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 arterial pressure increase during the administration of the atrial natriuretic peptide antagonist, HS 142-1, in ovine experimental hyperdynamic sepsis.


METHODS
Prospective trial.


METHODS
Research laboratory at a large university medical center.


METHODS
Chronically instrumented Merino breed ewes (n = 14).


METHODS
Continuous infusion of Pseudomonas aeruginosa (2.5 x 10(6) colony-forming units/min) for the experimental period of 48 hrs. One group (HS 142-1) received a continuous infusion 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%.


RESULTS
All sheep developed a hyperdynamic cardiovascular response by 40 hrs that was characterized by low values of systemic vascular 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 arterial pressure than was found in the control group at 44 and 48 hrs. HS 142-1 did not change systemic vascular resistance index. At 44 and 48 hrs, cardiac index values were found to have significantly (p < .05) increased in the animals receiving HS 142-1, when these data were compared with cardiac output values at 40 hrs.


CONCLUSIONS
HS 142-1 increases cardiac filling pressures and maintains mean arterial pressure in hyperdynamic sepsis without reversal of sepsis-induced vasodilation.
Hinder
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Department of Anesthesiology, University of Texas Medical Branch, Galveston 77555-0833, USA.
Booke
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D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology / Q000627:therapeutic use*; D017461:Receptors, Atrial Natriuretic Factor / Q000037:antagonists & inhibitors*; D018805:Sepsis / Q000188:drug therapy*; D012756:Sheep
C072551:HS 142-1; D011134:Polysaccharides; D017461:Receptors, Atrial Natriuretic Factor