Modeling of Acute Pulmonary Arterial Hypertension in Pigs Using a Stable Thromboxane A2 Analogue (U46619): Dose Adjustment and Assessment of Hemodynamic Reactions

Bull Exp Biol Med. 2021 Apr;170(6):729-733. doi: 10.1007/s10517-021-05142-2. Epub 2021 Apr 24.

Abstract

U46619, a synthetic analogue of thromboxane A2 was used for modeling acute stable and reversible pulmonary arterial hypertension. Administration of U46619 in high doses led to vascular collapse and inhibition of cardiac function. The doses of U46619 were empirically selected that allow attaining the target level of pulmonary hypertension without systemic hemodynamic disturbances. The possibility of attaining the target level of pulmonary hypertension and reversibility of changes after termination of U46619 infusion make this model attractive for evaluation of the efficiency of different therapeutic methods of treatment of pulmonary hypertension in large animals.

Keywords: modeling; pulmonary hypertension; synthetic analogue of thromboxane A2.

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / therapeutic use
  • Animals
  • Hemodynamics / drug effects
  • Hypertension, Pulmonary / drug therapy
  • Hypertension, Pulmonary / metabolism
  • Male
  • Pulmonary Arterial Hypertension / drug therapy*
  • Pulmonary Arterial Hypertension / metabolism
  • Swine
  • Thromboxane A2 / therapeutic use*
  • Vasoconstrictor Agents / therapeutic use*

Substances

  • Vasoconstrictor Agents
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid