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Effects of Cimaglermin alfa Administration on LV Function in Rats with Chronic Heart Failure Induced by LAD Occlusion
Author(s) -
Ganguly Anindita,
Zolty Ronald,
Troy Erika,
Iaci Jennifer,
Hackett Craig,
Caggiano Anthony,
Parry Tom J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1197.3
Subject(s) - medicine , ejection fraction , heart failure , ligation , cardiology , myocardial infarction , cardiac function curve , ventricular function , anesthesia
Neuregulin growth factors are essential for the normal development and function of the heart. Neuregulins have been found to protect and restore left ventricular (LV) function in a variety of species with heart failure (HF) induced by myocardial infarction (MI). No report so far has shown the effect of neuregulin administration on LV function when treatment is delayed until 20‐weeks post‐MI in rats. Aim The goal of this study was to examine the effects of delayed treatment with the neuregulin, cimaglermin, on LV function (echocardiographic) and characterize the effects of withdrawal and re‐initiation of treatment in rats with chronic HF induced by LAD ligation. Methods LAD ligation was performed in (n=10–12/group) 8–10 week old male Sprague Dawley rats. At 20 weeks post‐ligation, rats were randomly assigned to vehicle or cimaglermin (0.5 and 2.6 mg/kg IV or 2.6 and 10 mg/kg SC) treatment twice weekly for 1 month. This was followed by a 1 month treatment‐free period and a re‐treatment period similar to the first. Echocardiographic parameters were assessed at least once weekly throughout the study. Results Ejection fraction (%EF) and end systolic volume (ESV) improved with intravenous and subcutaneous cimaglermin treatment. Both %EF and ESV reverted to vehicle‐treated levels during a 4 week washout of cimaglermin with both routes of administration. At an intravenous dose of 0.5 mg/kg, the changes in %EF and ESV were significantly different from vehicle control during the re‐treatment period. At 2.6 mg/kg IV, the %EF (see graph) and ESV improved significantly during both treatment periods (p<0.05). For subcutaneous dosing, %EF improved significantly vs vehicle treatment during the initial and re‐treatment periods (p<0.05) at both SC doses while ESV trended toward improvement compared to vehicle controls at the high SC dose. Conclusions Cimaglermin treatment initiated at 20 weeks post‐MI produced significant improvement in LV function in rats. Cimaglermin re‐treatment following a 4 week withdrawal period produced LV functional improvements similar to those seen with initial treatment.