Effects of ketamine on in vivo cardiac sympathetic nerve endings

Using the dialysis technique, we examined the effect of ketamine on dialysa te norepinephrine (NE) levels in the myocardial interstitial space in anest hetized cats. Dialysis probes were implanted in the left ventricular myocar dium, and we measured the dialysate NE levels serving as an indicator of NE output at the cardiac sympathetic nerve endings. During local administrati on of ketamine (10 mM), we examined the time-course of the change in dialys ate NE levels and the dialysate NE response to coronary occlusion. Dialysat e NE levels significantly increased from 39 +/- 7 pg/ml at control to 133 /- 22 pg/ml 30 min after beginning the ketamine administration. Addition of either omega -conotoxin GVIA (N-type calcium channel blocker) at 10 mug/kg intravenously or desipramine (neuronal NE transport blocker) at 100 muM di d not inhibit the increment in dialysate NE evoked by ketamine. These findi ngs suggest that the increase in dialysate NE evoked by ketamine is depende nt neither on the activity of NE exocytosis nor on the neuronal NE transpor t. Left descending coronary artery occlusion evoked increments in dialysate NE. The addition of ketamine augmented the dialysate NE response to corona ry occlusion. A ketamine-induced increment in dialysate NE might occur as a consequence of NE exocytosis independent or membrane NE transport insensit ive efflux of NE.