Comparison of 3 methods to induce acute pulmonary hypertension in pigs

Large animal models for acute pulmonary hypertension (PHT) show distinct differences between species and underlying mechanisms. Two embolic procedures and continuous infusion of a stable thromboxane A(2) analogue (U46619) were explored for their ability to induce PHT and their effects on right ventricular function and pulmonary and systemic circulation in 9 pigs. Injection of small (100 to 200 microm) or large (355 to 425 microm) polystyrene beads and incremental dosage (0.2 to 0.8 microg kg(-1) min(-1)) of U46619 all induced PHT. However, infusion of U46619 resulted in stable PHT, whereas that after bead injection demonstrated a gradual continuous decline in pressure. This instability was most pronounced with small beads, due to right ventricular failure and consecutive circulatory collapse. Furthermore, cardiac output decreased during U46619 infusion but increased after embolization with no relevant differences in systemic pressure. This result was likely due to the more pronounced effect of U46619 on pulmonary resistance and impedance in combination with limited effects on pulmonary gas exchange. Coronary autoregulation and adaption of contractility to afterload increase was not impaired by U46619. All parameters returned to baseline values after infusion was discontinued. Continuous infusion of a thromboxane A2 analogue is an excellent method for induction of stable, acute PHT in large animal hemodynamic studies.