The effects of poloxamer-188 on left ventricular function in chronic heart failure after myocardial infarction.
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 groups: control, 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.
Department of Medicine, Section of Cardiology, Southern Arizona VA Health Care System, the Sarver Heart Center, The University of Arizona, Tucson, AZ, USA. elizabeth.juneman@va.gov
Elizabeth B
EB
Juneman
Laith
L
Saleh
Jordan J
JJ
Lancaster
Hoang M
HM
Thai
Bruce
B
Markham
Steven
S
Goldman
D000818:Animals; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D020442:Poloxamer / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D020442:Poloxamer