Dexmedetomidine and hemodynamic responses to simulated hemorrhage in experimental heart failure.
alpha(2)-Adrenoreceptor agonists may counteract the increased basal sympathetic nervous activity in patients with congestive heart failure (CHF), but they may also compromise reflex responses to hypovolemia. We have tested responses to simulated hemorrhage (central hypovolemia) after IV dexmedetomidine in normal animals and in experimental chronic CHF. Rabbits (n = 14) were treated with IV doxorubicin (or control saline) for 8 weeks inducing biventricular dilatation and myocardial damage. Cardiac output (CO) was measured continuously with a transit-time Doppler implanted on the ascending aorta. Progressive inflation of a cuff around the inferior vena cava (simulated hemorrhage) was used to reduce cardiac index at a constant rate. Arterial baroreceptor-mediated vasoconstrictor and heart rate responses were tested with repeated cuff inflations. Although resting CO was reduced in CHF, the blood pressure and heart rate changes with dexmedetomidine were not exaggerated. The slope of the vasoconstrictor response to graded hypovolemia was attenuated by dexmedetomidine with an earlier onset of decompensation. There was no added effect of CHF on the response until the dose of dexmedetomidine was sufficient to reduce resting CO in addition to arterial blood pressure and heart rate.


CONCLUSIONS
As an adjunct to anesthesia, dexmedetomidine may be useful in reducing basal sympathetic nervous activity. This study in experimental animals suggests this may be achieved without compromising protective responses to decreased blood volume.
Blake
D W
DW
Department of Pharmacology, Anesthesia Research Unit, University of Melbourne, Victoria, Australia. d.blake@pharmacology.unimelb.edu.au
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D020927:Dexmedetomidine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006470:Hemorrhage / Q000150:complications*; D020896:Hypovolemia / Q000150:complications / Q000503:physiopathology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D020927:Dexmedetomidine