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The dithiol antioxidant, bucillamine, protects against cardiac dysfunction and remodeling in a murine model of myocardial ischemia‐reperfusion injury
Author(s) -
Ambler S. Kelly,
Hodges Yvonne K.,
Jones Gayle M.,
Long Carlin S.,
Horwitz Lawrence D.
Publication year - 2006
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.20.4.a230-a
Subject(s) - medicine , myocardial ischemia , antioxidant , ischemia , reperfusion injury , pharmacology , cardiology , cardiac dysfunction , chemistry , heart failure , biochemistry
It is well established that restoration of blood flow through occluded arteries improves outcome following myocardial infarction. Paradoxically, restoration of flow may offset the benefit of reoxygenation due to the production of reactive oxygen species (ROS) that can alter signal transduction and cause cellular damage. We thus tested the ability of the potent dithiol antioxidant, bucillamine, to protect against long‐term ischemia‐reperfusion (I/R) injury in a mouse model of myocardial infarction. Myocardial ischemia was achieved by transiently occluding the left anterior descending coronary artery for 30 minutes. Within 5 minutes of initiating reperfusion, saline or bucillamine was administered via tail vein injection. Drug treatment continued with daily subcutaneous injections for 4 weeks. Bucillamine was effective in partially preserving cardiac function following I/R injury, as determined by echocardiographic measurement of fractional shortening (saline: sham 53∀1%, I/R 35∀ 4%; bucillamine: sham 51∀3%, I/R 41∀4%; mean ∀ SE; p < 0.05, sham vs I/R, saline I/R vs bucillamine I/R). Furthermore, I/R induction of changes in hypertrophic gene expression (ANP, α‐ and β‐myosin heavy chain, SERCA), as measured by ribonuclease protection assay, was also attenuated by bucillamine. We conclude that prolonged administration of a potent dithiol antioxidant preserves ventricular function and attenuates abnormal gene expression associated with pathologic cardiac remodeling. Supported by NIH HL55291 (LDH) and HL66399 (CSL).