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Author Notes:

Address for reprint requests and other correspondence: D. J. Lefer, Div. of Cardiothoracic Surgery, Dept. of Surgery, Emory Univ. School of Medicine, 550 Peachtree St. NE, Atlanta, GA 30308 (e-mail: dlefer@emory.edu).

B. L. Predmore and K. Kondo contributed equally to this work.

Subjects:

Research Funding:

This work was supported by National Heart, Lung, and Blood Institute Grants 5-R01-HL-092141-03 and 5-R01-HL-093579-03 (to D. J. Lefer). This work was also supported by funding from the Carlyle Fraser Heart Center of Emory University Hospital Midtown.

Keywords:

  • cardioprotection
  • nitrite
  • left ventricular function
  • nitrosothiols
  • reperfusion injury
  • endothelial nitric oxide synthase

The polysulfide diallyl trisulfide protects the ischemic myocardium by preservation of endogenous hydrogen sulfide and increasing nitric oxide bioavailability

Tools:

Journal Title:

AJP - Heart and Circulatory Physiology

Volume:

Volume 302, Number 11

Publisher:

, Pages H2410-H2418

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Diallyl trisulfide (DATS), a polysulfide constituent found in garlic oil, is capable of the release of hydrogen sulfide (H2S). H2S is a known cardioprotective agent that protects the heart via antioxidant, antiapoptotic, anti-inflammatory, and mitochondrial actions. Here, we investigated DATS as a stable donor of H2S during myocardial ischemia-reperfusion (MI/R) injury in vivo. We investigated endogenous H2S levels, infarct size, postischemic left ventricular function, mitochondrial respiration and coupling, endothelial nitric oxide (NO) synthase (eNOS) activation, and nuclear E2-related factor (Nrf2) translocation after DATS treatment. Mice were anesthetized and subjected to a surgical model of MI/R injury with and without DATS treatment (200 μg/kg). Both circulating and myocardial H2S levels were determined using chemiluminescent gas chromatography. Infarct size was measured after 45 min of ischemia and 24 h of reperfusion. Troponin I release was measured at 2, 4, and 24 h after reperfusion. Cardiac function was measured at baseline and 72 h after reperfusion by echocardiography. Cardiac mitochondria were isolated after MI/R, and mitochondrial respiration was investigated. NO metabolites, eNOS phosphorylation, and Nrf2 translocation were determined 30 min and 2 h after DATS administration. Myocardial H2S levels markedly decreased after I/R injury but were rescued by DATS treatment (P < 0.05). DATS administration significantly reduced infarct size per area at risk and per left ventricular area compared with control (P < 0.001) as well as circulating troponin I levels at 4 and 24 h (P < 0.05). Myocardial contractile function was significantly better in DATS-treated hearts compared with vehicle treatment (P < 0.05) 72 h after reperfusion. DATS reduced mitochondrial respiration in a concentration-dependent manner and significantly improved mitochondrial coupling after reperfusion (P < 0.01). DATS activated eNOS (P < 0.05) and increased NO metabolites (P < 0.05). DATS did not appear to significantly induce the Nrf2 pathway. Taken together, these data suggest that DATS is a donor of H2S that can be used as a cardioprotective agent to treat MI/R injury.

Copyright information:

© 2012 the American Physiological Society

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