Effect of dexmedetomidine, an alpha 2-adrenergic agonist, in the isolated heart.
Dexmedetomidine (DM) was studied in the isolated dog heart in the form of a Starling heart-lung preparation, (HLP). Hearts were subjected to increased loading by (a) increasing cardiac output, and (b) increasing systemic resistance. Results are depicted by cardiac function curves, prepared by plotting left atrial pressure against either systemic cardiac output or mean arterial pressure. DM, given in divided doses up to 44 micrograms, had no effect on heart rate or cardiac function, nor did injection of 0.5 mg of atipamezole, a selective alpha 2-antagonist. Additional injections of very large doses of DM, up to 4,444 micrograms, caused an increase in heart rate and a leftward shift of the function curves, ie, positive chronotropic and inotropic effects. Plasma catecholamine levels increased markedly between the 444 micrograms and the 4,444 micrograms cumulative doses of DM. Administration of 1 mg of prazosin had no effect, but 1 mg of propranolol returned the rate to baseline and markedly shifted function curves to the right and depressed their slopes. Thus, whereas low doses (corresponding to between 1 and 30 micrograms/kg in intact animals) of DM, given acutely IV, have been shown to depress cardiac function in intact and denervated dogs, this effect is not due to a direct effect on the myocardium. High doses, far beyond doses maximally effective in intact animals and man, release catecholamines from cardiac stores. Plasma DM levels after low doses in the HLP were between 1 to 10 times those seen in intact animals and human volunteers after the usual doses given clinically for their central effects. Because DM caused no myocardial depressant effect in the isolated, blood-perfused canine HLP, decreases in cardiac function seen after this drug is given to intact and autonomically denervated dogs must be due to factor(s) other than a direct action on the myocardium.
Flacke
W E
WE
Department of Anesthesiology, University of California, Los Angeles.
Flacke
J W
JW
Blow
K D
KD
McIntee
D F
DF
Bloor
B C
BC
D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D016279:Atrial Function, Left / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008168:Lung; D008297:Male; D020926:Medetomidine; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014690:Venous Pressure / Q000187:drug effects
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; C050701:atipamezole; D011433:Propranolol; D020926:Medetomidine; D009638:Norepinephrine; D011224:Prazosin; D004837:Epinephrine