ALLEVIATION OF THE PERIPHERAL HEMODYNAMIC-EFFECTS OF DEXMEDETOMIDINE BY THE CALCIUM-CHANNEL BLOCKER ISRADIPINE

Background: Alpha(2)-adrenergic agonists have peripheral vasoconstrict ive effects and central sympatholytic and sedative effects. Whereas th e latter are the basis of their use in anesthesia, the former could li mit their clinical application. Methods: To study whether a vasodilato r could alleviate the systemic and coronary vasoconstrictor effects of dexmedetomidine without influencing the central sympatholytic effects , the calcium channel blocker isradipine was infused after a high dose of dexmedetomidine in anesthetized dogs. Results: Dexmedetomidine 10 mu g.kg(-1) decreased plasma concentrations of norepinephrine and epin ephrine by more than 90%, heart rate by 39%, cardiac output by 64%, dp /dt(max) by 29% and increased mean arterial pressure by 55% and the le ft ventricular end-diastolic pressure (LVEDP) 4-fold as compared to ba seline. In addition, coronary blood flow decreased by 52% and coronary venous oxygen saturation by 51%. Isradipine could completely antagoni ze all the coronary and systemic hemodynamic changes induced by dexmed etomidine, but only partially he increase in LVEDP. Isradipine caused no changes in plasma catecholamine levels. Conclusion: Isradipine coul d alleviate the peripheral hemodynamic actions of dexmedetomidine whil e having no effect on its central sympatholytic properties.