Time change of nicardipine effect on choroidal circulation in rabbit eyes

To investigate the time course of effects of intravenous administration of a calcium antagonist, nicardipine, on the choroidal circulation of rabbit eyes using a laser speckle tissue circulation analyzer.

The rabbit fundus was illuminated by a diode laser spot and its image speckle was detected by an image sensor. The difference between the average of the speckle intensity (Imean) and the speckle intensity for successive scannings was calculated, and the ratio of Imean to this difference was defined as normalized blur (NB); a quantitative index of tissue blood velocity. The average NB over the field measured (0.620.62 mm in the choroid) was calculated to give Nb(av). Under general anesthesia, 0.4 ml/kg of 0.01% nicardipine hydrochloride dissolved in physiological saline was injected intravenously in a group of albino rabbits (control group) for measurement in the choroid (nicardipine groups). To serve as control, 0.4 ml/kg of physiological saline was injected in other groups of albino rabbits (control groups). Nb(av) was recorded at 1-min intervals for the first 5 min and at 5-min intervals for the next 85 min. During the experiment mean femoral arterial blood pressure (FABPm), pulse rate (PR), arterial blood pH, Pco2 and Po2 body temperature (BT) and intraocular pressure (IOP) were also monitored. Before and 45 min after nicardipine administration, the choroidal blood flow measurement using the microsphere technique and the Nb(av) measurement were carried out in the same eye in another group of rabbits.

Only the rabbits which did not show any significant change in the PR, pH, Pco2, Po2 and BT during the experiment were accepted. FABPm in the nicardipine group dropped to the minimum at 1 min postadministration and this level remained significantly lower than that in the control group up to 15 min post-injection, while te 10P did not show any significant change. The Nb(av) in the nicardipine group showed a significant increase after the FABPm return to the baseline, which was maintained throughout the experiment. The averaged increase between 30 and 90 minutes after administration was 27 +/- 1% (mean +/- S.E.M., n = 10). Relative increase in choroidal blood flow determined by the microsphere technique showed a good correlation (r = 0.90, P < 0.001, n = 12) with those determined by Nb(av) after nicardipine administration.

The present result indicates that the time course of drug effects on the choroidal circulation can be noninvasively and sensitively followed by Nb(av) measurements. Further, it was shown that nicardipine may have considerable potential for the treatment of ocular diseases associated with insufficient choroidal blood flow and that nicardipine's effects here observed deserve to be further studied in humans.