Amrinone reduces pulmonary vascular resistance elevated by U46619 in isolated perfused lungs.
The effects of amrinone on pulmonary vascular resistance (PVR) were studied in an isolated, perfused rabbit lung model where all the major determinants of PVR were controlled. In this preparation, the alveolar oxygen and carbon dioxide tensions, vascular pH and vascular oxygen and carbon dioxide tensions, and zonal conditions of the lung and phasic variations of pulmonary artery pressures could be precisely measured and controlled. Measurements of PVR were made by a complete determination of the pulmonary pressure-flow curve and determination of the PVR under identical flow conditions for all studies. This approach allowed a more precise determination of the primary effects of amrinone on normal and elevated PVR than has been previously possible. We found that amrinone in final concentrations of either 4 or 8 micrograms/ml had no effect on basal PVR and no effect on lung water weight to dry ratios. When PVR was elevated by the addition of the thromboxane A2 mimetic U46619, amrinone reduced the PVR by 27% at a final concentration of 4 micrograms/ml and by 74% at a final concentration of 8 micrograms/ml. We conclude that in the doses tested, amrinone has no effects on basal PVR but is able to reduce elevated PVR in a dose-dependent manner. These results are the first to demonstrate clearly that amrinone has the ability to reduce elevated pulmonary vascular tone through a direct mechanism and not through secondary effects on other determinants of PVR such as left atrial pressure (Pla), increased cardiac output with resultant vascular recruitment, or increases in mixed venous oxygen tension. The possible implications for the clinical use of amrinone in situations of elevated PVR are discussed.
Clarke
W R
WR
Department of Anesthesiology, University of Washington, Seattle.
Morray
J P
JP
Powers
K
K
Soltow
L O
LO
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000676:Amrinone / Q000494:pharmacology*; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects*
D011450:Prostaglandin Endoperoxides, Synthetic; D002245:Carbon Dioxide; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000676:Amrinone