The Effects of Poloxamer-188 on Left Ventricular Function in Chronic Heart Failure After Myocardial Infarction

• Published in: Journal of cardiovascular pharmacology Vol. 60; no. 3; pp. 293 - 298
• Main Authors: Juneman, Elizabeth B, Saleh, Laith, Lancaster, Jordan J, Thai, Hoang M, Markham, Bruce, Goldman, Steven
• Format: Journal Article
• Language: English
• Published: United States Lippincott Williams & Wilkins, Inc 01-09-2012
• Subjects: Animals; Heart Failure - drug therapy; Heart Failure - physiopathology; Male; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Poloxamer - pharmacology; Poloxamer - therapeutic use; Rats; Rats, Sprague-Dawley; Treatment Outcome; Ventricular Function, Left - drug effects; Ventricular Function, Left - physiology
• ISSN: 0160-2446; 1533-4023
• DOI: 10.1097/FJC.0b013e31825f6f88

BACKGROUND:Poloxamer-188 (P-188) is a biological membrane sealant that prevents the unregulated entry of Ca into cardiomyocytes and has been shown to have the ability to act as a membrane-repair agent in isolated cardiac myocytes. The purpose of this study was to determine if treatment with P-188 would improve left ventricular (LV) function in a rat chronic heart failure (CHF) model.
METHODS:We ligated the left coronary artery of adult male Sprague–Dawley rats to induce a myocardial infarction (MI). The rats were allowed to recover for 8 weeks until stable CHF was present and treated with a range of P-188 doses [1.5 mg/kg (N = 6), 4.6 mg/kg (N = 11), 15.3 mg/kg (N = 11), and 460 mg/kg (N = 6)] delivered via 30 minutes of intravenous infusion. The rats were randomized to study groupscontrol, 2 hours, 24 hours, 48 hours, 1 week, and 2 weeks posttreatment (N = 8 in each group).
RESULTS:Two weeks after high dose (460 mg/kg) administration, P-188 improved (P < 0.05) left ventricular ejection fraction from 34% to 51%, which persisted over 38 hours and decreased (P < 0.05) LV end systolic diameter from 0.9 ± 0.07 to 0.6 ± 0.08 cm, in the rats with CHF. There was no statistical change in hemodynamics. Additionally, P-188 reduced (P < 0.05) circulating troponin levels 2 weeks after treatment.
CONCLUSIONS:Treatment with P-188 improves the LV function and partially reverses maladaptive LV remodeling in rats with moderate CHF after MI. These data introduce the idea of using a biological membrane sealant as a new approach to treating CHF after MI.