Pulmonary hypertension: diagnostic method to test the true curative efficacy of a drug

Background The current evaluation of drug efficacy for treating pulmonary hypertension is also based on the reduction in pulmonary vascular resistance (PVR). However, this parameter can hide systematic errors of interpretation if the role of intrapulmonary arteriovenous anastomoses (IPAVA) is not considered. Methods This study formalizes a physical-mathematical model in which the pulmonary circuit behaves like an electrical circuit with parallel resistances: arteriolar resistance (RQp) and IPAVA resistance (RQipava). The model was applied to analyse data that are normally analysed separately (decoupling of hemodynamic-metabolic data) and explain a phenomenon that has long been observed experimentally by physiologists. Results The results indicate that a decrease in IPAVA resistance (RQipava = -24.05 WU versus placebo) induces a reduction in PVR (− 0.25 WU versus placebo), which masks a decrease in effective capillary flow (Qp = -1.08 L/min vs placebo), leading to a deterioration in gas exchange (reduction in \(\:{\text{V}\text{C}\text{O}}_{2}\)). This phenomenon suggests that therapeutic efficacy based solely on PVR may be a hemodynamic illusion with potential iatrogenic risks for the patient. Conclusions A paradigm shift is needed to integrate hemodynamic parameters with metabolic coupling (Lavoisier's law). This method offers a framework for precision medicine, enabling more accurate pharmacovigilance and the development of new therapeutic targets on the basis of more patient specific, granular hemodynamic data.