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Background‘Healthy’ aging drives structural and functional changes in the heart including maladaptive electrical remodeling, fibrosis and inflammation, which lower the threshold for cardiovascular diseases such as heart failure (HF) and atrial fibrillation (AF). Despite mixed results in recent clinical trials, Relaxin-therapy for 2-days could reduce mortality by 37% at 180-days post-treatment, in patients with acute decompensated HF. Relaxin’s short life-span (hours) but long-lasting protective actions led us to test the hypothesis that relaxin acts at a genomic level to reverse maladaptive remodeling in aging and HF.Methods and resultsYoung (9-month) and aged (24-month), male and female F-344/Brown Norway rats were treated with relaxin (0.4 mg/kg/day) for 2-weeks delivered by subcutaneous osmotic mini-pumps or with sodium acetate (controls). The genomic effects of aging and relaxin were evaluated by extracting RNA from the left ventricles and analyzing genomic changes by RNA-sequencing, Ingenuity Pathway Analysis, MetaCore and tissue immunohistochemistry. We found that aging promotes a native inflammatory response with distinct sex-differences and relaxin suppresses transcription of multiple genes and signaling pathways associated with inflammation and HF in both genders. In addition, aging significantly increased: macrophage infiltration and atrial natriuretic peptide levels in female ventricles, and activation of the complement cascade, whereas relaxin reversed these age-related effects.ConclusionThese data support the hypothesis that relaxin alters gene transcription and suppresses inflammatory pathways and genes associated with HF and aging. Relaxin’s suppression of inflammation and fibrosis supports its potential as a therapy for cardiovascular and inflammation-related diseases, such as HF, AF and diabetes.

While the impact of injection laryngoplasty on voice outcomes in unilateral vocal fold immobility has been well characterized, there is a relative paucity of literature investigating its influence on swallow function and outcomes. We performed a retrospective chart review of patients presenting to an academic cancer center between January 2014 and January 2016 to evaluate the clinical impact of percutaneous injection laryngoplasty on reduction of aspiration risk, patient perception of swallowing, and recommended safe diet in patients with vocal fold immobility after head and neck and thoracic surgery. A consecutive sample of patients diagnosed with unilateral vocal fold immobility with patient- or clinician-identified abnormal swallow function who underwent bedside or in-office vocal fold injection was included in the study. Fiberoptic endoscopic evaluation of swallowing, Eating Assessment Tool-10 scores, Functional Oral Intake Scale scores, and patient perceptual assessment of swallow were evaluated pre- and postinjection. Twenty-one patients with new-onset unilateral vocal fold immobility who underwent injection laryngoplasty were evaluated. Median Eating Assessment Tool-10 and Functional Oral Intake Scale scores postinjection were significantly improved from preinjection. Patients who initially required restricted oral diets, or were nil per os, were able to advance their diet after injection laryngoplasty. Injection laryngoplasty is a safe and effective intervention for improvement of dysphagia in patients with unilateral vocal fold immobility. A single treatment may markedly reduce or eliminate risk of aspiration and potential sequelae.

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