BS74 Assessment of fluid status in porcine models of heart failure and pulmonary hypertension

Background Heart failure is characterized by fluid retention the management of which is critical to clinical care. Due to altered capillary Starling forces in heart failure, the interstitial compartment and lymphatic system act as large reservoirs of fluid accumulation, increasing up to 3-4 times to that of the intravascular compartment. Interstitial fluid pressure (IFP) correlates with indicators of impaired cardiac function including reduced cardiac output and increased cardiac filling pressures. IFP may be measured from a preserved fluid pocket following the maturation of a subcutaneous perforated capsule in animals. However, the structural understanding of tissue neovascularization within a perforated capsule and the temporal relationship between cardiopulmonary haemodynamics and IFP are unknown. Methods Seven Yorkshire White swine (45-50kg) were implanted with subcutaneous perforated capsules (Home Office Project Licence PP1785781). After 3 weeks animals were anaesthetised and continuous monitoring of IFP, LVEDP, CVP and mPAP was established. Esmolol (10mg/ml, 50ml/hr) was used to blunt the sympathetic response and heart failure induced by infusion of 0.9% NaCl (10% body weight/3 hours, i.v.) until a central venous pressure (CVP) of >15mmHg was maintained. Fluid was then removed to euvolemia via ultrafiltration (3 hours) [figure 1]. To characterise the perforated capsule: 1) serial measurements of venous, interstitial, and subcutaneous glucose were made following a venous glucose bolus (0.5g/kg); 2) a silicone-based liquid perfusion-fixation agent was infused into the arterial system to cast the vasculature for MicroCT and microscopy. Results Histology and MicroCT showed neovascularisation of the perforated capsule with a central fluid pocket in communication with the systemic vasculature [figure 2A-D]. A venous bolus of glucose results in diffusion of the micro-molecule from the vasculature into the fluid pocket, however, the large molecule Microfil (silicone-based casting dye) does not diffuse, thereby confirming that the new blood vessels function as a capillary barrier between the vascular and interstitial compartment [figure 3]. IFP, as measured from the perforated fluid pocket, was closely associated with LVEDP, mPAP and CVP during the induction of heart failure and ultrafiltration [figure 4]. Conclusion Interstitial fluid pressure is closely related to invasive hemodynamic indicators of congestion and heart failure. A mature perforated capsule forms a neovascular structure with a central fluid pocket. IFP is closely related to LVEDP at rest and during a haemodynamic challenge. The assessment of interstitial fluid pressure may provide a direct measure of fluid status and an indirect measure of haemodynamics facilitating early identification of clinical worsening and optimization of fluid balance. Conflict of Interest none

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