Acute isoproterenol leads to age-dependent arrhythmogenesis in guinea pigs.

Sudden cardiac death from ventricular arrhythmias is more common in adult patients with with heart failure compared with pediatric patients with heart failure. We identified age-specific differences in arrhythmogenesis using a guinea pig model of acute ß-adrenergic stimulation. Young and adult guinea pigs were exposed to the ß-adrenergic agonist isoproterenol (ISO; 0.7 mg/kg) for 30 min in the absence or presence of flecainide (20 mg/kg), an antiarrhythmic that blocks Na+ and ryanodine channels. Implanted cardiac monitors (Reveal LINQ, Medtronic) were used to monitor heart rhythm. Alterations in phosphorylation and oxidation of ryanodine receptor 2 (RyR2) were measured in left ventricular tissue. There were age-specific differences in arrhythmogenesis and sudden death associated with acute ß-adrenergic stimulation in guinea pigs. Young and adult guinea pigs developed arrhythmias in response to ISO; however, adult animals developed significantly more premature ventricular contractions and experienced higher arrhythmia-related mortality than young guinea pigs treated with ISO. Although there were no significant differences in the phosphorylation of left ventricular RyR2 between young and adult guinea pigs, adult guinea pigs exposed to acute ISO had significantly more oxidation of RyR2. Flecainide treatment significantly improved survival and decreased the number of premature ventricular contractions in young and adult animals in association with lower RyR2 oxidation. Adult guinea pigs had a greater propensity to develop arrhythmias and suffer sudden death than young guinea pigs when acutely exposed to ISO. This was associated with higher oxidation of RyR2. The incidence of sudden death can be rescued with flecainide treatment, which decreases RyR2 oxidation. NEW & NOTEWORTHY Clinically, adult patients with heart failure are more likely to develop arrhythmias and sudden death than pediatric patients with heart failure. In the present study, older guinea pigs also showed a greater propensity to arrhythmias and sudden death than young guinea pigs when acutely exposed to isoproterenol. Although there are well-described age-related cardiac structural changes that predispose patients to arrhythmogenesis, the present data suggest contributions from dynamic changes in cellular signaling also play an important role in arrhythmogenesis.

Cataract Surgery Outcomes in Patients with Non-ocular Autoimmune Disease.

INTRODUCTION: While phacoemulsification cataract extraction is generally highly effective and safe, patients with a history of uveitis are at higher risk for postoperative complications and often require a modified perioperative medication regimen. No data exists on risks of postoperative complications and persistent anterior uveitis (PAU) in patients with non-ocular autoimmune disease. METHODS: Medical records were reviewed of patients who underwent phacoemulsification cataract surgery with intraocular lens implantation between January 1, 2014 and December 31, 2019 at the University of Colorado Hospital (UCH) as part of a retrospective cohort study. Exclusion criteria included patient history of ocular inflammation and cataract surgery combined with another intraocular surgery. Patients were only included as having autoimmune disease if the diagnosis was confirmed by a relevant specialist at UCH. Patients with autoimmune disease were then stratified into systemic versus organ-specific autoimmune disease, and patients with systemic autoimmune disease were further stratified into immunosuppressed and not immunosuppressed at the time of cataract surgery. Patients with PAU were identified according to the Standardization of Uveitis Nomenclature Working Group. Data including sex, race/ethnicity, intraoperative cumulative dissipated energy (CDE), and postoperative best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were obtained. RESULTS: A total of 422 eyes from 248 patients had confirmed autoimmune disease, compared to a control group of 10,201 eyes. The autoimmune and systemic autoimmune disease groups were not more likely to have postoperative complications or PAU compared to the control group. Immunosuppression status among the systemic autoimmune disease group was also not associated with postoperative complications or PAU. CONCLUSION: Patients with non-ocular autoimmune disease do not appear to be at higher risk for postoperative complications, including worse BCVA or increased rates of IOP elevation and PAU, following phacoemulsification cataract surgery. These patients do not appear to require modification of the typical perioperative medication regimen.

COL4A1 mutations in two infants with congenital cataracts and porencephaly: an ophthalmologic perspective.

COL4A1 mutations present with a spectrum of clinical phenotypes often involving the cerebrovascular and ophthalmic systems. We report 2 cases of COL4A1 mutations that presented with congenital cataracts and porencephaly. Both patients had posterior cortical cataracts and radiographically defined bilateral posterior lenticonus. Considering the long-term clinical implications of these mutations, posterior cortical cataracts, bilateral posterior lenticonus, and porencephaly should raise clinical suspicion for COL4A1 mutations.