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Cardioprotection by Poloxamer 188 is Mediated by Nitric Oxide Synthase
Author(s) -
Salzman Michele,
Cheng Qunli,
Matsuura Timothy,
Yannopoulos Demetris,
Riess Matthias
Publication year - 2015
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.29.1_supplement.1026.5
Subject(s) - cardioprotection , myocardial infarction , medicine , nitric oxide , nitric oxide synthase , poloxamer , cardiology , perfusion , ischemia , anesthesia , chemistry , organic chemistry , copolymer , polymer
The tri‐block copolymer Poloxamer 188 (P188) attenuates myocardial ischemia/reperfusion (I/R) injury in porcine models of acute regional myocardial infarction and cardiac arrest. We tested its cardioprotective effects in a rat isolated heart model. METHODS: After 35 minutes baseline perfusion, Langendorff‐prepared hearts from Brown Norway rats were subjected to 30 minutes global no‐flow ischemia. On reperfusion, hearts were randomized to receive vehicle, P188, the nitric oxide synthase inhibitor Nω‐Nitro‐L‐arginine methyl ester (L‐NAME), or P188+L‐NAME for 120 minutes. Left ventricular pressure (LVP), its derivatives, and coronary flow (CF) before, during and after I/R and infarct size (IS) were measured.
RESULTS: Functional improvement and IS reduction by P188 were abolished by L‐NAME. Table: Coronary & myocardial function and tissue viability after I/RVehicle L‐NAME P188 P188+L‐NAME SysLVP 65.4±1.9 62.2±2.6 59.0±1.1 62.9±5.5 DiaLVP 32.3±4.1 33.4±3.1 19.3±2.2*†‡ 29.8±2.5 DevLVP 30.7±2.1 34.5±4.3 45.4±2.2*†‡ 30.4±6.4 dPdt max 38.8±3.7 39.9±5.5 54.5±2.4*†‡ 35.5±7.8 CF 64.6±5.3 77.7±3.3*† 73.0±2.5*† 64.0±4.3 IS 39.1±4.0 32.4±2.2 18.5±1.4*†‡ 31.1±3.4[Sys: systolic; Dia: diastolic; Dev: developed; all data are % baseline at 120 minutes reperfusion (except for DiaLVP in mmHg and IS in %); statistics: ANOVA and SNK, alpha .05, *vs Vehicle, †vs P188+L‐NAME, ‡vs L‐NAME] DISCUSSION Maintaining cell membrane integrity is critical for preservation of cellular and subcellular functions and to prevent cell death. P188 offers an efficient way to attenuate I/R injury when given upon reperfusion. Direct or indirect release of nitric oxide appears to play a decisive role. Supported by Department of Veterans Affairs (CARA‐026‐10F), NIH and institutional funds.