ENDOTHELIN INFUSION REDUCES HYPOXIC PULMONARY-HYPERTENSION IN PIGS IN-VIVO

Previous work has shown that the plasma levels of the potent vasoactiv e peptide endothelin (ET) are increased in pathophysiological conditio ns with increased pulmonary vascular resistance and it has been specul ated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET-infusion in the porcine pul monary circulation after hypoxia-induced hypertension. Pigs under gene ral anaesthesia were artificially ventilated through an endotracheal t ube and hypoxia was induced by decreasing the fraction inhaled O-2 fro m 0.21 to 0.10. Haemodynamic parameters were continuously recorded usi ng a Swan-Ganz catheter in combination with thermodilution for cardiac output measurements. ET-1 or ET-3 was given as an i.v. infusion throu gh the Swan-Ganz catheter in the right ventricle. Hypoxia induced a re producible increase in pulmonary vascular resistance (PVR), mean pulmo nary artery pressure (MPAP) and right ventricular stroke work (RVSW) w hile the systemic vascular resistance (SVR) slightly decreased. Cumula tive infusion of ET-1 (10, 25 and 50 ng kg(-1) min(-1)) dose-dependent ly decreased MPAP and PVR; at a higher dose (100 ng kg(-1) min(-1)), t he PVR returned to the level observed at hypoxia. ET-infusions at 50 a nd 100 ng kg(-1) min(-1) evoked an increase in SVR and a decrease in c ardiac output (GO) and stroke volume (SV). RVSW also gradually decreas ed during ET-1 infusion. Infusion of ET-3 evoked effects similar to th ose of ET-1 infusions, although the response to ET-3 was not that rapi d in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent incre ase in PVR, MPAP and RVSW which returned to baseline values during nor moxia. Infusion of ET-1 (25 ng kg(-1) min(-1)) evoked a rapidly develo ping decrease in PVR and MPAP which was quickly normalized upon cessat ion of the ET-infusion. ET-1 infusion at this concentration did not pe t se influence the haemodynamic parameters during normoxia. It is conc luded that in the pig, short-term ET-infusion reduces the pulmonary hy pertension associated with acute hypoxia.