OCULAR EFFECTS OF TOPICAL ADMINISTRATION OF THE PHOSPHODIESTERASE-IIIINHIBITOR MILRINONE IN RABBITS AND CATS

Increases in intracellular cAMP levels have previously been shown to d ecrease intraocular pressure (IOP) and increase ocular blood flow (OBF ). However, the ocular effects of milrinone, which increases intracell ular cAMP levels via selective cAMP PDE III inhibition, have not been investigated. The purpose of this study was to investigate the ocular effects of topically administered milrinone at different concentration s in rabbits and cats. When compared to vehicle in conscious rabbits, topical administration of milrinone at 0.03% decreased IOP (-14.1 +/- 2.6% vs. - 7.4 +/- 3.7%, max. changes expressed as mean +/- SEM), at 0 . 1 % increased IOP (10.4 +/-8.5% vs. -1.7 +/- 4.1%), and at 0.01% and 1% did not significantly affect IOP. Neither pupil size nor central c orneal thickness were affected by milrinone. Additionally, there were no signs of inflammation and no effects on corneal clarity. In anesthe tized cats, topical administration of milrinone at 0.01-0.3% increased OBF (38.9 +/- 6. 0% for milrinone vs. -7.4 +/- 4.4% for vehicle), and at 0.03%-0.3% decreased mean arterial pressure (-19.0 +/- 5.6 vs. 3.0 +/- 4.1 mmHg) in a dose-related manner The durations of OBF enhanceme nt (1.5-2.5 h) and MAP reduction (less than 30 min to 2 h) were also d ose-dependent. In conclusion, milrinone induced biphasic IOP effects: IOP was decreased at 0.03% but increased at 0. 1%. Milrinone at 0. 01% increased OBF possibly via a local vasodilator effect, and at 0.03-0. 3% increased OBF possibly via local and systemic effects. These data s uggest that cAMP PDE III inhibitors such as milrinone may have efficac y as agents which enhance ocular blood flow following topical ocular a pplication.