Table 3.
Effects of H2S and its donors in myocardial I/R injury.
| Experimental models | Effects | Proposed mechanisms | References |
|---|---|---|---|
| Myocardial I/R in vivo (rat) | NaHS (0.2 mg/kg, prior to R) protects against the effects of haemorrhage-induced I/R | Upregulation of the protein kinase B/endothelial nitric oxide synthase pathway | [148] |
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| Regional myocardial I/R in vivo (rat) | NaHS (3 mg/kg, 15 min prior to I) shows cardioprotective effects | Combination of antiapoptotic and anti-inflammatory effects | [149] |
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| Isolated perfused heart ex vivo (rat) | NaHS (100 μM, plus histidine buffer solution, prior to R) enhances cardiac performance | Prevention of apoptosis and preservation of the phosphorylative system | [150] |
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| Isolated perfused heart ex vivo (rat) | NaHS (0.1–100 μM, at the onset of R) protects rat heart against I/R injury | Mitochondrial KATP channel opening | [151] |
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| Primary cultured neonatal cardiomyocytes (rat) | NaHS (25–200 μM, 30 min prior to H) protects cardiomyocytes from oxidative stress | Inhibition of mitochondrial complex IV and enhancement of SOD activity | [152] |
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| Isolated perfused heart ex vivo (rat) | NaHS (10 μM, at the onset of R) protects isolated rat hearts from I/R injury | Activation of the Janus kinase 2/signal transducer and activator of transcription 3 signaling pathway | [153] |
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| Isolated perfused heart ex vivo (rat) | NaHS (40 μM, throughout the experiment) provides myocardial protection | Possibly activation of the expression of heat shock protein 72 | [154] |
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| Isolated perfused heart ex vivo (rat) | L-cysteine (0.1–10 mM, 10 min before I until 10 min after R) induces limitation of infarct size | Dependent on H2S synthesis | [155] |
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| Myocardial I/R in vivo (rat) | NaHS (14 μM/kg, 7 days before myocardial I/R) significantly reduces the myocardial infarct size | Antiapoptotic, antioxidative, and anti-inflammatory activities | [156] |
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| Isolated perfused heart ex vivo (rat) | NaHS (100 μM, prior to I) significantly decreases the duration and severity of I/R-induced arrhythmias | Mitochondrial KATP channel opening | [157] |
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| Isolated perfused heart ex vivo (rat) | NaHS (100 μM, prior to I) significantly decreases myocardial infarct size and improves heart contractile function | Activation of KATP/PKC/ERK1/2 and PI3K/Akt pathways | [158] |
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| Isolated cardiac myocytes (rat) | NaHS (100 μM, prior to I) increases cell viability, percentage of rod-shaped cells, and myocyte contractility | KATP/PKC dependent induction of COX-2 expression and nitric oxide-induced COX-2 activation | [159] |
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| Myocardial I/R in vivo (mice) | H2S (100 ppm, prior to I) has protective properties in I/R injury | Reduction of myocardial ROS production and the inhibition of inflammation, necrosis, and fibrogenesis | [36] |
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| Regional myocardial I/R in vivo (pig) | Na2S (100 μg/kg bolus + 1 mg/kg/hr infusion, 10 min prior to R) improves myocardial function and reduces infarct size | Anti-inflammatory properties | [160] |
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| Regional myocardial I/R in vivo (pig) | Na2S (100 μg/kg bolus + 1 mg/kg/hr infusion, throughout the experiment) reduces myocardial infarct size | Antiapoptotic activities | [161] |
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| Regional myocardial I/R in vivo (rat) | NaHS (0.1–10 μM, 10 min prior to I until 10 min into R) results in a concentration-dependent limitation of infarct size | Mitochondrial KATP channel opening | [162] |
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| |||
| Myocardial I/R in vivo (rat) | NaHS (0.2 mg/kg, prior to R) protects against the effects of haemorrhage-induced I/R | Protection against oxidative stress | [163] |
|
| |||
| Primary cultured neonatal cardiomyocytes (rat) | NaHS (1–100 μM, 30 min prior to H) shows concentration-dependent inhibitory effects on cardiomyocyte apoptosis induced by H/R | Induction of phosphorylation of GSK-3 and inhibition of mitochondrial permeability transition pore opening | [164] |
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| |||
| Myocardial I/R in vivo (mice) | Na2S (0.1 mg/kg, 7 days prior to I) attenuates myocardial I/R injury | Activation of nuclear factor erythroid-2-related factor-2 signaling in an Erk-dependent manner | [165] |
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| Myocardial I/R in vivo (rat) | NaHS (14 μM/kg, 7 days prior to I) inhibits apoptosis of cardiomyocytes induced by myocardial I/R | Enhancement of the phosphorylation of apoptosis repressor with caspase recruitment domain | [166] |
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| Myocardial I/R in vivo (mice) | Na2S (10–500 μg/kg, prior to R) limits infarct size and preserves left ventricular function | Inhibition of myocardial inflammation and preservation of both mitochondrial structure and function | [167] |
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| |||
| Myocardial I/R in vivo (mice) | Na2S (100 μg/kg, 1 h prior to I) reduces myocardial infarct size | miR-21-dependent attenuation of ischemic and inflammatory injury | [168] |
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| Myocardial I/R in vivo (mice) | Na2S (100 μg/kg, 24 h prior to I) reduces myocardial infarct size | Combination of antioxidant and antiapoptotic signaling | [169] |
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| Isolated perfused heart ex vivo (rabbit) | Allitridum (60 μM, prior to I) reduces myocardial infarct size | Activation of PKC | [170] |
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| Myocardial I/R in vivo (mice) | DATS (200 μg/kg, prior to R) significantly reduces infarct size and increases myocardial contractile function | Preservation of endogenous hydrogen sulfide and increase of nitric oxide bioavailability | [32] |
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| Myocardial I/R in vivo (mice) | Na2S (100 μg/kg, prior to R) protects against the structural and functional deterioration of the left ventricle | Protection against oxidative stress and mitochondrial dysfunction | [15] |
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| Isolated perfused heart ex vivo (rat) | NaHS (50 μM, prior or post to I) protects against cardiac I/R injury | Phosphorylation of mammalian target of rapamycin C2 | [171] |
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| Myocardial I/R in vivo (rat) | NaHS (3 mg/kg, 15 min prior to I) significantly reduces myocardial infarct size | Mitochondrial KATP channel opening | [172] |
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| |||
| Primary cultured neonatal cardiomyocytes (rat) | NaHS (30 μM, 30 min prior to H) attenuates cardiomyocyte apoptosis and enhances cell viability | Protection of cardiomyocytes against I/R-induced apoptosis by stimulating Bcl-2 | [173] |
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| |||
| Isolated perfused heart ex vivo (mice) | Na2S (10 μM, 40 seconds after the start of R) markedly improves the recovery of myocardial function | Nitric oxide synthase 3-dependent signaling pathway | [174] |
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| |||
| Myocardial I/R in vivo (rat) | NaHS (14 μM/kg/d, 6 d prior to I) markedly reduces heart infarct size and has great improvement in blood pressure | Upregulation of survivin | [175] |
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| Myocardial I/R in vivo (pig) | NaHS (0.2 mg/kg, prior to R) markedly reduces myocardial infarct size and improves regional left ventricular function | Higher expression of phospho-GSK-3β and lower expression of apoptosis-inducing factor | [176] |
H/R: hypoxia/reoxygenation; SOD: superoxide dismutase; PKC: protein kinase C; ERK1/2: extracellular signal regulated kinase 1/2; PI3K (PtdIns3K): phosphatidylinositol 3-kinase; Akt (PKB): protein kinase B; COX-2: cyclooxygenase-2; ROS: reactive oxygen species; GSK-3: glycogen synthase kinase-3.