(1180) Pulmonary Pulse Wave Analysis: A Novel Model to Identify Vascular Injury in Pulmonary Hypertension

Introduction: The elastic properties of the pulmonary vascular network play a key role in pulmonary vascular disease development. Signs of worsening stiffness in vessels can be detected by wave reflections in arterial pressure and flow waves forms. We introduce a novel model that utilizes reflected distal pressure waves to predict early signs of mechanical injury and progression of vascular disease.

Methods: Clinical and animal experimental data were used to develop the model and calculate work patterns, including stress and strain, using energy dissipation fractal dimension (X) and arterial elastance. Animal models were utilized to obtain hemodynamics. High Pressure and flow were achieved by placing fetal aortopulmonary shunt and performing right side hemodynamics postnatally. Waves were processed and evaluated for dampening and noise. Wave reflection coefficients were isolated using a novel Cepstrum spectral analysis method and waves reflected from proximal (main pulmonary) and distal (peripheral) areas were isolated. Reflection coefficients were used to calculate fractal dimension (X) and main pulmonary artery bifurcation ratio. Free energy, strain rate and flux were calculated and classified on their corresponding manifolds into 1st and 2nd order phase transition.

Results: Pulmonary wave analysis demonstrated reflected wave from main pulmonary artery and distal vasculature. Comparing control and shunt mechanical variables yielded different phase transition states at pressure < 25mmHg. Control sheep at 2-4 weeks had X>2 and 1st order phase transition state. Shunt sheep at 2-4 weeks had fractal dimension X>2 and 2nd order phase transition at critical states of elevated stress and strain rate. When evaluating 8 weeks and older sheep, the shunt sheep transitioned to X < 2 and increased stress, strain rate and 2nd order phase transition.

Conclusions: Mechanical injury with increased stress, strain and decreased free energy dissipation identifies early injury prior to development of remodeling and at subclinical pulmonary pressures. Phase transition from 1st to 2nd order in control and shunted sheep at subclinical pressures (P < 25mmHg) implies early injury and inflammation. Correlation of results with biomarkers of inflammation and remodeling is needed to validate the results.