Ranolazine (Ran) is a novel anti-ischemic agent with electrophysiologic properties mainly attributed to the inhibition of late Na(+) current and atrial-selective early Na(+) current. However, there are only limited data regarding its efficacy and mechanism of action against atrial flutter (Afl) and atrial fibrillation (AF) in intact animals. Therefore, we aimed to investigate the electrophysiologic mechanism of Ran in a rabbit model of inducible atrial tachyarrhythmias elicited by acetylcholine (ACh). Arrhythmias were produced in 19 rabbits by rapid atrial burst pacing during control, after intravenous ACh and after Ran + ACh administration. Recording of right atrial monophasic action potentials (MAPs) and programmed stimulation were utilized to determine the duration of atrial repolarization at various cycle lengths and voltage levels of action potential, including 75% of total MAP duration (MAPD75), effective refractory period (ERP), and postrepolarization refractoriness (PRR = ERP - MAPD75) prior to and after Ran. Control stimulation yielded no arrhythmias or maximal nonsustained runs of Afl/AF. Upon ACh, 17 of 19 rabbits exhibited sustained Afl and AF as well as mixed forms of Afl/AF, while 2 animals revealed none or short runs of nonsustained arrhythmias and were excluded from the study. High-frequency burst pacing during the first 30 minutes after Ran + ACh failed to induce any arrhythmia in 13 of 17 rabbits (76%), while 2 animals displayed sustained Afl/AF and 2 other animals nonsustained Afl/AF. At basic stimulation cycle length of 250 milliseconds, Ran prolonged baseline atrial ERP (80 ± 8 vs 120 ± 9 milliseconds, P < .001) much more than MAPD75 (65 ± 7 vs 85 ± 7 milliseconds, P < .001), leading to atrial PRR which was more pronounced after Ran compared with control measurements (35 ± 11 vs 15 ± 10 milliseconds, P < .001). This in vivo study demonstrates that Ran exerts antiarrhythmic activity by suppressing inducibility of ACh-mediated Afl/AF in intact rabbits. Its action may predominantly be related to a significant increase in atrial PRR, resulting in depressed electrical excitability and impediment of arrhythmia initiation.
We would like to report an interesting case of acute sclerokeratitis following cataract surgery treated with topical use of Cyclosporine-A. A 61-year old woman with a past history of scleritis in her right eye had an uneventful phaco surgery in her right eye for cataract removal via a corneoscleral incision. Eight months after the initial surgery the patient had a sudden decrease in her visual acquity in the right eye with marked inflammatory signs in the sclera and cornea adjacent to the entry-site of the phaco surgery. Initially the patient was treated with systemic corticosteroids but due to serious side effects topical cyclosporine-A was added instead. Five months later the patient has a significant improvement in terms of visual acquity with marked reduction in the inflammatory signs both in sclera and corneal tissue. We think that topical Cyclosporine-A with its potent immunomodulating effects seems to be of benefit in those cases where systemic corticosteroids are contraindicated or have serious side-effects.
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