2 [x10 3 ] in the DBHD/N 2 0 2 group vs 3±1 [x10 3 ] in the SNAT group. Similar testing with P. aeruginosa also demonstrated a 2-3 log reduction vs. control: 7±1 [x10 6 ] in the control group vs. 5±1 [x10 4 ] in the DBHD vs 4±1 [x10 3 ] in the SNAT group. In-vivo, all animals (n=14) tolerated the procedure well and demonstrated good healing. The mean sensed myocardial potential in the DBHD group was 6.0±2.3 mV and pacing threshold 2.1±0.9 V while mean lead impedance was 644±218 Ω. In the SNAT group, sensed myocardial potential was 3.9±0.6 mV and pacing threshold 2.0±0.7 V while lead impedance was 541±364 Ω. Sensed potentials in group 2 were lower compared to group 1, but measurements in both experimental groups were not different compared to an untreated lead. All parameters remained stable throughout follow up period of up to 24 months. Parameters of inflammation and methemoglobin as signs of possible toxicity were not increased; no signs of local inflammation, infection, or excessive fibrosis were observed on necropsy. Conclusion: Application of a nitric oxide releasing material to a silicone pacing lead demonstrated a potent antibacterial effect while maintaining optimal parameters. This effective elimination of biofilm formation if tested clinically, could reduce the risk of infections, especially in complex procedures and immunocompromised patients and extend durability of the pacing systems. Ministry of Health CZ-DRO (NNH, 00023884), IG240506 grant This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.