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Protective effect of the hydrogen sulfide donor IK‐1001 in a rat model of myocardial ischemia‐reperfusion injury: comparison with ischemic preconditioning
Author(s) -
Su Chienmin Frank,
Szabo Csaba,
Toombs Christopher
Publication year - 2008
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.22.1_supplement.1130.15
Subject(s) - cardioprotection , medicine , ischemic preconditioning , ligature , ischemia , reperfusion injury , anesthesia , cardiology
In this study, we optimized the timing regiment of IK‐1001, a novel parenteral H2S donor required for cardioprotection in a rat model of myocardial ischemia reperfusion injury. Myocardial ischemia/reperfusion was produced in anesthetized and ventilated male Sprague‐Dawley rats by tightening a ligature on the left main coronary artery for 30 min then releasing it, followed by overnight reperfusion and recovery. Animals were randomized to receive intravenous IK‐1001 or vehicle at various time point; or ischemic preconditioning (IPC: 3x, 5 min I/R) as a positive control. Infarct size was determined by planimetry using TTC. Similar to effect of preconditioning, IK‐1001 (3.85 mg/kg) injected just prior to the ischemia reduced the infarct size by 63% and no difference in AAR. Less protection was found when IK was administered delayed at later phase of ischemia (1.5 min before reperfusion) and early reperfusion (1.5 min after reperfusion). Combining the treatment with hydrogen sulfide donor with IPC failed to show additional benefit as compared to preconditioning alone. Thus, prophylactic treatment of the novel sulfide donor IK‐1001 or initiating sulfide therapy at the time just prior to reperfusion results in infarct size reduction in a setting of myocardial I/R. Moreover, the benefit does not interfere or surpass the IPC protection.