THE ATRIAL-NATRIURETIC-PEPTIDE RECEPTOR ANTAGONIST HS-142-1 IMPROVES CARDIOVASCULAR FILLING AND MEAN ARTERIAL-PRESSURE IN A HYPERDYNAMIC OVINE MODEL OF SEPSIS

Objective: To test whether systemic vascular resistance and mean arter ial pressure increase during the administration of the atrial natriure tic peptide antagonist, HS 142-1, in ovine experimental hyperdynamic s epsis. Design: Prospective trial. Setting: Research laboratory at a la rge university medical center. Subjects: Chronically instrumented Meri no breed ewes (n = 14). Interventions: Continuous infusion of Pseudomo nas aeruginosa (2.5 x 10(6) colony-forming units/min) for the experime ntal period of 48 hrs, One group (HS 142-1) received a continuous infu sion of HS 142-1 (3 mg/kg/hr) from 40 to 48 hrs; the remaining sheep ( ''control'') were given the vehicle sodium chloride 0.9%, Measurements and Main Results: All sheep developed a hyperdynamic cardiovascular r esponse by 40 hrs that was characterized by low values of systemic vas cular resistance index (p < .05) and mean arterial pressure (p < .05), and an increased cardiac index (p < .05), HS 142-1 increased cardiac filling pressures (p < .05) without apparent effects on fluid balance, and was associated with a significantly (p < .05) higher mean arteria l pressure than was found in the control group at 44 and 48 hrs, HS 14 2-1 did not change systemic vascular resistance index, At 44 and 48 hr s, cardiac index values were found to have significantly (p < .05) inc reased in the animals receiving HS 142-1, when these data were compare d with cardiac output values at 40 hrs. Conclusion: HS 142-1 increases cardiac filling pressures and maintains mean arterial pressure in hyp erdynamic sepsis without reversal of sepsis induced vasodilation.