Kidney Week

Abstract: SA-PO020

Pulsed Ultrasound of the Splenic Nerve Increases the Splenic Resistive Index in Humans

Session Information

• Bioengineering: Modeling, Diagnosis, Therapy
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bioengineering

• 400 Bioengineering

Authors

• Husain-Syed, Faeq, University of Virginia Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, Virginia, United States

Faeq Husain-Syed,

• Nash, William, University of Virginia Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, Virginia, United States

William Nash,

• Shumilin, Igor, University of Virginia Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, Virginia, United States

Igor Shumilin,

• Ma, Jennie Z., University of Virginia Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, Virginia, United States

Jennie Z. Ma,

• Hossack, John, University of Virginia Department of Biomedical Engineering, Charlottesville, Virginia, United States

John Hossack,

• Okusa, Mark D., University of Virginia Division of Nephrology, Center for Immunity, Inflammation and Regenerative Medicine, Charlottesville, Virginia, United States

Mark D. Okusa,

Background

Splenic pulsed ultrasound (pUS) attenuates ischemia-reperfusion injury-induced systemic inflammation and AKI in mice by activating the cholinergic anti-inflammatory reflex pathway (CAP). We aimed to translate the preclinical discoveries to human inflammation and identify clinical parameters for evaluating the efficacy of pUS. Given the dense splenic innervation by sympathetic neurons (SNs) and norepinephrine (NE) release by sympathetic nerve terminals following CAP activation, we hypothesized that NE release post-pUS increases vascular resistance and, hence, the resistive index (RI).

Methods

We analyzed data from an ongoing human pilot study that tests whether pUS within FDA-approved limits of diagnostic medical sonography attenuates inflammation and alters immune cell composition (clinicaltrials.gov; NCT05685108). Healthy adults were exposed to pUS targeting the splenic nerve with varying ultrasound intensities as defined by burst mechanical index (MI). Spectral Doppler ultrasonography was performed before, immediately after, and 24 h after pUS to determine any functional effects.

Results

23 pUS procedures were performed in 12 subjects (median age, 28 [IQR, 26 to 36] years; median BMI 24 [22 to 27] kg/m²; 50% male). We observed a significant increase in splenic RI (+0.05 [0.01 to 0.08]; P<0.001) and decrease in splenic volume (-8.4 [-23.1 to -1.1] cm³; P=0.008) immediately after pUS, but not in renal RI nor renal volume. The splenic RI increase was accompanied by an increase in the ratio of systolic-to-diastolic flow velocity, and seemed to depend on the magnitude of applied MI (Figure). 24 h post-pUS, the observed splenic changes were no longer detectable (data not shown).

Conclusion

Our preliminary results in humans demonstrate that pUS transiently increases the splenic RI. This novel physiological effect of pUS provides proof of concept that pUS activates SNs. The increase in vascular resistance may serve as a functional clinical measure of pUS and may contribute to the anti-inflammatory effect of CAP activation.

Funding

• Other NIH Support