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Sodium Nitrite Fails to Limit Myocardial Infarct Size: Results from the CAESAR Cardioprotection Consortium (LB645)
Author(s) -
Lefer David,
Jones Steven,
Steenbergen Charles,
Kukreja Rakesh,
Guo Yiru,
Tang XianLiang,
Li Qianhong,
Ockaili Ramzi,
Salloum Fadi,
Kong Maiying,
Polhemus David,
Bhushan Shashi,
Goodchild Traci,
Chang Carlos,
Book Michael,
Du Junjie,
Bolli Roberto
Publication year - 2014
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.28.1_supplement.lb645
Subject(s) - cardioprotection , medicine , sodium nitrite , myocardial infarction , nitrite , cardiology , pharmacology , chemistry , organic chemistry , nitrate
The CAESAR Consortium was established in 2010 to test promising cardioprotective agents in a manner analogous to clinical trials. This consortium features highly standardized murine, leporine, and porcine models of myocardial ischemia and reperfusion (MI/R). These models are conducted at two sites per species, in a randomized and blinded manner, and in combination with core laboratories to assess myocardial infarct size, measure cardiac troponin I levels, and perform unbiased statistical analyses. After validating the Consortium with an ischemic preconditioning study, we evaluated several putative potent cardioprotective agents (e.g. sodium nitrite). We performed preliminary studies to determine appropriate dosing and pharmacokinetics of sodium nitrite in mice and rabbits. MI/R was performed in mice (n=29‐36/group), rabbits (n=20‐22/group), and pigs (n=8/group); sodium nitrite was administered intravenously 5 min before reperfusion. We observed no differences in hemodynamics or myocardial area‐at‐risk (AAR) in any species. Sodium nitrite failed to attenuate myocardial infarct size (INF) per AAR or reduce peak blood levels of cardiac troponin I in any species.Thus, sodium nitrite does not afford acute protection during MI/R when investigated under rigorous experimental conditions that mimic clinical trials.Grant Funding Source : National Institutes of Health (NIH)‐Heart Lung and Blood Institute (NHLBI) CAESAR Consortium‐1U24 HL 094373