Pulmonary vasoconstriction plays a major role in the acute phase of pulmonary embolism in pigs

Abstract

Abstract Background Pulmonary vascular resistance (PVR) increases in acute pulmonary embolism (PE) due to both mechanical obstruction and pulmonary vasoconstriction. Attenuation of adverse pulmonary vasoconstriction has shown promise as a treatment of acute PE in experimental studies. However, clinical trials have failed to replicate these beneficial effects in PE patients. Time may be a factor in this discrepancy between experimental and clinical studies. In experimental PE studies, PVR acutely increases and decreases within hours. Meanwhile in clinical trials, the time from symptom onset to study inclusion is often days, at which time PVR may already be decreased. Whether this decrease in PVR is due to reduced mechanical obstruction by endogenous fibrinolysis or attenuation of adverse pulmonary vasoconstriction is unknown. Purpose To investigate the contribution of the mechanical obstruction and pulmonary vasoconstriction to PVR in two days following PE in pigs. Methods In a controlled animal study, using an estabilished model of autologous PE in pigs (PE, n=12 ∼60 kg), changes in pulmonary hemodynamics and clot burden were evaluated. CT pulmonary angiograms were performed at baseline (BL), after acute PE and the following two days, quantifying clot burden using the Qanadli Obstruction Score. Hemodynamics were evaluated with real-time biventricular catheterization and systemic invasive pressures. To evaluate the vasoactive component, pulmonary vasodilators sildenafil (bolus 0.1 mg/kg) and oxygen (inspired fraction of oxygen 40%) were administered. Results Following PE, both mean PVR (Figure 1A) and pulmonary obstruction scores (Figure 1B) increased. PVR decreased at day one and remained unchanged at day two (Figure 1A). Meanwhile, mean obstruction score decreased slightly at day one but remained elevated throughout the study (Figure 1B). Vasodilatation induced by sildenafil and oxygen (SIL+OXY) decreased PVR at day zero but displayed no effect on the subsequent days (Figure 1A). Conclusion Pulmonary vasoconstriction and mechanical obstruction both contributed to the increase in PVR during the acute phase of PE. PVR decreased towards levels of baseline already day one and remained unchanged at day two. The contribution of pulmonary vasoconstriction decreased at day one and two, while the mechanical obstruction remained significantly increased. Accordingly, the effects of pulmonary vasodilators were only present in the acute phase of PE.Figure 1