The effects of poloxamer-188 on left ventricular function in chronic heart failure after myocardial infarction

Elizabeth B Juneman, Laith Saleh, Jordan J. Lancaster, Hoang M. Thai, Bruce Markham, Steven Goldman

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)293-298
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume60
Issue number3
DOIs
StatePublished - Sep 2012

Fingerprint

Poloxamer
Left Ventricular Function
Heart Failure
Myocardial Infarction
Cardiac Myocytes
Membranes
Ventricular Remodeling
Troponin
Intravenous Infusions
Stroke Volume
Sprague Dawley Rats
Coronary Vessels
Therapeutics
Hemodynamics
Control Groups

Keywords

  • Ca
  • chronic heart failure
  • left ventricular ejection fraction
  • Poloxamer-188

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

The effects of poloxamer-188 on left ventricular function in chronic heart failure after myocardial infarction. / Juneman, Elizabeth B; Saleh, Laith; Lancaster, Jordan J.; Thai, Hoang M.; Markham, Bruce; Goldman, Steven.

In: Journal of Cardiovascular Pharmacology, Vol. 60, No. 3, 09.2012, p. 293-298.

Research output: Contribution to journalArticle

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abstract = "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.",
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