Key Points
- Researchers used focused ultrasound to neuromodulate the inflammatory pathways in the spleen that contribute to the development of pulmonary hypertension.
- This preclinical work highlights the spleen’s role in regulating the body’s immune reaction to pulmonary hypertension.
A research team led by Stavros Zanos, MD, PhD, at the Feinstein Institutes for Medical Research and Northwell Health recently published the results from preclinical experiments using splenic focused ultrasound (sFUS) to neuromodulate the inflammatory pathways that lead to pulmonary hypertension.
“This is the first study showing the effectiveness of a noninvasive ultrasound treatment targeting the spleen as a possible therapy for pulmonary arterial hypertension,” said Kevin J. Tracey, MD, Karches Family Distinguished Chair in Medical Research, in the Feinstein Institutes press release. “Dr. Zanos’s novel research highlights the importance to continue producing knowledge about bioelectronic medicine’s potential to treat this condition and other inflammatory diseases.”
The researchers used a custom-made focused ultrasound system to test previously established neuromodulation parameters proven to activate the splenic nerve’s anti-inflammatory neuroimmune pathway (0.83 MPa, pulsing frequency of 1.1 MHz, and pulse repetition period of 0.5 ms). Two different rat models of pulmonary hypertension underwent 12-minute treatments for 14 days and were randomized to the treatment or a sham group. Outcomes were assessed with catheterization, echocardiography, autonomic function indices, histology, immunohistochemistry, spleen flow cytometry, and RNA sequencing from lung cells.
Regarding results, the treatments led to improvements in:
- Pulmonary hemodynamics, including right ventricular systolic pressure (a decrease of 25 to 30% compared with sham) and right atrial pressure; importantly, with no impact on systemic hemodynamics
- Heart rate variability and baroreflex sensitivity, markers of autonomic balance
- Brain natriuretic peptide, a pulmonary hypertension risk biomarker
- Immune cell populations in the spleen, including macrophages and cytotoxic T-cells
- Inflammatory cell infiltration in the lung, including suppression of CD3+ and CD68+ cells
- Wall thickness, apoptosis, and proliferation in small pulmonary arterioles
Importantly, the manuscript states that “Beneficial effects persist for weeks after sFUS discontinuation and are more robust with early and longer treatment.” The authors concluded that “sFUS normalizes immune cell populations in the spleen and downregulates inflammatory genes and pathways in the lung.”
The study provides additional evidence for the therapeutic potential of focused ultrasound to treat, or become an adjunct treatment for, pulmonary hypertension (see the May 2023 publication listed below).
“The current therapy for pulmonary hypertension is limited by its detrimental impacts on the non-pulmonary circulation,” says Tim Meakem, MD, a managing director at the Foundation and co-director of the research and education team. “This study’s non-pharmacologic intervention appears to be safe, wide ranging in its mechanism of action, and without the risks associated with medications.”
In an accompanying editorial, “EnFUSiasm for Healing: Ultrasound Neuromodulation in PAH,” the authors raise the importance of the spleen in regulating the body’s immune reaction to pulmonary hypertension. They then express support for the use of focused ultrasound neuromodulation in treating the involved list of symptoms in a non-pharmacological manner.
Dr. Zanos recently discussed his research on the Foundation’s Curing with Sound podcast. The Focused Ultrasound Foundation funded some of the earlier research in this area.
See Circulation Research (Open Access)
See the press release from Feinstein Institutes for Medical Research.
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