Abstract Body (Do not enter title and authors here): Background: Impaired blood volume shifts between different parts of the circulatory system contribute to elevated intracardiac filling pressures in patients with heart failure (HF), particularly HF with preserved ejection fraction (HFpEF) during exercise. A substantial part of the intravascular blood volume resides is in the splanchnic vasculature, which is regulated by a greater splanchnic nerve (GSN) arising from the sympathetic trunk. The GSN activation during exercise constricts splanchnic veins and shifts blood from the abdomen to the central circulation, rapidly increasing cardiac filling pressures. Recent studies have demonstrated that therapeutic interruption of the GSN holds promise to decrease congestion in patients with HFpEF. This led to the hypothesis that stimulation of the GSN could induce hemodynamic changes observed in HFpEF during exercise, allowing creation of an acute preclinical model for studying therapies for this condition.
Methods: Three anesthetized swine underwent thoracotomy to access left sympathetic trunk (Figure A, yellow arrows). Renal arteries were balloon-occluded to amplify volume overload, achieved by IV infusion of colloid fluid. Electric stimulation (20V, 2ms, 20Hz) was applied to the sympathetic trunk for 3 minutes bursts, at the end of which hemodynamic data were collected during temporarily pausing mechanical ventilation.
Results: Sympathetic trunk stimulations lead to an increase of mean aortic pressure (AoP) from 76.8±5.6 mmHg to 104.4±12.5 mmHg, pulmonary artery pressure (PAP) from 37.3±4.2 mmHg to 45.4±3.5 mmHg, central venous pressure (CVP) from 15.7±2.7 mmHg to 18.8±2.2 mmHg and pulmonary capillary wedge pressure (PCWP) from 18.7±1.7 mmHg to 24.0±2.9 mmHg (Figure B, black arrow=start of stimulation).
Conclusions: Sympathetic trunk stimulation in volume loaded healthy swine caused increase in cardiac filling pressures that mimic hemodynamic features of HFpEF during exercise. This acute model has potential for testing novel therapeutic interventions for HFpEF targeting modulation of autonomous nervous system.