Search

In addition to central effects, which are the basis of their use in anesthesiology, alpha 2-adrenergic agonists have direct peripheral cardiovascular effects. Dexmedetomidine (DM) has been found to depress cardiac function in dogs, even after autonomic denervation. The present experiments evaluated the effects of DM on coronary flow, myocardial oxygen extraction, and cardiac function in intact, open chest dogs under enflurane anesthesia. Heart rate (HR), mean arterial pressure (MAP), left ventricular end-diastolic pressure (LVEDP), the first derivative of systolic left ventricular pressure (dP/dtmax), and flow in the left anterior descending coronary artery (CBF) were measured and continuously recorded. Cardiac output (CO), plasma catecholamines (CA), hemoglobin and oxygen saturation in arterial, mixed venous, and coronary sinus blood were measured at intervals. Cardiac index (CI), systemic vascular resistance index (SVRI), regional coronary vascular resistance (CVR), and oxygen concentration differences across the systemic [C(a-v)O2], and coronary [C(a-cs)O2] circulations were calculated. DM doses of 0.25, 0.5, 1.0, 2.0, and 4.0 micrograms/kg were given IV at 20-minute intervals. Measurements and samples were taken at peak drug effects and just prior to the next dose. The alpha 2-antagonist atipamezole, 0.5 mg/kg, was given after the last dose of DM. DM caused immediate dose-dependent increases in SVRI, CVR, LVEDP, C(a-v)O2, and C(a-cs)O2, and decreases in HR, and CI, with recovery between doses. DP/dtmax declined after the first two doses and stabilized thereafter, as plasma CA fell to minimal levels. Atipamezole completely reversed all changes.(ABSTRACT TRUNCATED AT 250 WORDS)

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.