title: Dopexamine reverses the vasopressin-associated impairment in tissue oxygen supply but decreases systemic blood pressure in ovine endotoxemia.
abstract: Since arginine vasopressin (AVP) may reduce cardiac output and, in proportion, oxygen delivery, we studied the efficacy of dopexamine (DPX) as an adjunct to AVP infusion. After 1 h of continuous AVP infusion (0.04 U/min) in healthy sheep (n = 7), DPX was additionally administered in incremental doses (1, 5, and 10 microg. kg(-1). min(-1); each dose for 30 min). After a 24-h period of recovery, endotoxin was continuously infused in the same sheep to induce and maintain a hypotensive/hyperdynamic circulation. After 16 h of endotoxemia, AVP and DPX were given as described previously. AVP infusion increased systemic vascular resistance index and decreased cardiac index in both healthy and endotoxemic conditions (P < 0.001 each). This was accompanied by an augmented pulmonary vascular resistance index in endotoxemia (159 +/- 13 dynes. cm(-5). m(-2) versus 202 +/- 16 dynes. cm(-5). m(-2)) and a decrease in oxygen delivery index (health: 842 +/- 66 mL. min(-2). m(-2) versus 475 +/- 38 mL. min(-2). m(-2); endotoxemia: 1073 +/- 49 mL. min(-2). m(-2) versus 613 +/- 44 mL. min(-2). m(-2)) and mixed venous oxygen content (health: 63% +/- 2% versus 47% +/- 2%; endotoxemia: 68% +/- 2% versus 51% +/- 3%; P < 0.001 each). Small doses of DPX (1 and 5 microg. kg(-1). min(-1)) improved not only the AVP-associated depressions in cardiac index, oxygen delivery index, and mixed venous oxygen content, but also the pulmonary vasopressive effect in both groups. While large-dose DPX (10 microg. kg(-1). min(-1)) also reduced mean pulmonary arterial pressure in endotoxemia (27 +/- 1 mm Hg versus 23 +/- 1 mm Hg; P < 0.05 versus baseline), mean arterial blood pressure decreased (105 +/- 4 mm Hg versus 80 +/- 3 mm Hg) and heart rate increased (84 +/- 4 bpm versus 136 +/- 9 bpm; P < 0.001 versus AVP alone), thereby limiting its therapeutic use.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Muenster, Muenster, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Westphal
authors.forename: Andreas Wilhelm
authors.initials: AW
authors.lastname: Sielenkämper
authors.forename: Hugo
authors.initials: H
authors.lastname: Van Aken
authors.forename: Henning Dirk
authors.initials: HD
authors.lastname: Stubbe
authors.forename: Fritz
authors.initials: F
authors.lastname: Daudel
authors.forename: Ralf
authors.initials: R
authors.lastname: Schepers
authors.forename: Simone
authors.initials: S
authors.lastname: Schulte
authors.forename: Hans-Georg
authors.initials: HG
authors.lastname: Bone
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019446:Endotoxemia / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D012756:Sheep
chemical_list: D001127:Arginine Vasopressin; C046318:dopexamine; D010100:Oxygen; D004298:Dopamine