HEMODYNAMIC-EFFECTS OF DEXMEDETOMIDINE, AN ALPHA-2-ADRENERGIC AGONIST, IN AUTONOMICALLY DENERVATED DOGS

被引:47
作者
FLACKE, JW [1 ]
FLACKE, WE [1 ]
BLOOR, BC [1 ]
MCINTEE, DF [1 ]
机构
[1] UNIV CALIF LOS ANGELES,SCH MED,DEPT PHARMACOL,LOS ANGELES,CA 90024
关键词
Atipamezole; Autonomically denervated dogs; Cardiovascular effects; Dexmedetomidine; α[!sub]2[!/sub]-Adrenergic agonist; α[!sub]2[!/sub]-Adrenergic antagonist;
D O I
10.1097/00005344-199010000-00013
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The hemodynamic effects of the α2-adrenergic agonist, dexmedetomidine (DM), were studied in eight anesthetized, autonomically denervated dogs. Autonomic block decreased mean arterial pressure (MAP) and cardiac index (CI) by 20% to 95 ± 8 mm Hg and 4.1 ± 0.1 L/min/m2, respectively (mean ± SEM), and reduced nor-epinephrine (NE) and epinephrine plasma levels to almost undetectable levels. DM, administered intravenously (i.v.) either by bolus injection or by slow (20 min) infusion in doses between 1 and 30 (μg/kg, had no effect on heart rate (HR), increased MAP significantly by 98%, decreased CI by 59%, and increased calculated systemic vascular resistance index (SVRI) significantly by 376%, maximally. The effect of the lowest dose was mediated mainly by arteriolar vasoconstriction, and that of higher doses was mediated by vasoconstriction and decreased CI. Left ventricular end-diastolic pressure (LVEDP) increased significantly from 6 ± 2 to > 30 mm Hg, maximally. The effects were cumulative, and the first dose caused near maximal pressor effect; the resistance increase was as great with slow infusion as with bolus injection. Prazosin (1 mg/kg) did not affect the changes, but 0.3 mg/kg atipamezole, a selective α2-antagonist, completely antagonized them. These observations demonstrate potent constriction of both arteriolar resistance and venous capacitance vasculature in dogs. The combination of decreased CI and increased filling pressure implies marked decrease in cardiac function which was, however, fully reversible by atipamezole. © 1990 Raven Press, Ltd., New York.
引用
收藏
页码:616 / 623
页数:8
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