Splanchnic circulatory failure drives vasovagal syncope: bioimpedance profiling of regional fluid shifts and dose-response characterisation of greater splanchnic nerve stimulation
M Zuhair, N Kaza, Z Liu, P Eardley, A Ali, M Sorbini, M Dani, P Kanagaratnam, R Sutton, R Khiani, D Francis, Z Whinnett, M Shun-Shin, P B Lim, D KeeneAbstract
Background
Vasovagal syncope (VVS) is the most common cause of transient loss of consciousness (1), yet the regional fluid dynamics precipitating events remain poorly characterised. Splanchnic pooling has been implicated (2,3) but never mapped continuously alongside other compartments. Greater splanchnic nerve (GSN) stimulation raises blood pressure in canine models (4) and during human splanchnic activation (5), but the dose-response relationship is undefined. We used multi-segmental bioelectrical impedance analysis to map fluid shifts preceding syncope and performed graded GSN stimulation to characterise its dose-response effect on blood pressure.
Methods
Ninety-three adults referred for unexplained syncope underwent 70° head-up tilt testing with simultaneous three-channel BIA of thoracic, splanchnic, and thigh compartments, with beat-to-beat arterial pressure and ECG monitoring. Impedance changes were expressed as percentage change from supine baseline. In a separate substudy, two adults without syncope underwent graded percutaneous transcatheter GSN stimulation (15, 20, and 25 mA at 20 Hz) via the azygos vein during elective electrophysiology procedures with continuous invasive blood pressure monitoring.
Results
Fifty-six (60%) developed syncope. Systolic blood pressure diverged between groups three minutes before syncope (p=0.02). In the final four minutes, non-fainters showed a significant rise in splanchnic impedance (+1.4±0.3%, p=0.001) with stable thoracic impedance, indicating splanchnic-to-central autotransfusion. Fainters showed no splanchnic impedance change (−0.5±0.4%, p=0.09) but a thoracic impedance rise (+2.9±0.3%, p=0.02), indicating splanchnic pooling with central hypovolaemia. Thigh impedance decreased similarly in both groups. GSN stimulation produced a dose-dependent rise in systolic blood pressure (baseline 130.5 mmHg; 135.4 at 15 mA [p=0.22]; 138.5 at 20 mA [p=0.02]; 136.8 at 25 mA [p=0.01]), with no heart rate change. IVC control stimulation produced no effect.
Conclusions
VVS is distinguished not by excessive lower-limb pooling but by failure of splanchnic autotransfusion, resulting in central volume depletion. Graded GSN stimulation elicits a dose-dependent, heart-rate-independent pressor response, establishing splanchnic neuromodulation as a mechanism-targeted therapeutic strategy.