Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration

2005 ◽  
Vol 83 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Zhengyuan Xia ◽  
Kuo-Hsing Kuo ◽  
John H McNeill ◽  
David M Ansley
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Control Treatment ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Early Reperfusion ◽  
Endothelin 1

The purpose of this study was to investigate the effects of bosentan, a mixed endothelin receptor A and B subtype antagonist, on myocardial ischemia-reperfusion injury and to explore the influence of the timing of bosentan administration on its cardioprotective effects. Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were randomized to 1 of 3 experimental groups (n = 7 each): untreated control; treatment with bosentan 1 µmol/L 10 min prior to, during 40 min global ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1 µmol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not the BOS treatment regimen, significantly reduced the release of cardiac-specific creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control) without affecting myocardial contractility. Left ventricular developed pressure in the BOS group was significantly (P < 0.01) lower than that in the control group throughout reperfusion. It is concluded that pharmacologically delayed antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial injury. Endothelin-1 antagonist application during early reperfusion may exacerbate postischemic myocardial dysfunction.Key words: bosentan, ischemia, heart, rat, endothelin-1 antagonist.

TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1

2003 ◽  
Vol 284 (5) ◽  
pp. H1612-H1617 ◽  
Author(s):  
Hongjiang Chen ◽  
Dayuan Li ◽  
Tom Saldeen ◽  
Jawahar L. Mehta
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Left Ventricular ◽  
Blue Staining ◽  
Control Group ◽  
Dependent Manner ◽  
Arterial Blood ◽  
Group I

Ischemia-reperfusion (I/R) is thought to upregulate the expression and activity of matrix metalloproteinases (MMPs), which regulate myocardial and vascular remodeling. Previous studies have shown that transforming growth factor-β1 (TGF-β1) can attenuate myocardial injury induced by I/R. TGF-β1 is also reported to suppress the release of MMPs. To study the modulation of MMP-1 by TGF-β1 in I/R myocardium, Sprague-Dawley rats were given saline and subjected to 1 h of myocardial ischemia [total left coronary artery (LCA) ligation] followed by 1 h of reperfusion ( n = 9). Parallel groups of rats were pretreated with recombinant TGF-β1(rTGF-β1, 1 mg/rat, n = 9) before reperfusion or exposure to sham I/R (control group). I/R caused myocardial necrosis and dysfunction, indicated by decreased first derivative of left ventricular pressure, mean arterial blood pressure, and heart rate (all P < 0.01 vs. sham-operated control group). Simultaneously, I/R upregulated MMP-1 ( P < 0.01). Treatment of rats with rTGF-β1 reduced the extent of myocardial necrosis and dysfunction despite I/R (all P < 0.01). rTGF-β1 treatment also inhibited the upregulation of MMP-1 in the I/R myocardium ( P < 0.05). To determine the direct effect of MMP-1 on the myocardium, isolated adult rat myocytes were treated with active MMP-1, which caused injury and death of cultured myocytes, measured as lactate dehydrogenase release and trypan blue staining, in a dose- and time-dependent manner ( P < 0.05). Pretreatment with PD-166793, a specific MMP inhibitor, attenuated myocardial injury and death induced by active MMP-1. The present study for the first time shows that MMP-1 can directly cause myocyte injury or death and that attenuation of myocardial I/R injury by TGF-β1 may, at least partly, be mediated by the inhibition of upregulation of MMP-1.

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury

2004 ◽  
Vol 286 (5) ◽  
pp. H1923-H1935 ◽  
Author(s):  
James D. McCully ◽  
Hidetaka Wakiyama ◽  
Yng-Ju Hsieh ◽  
Mara Jones ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Parp Cleavage ◽  
Control Group ◽  
Early Reperfusion

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts ( n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately ( n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased ( P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased ( P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis ( P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

scholarly journals Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Wang ◽  
Xin Guo ◽  
Mingjie Zhou ◽  
Jichun Han ◽  
Bo Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Aqueous Extract ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE). The myocardial ischemia/reperfusion (I/R) injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP) and the maximum up/downrate of left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

scholarly journals Troxerutin Protects Against Myocardial Ischemia/Reperfusion Injury Via Pi3k/Akt Pathway in Rats

2017 ◽  
Vol 44 (5) ◽  
pp. 1939-1948 ◽  
Author(s):  
Liliang Shu ◽  
Wanzhe Zhang ◽  
Chen Huang ◽  
Gongcheng Huang ◽  
Gang Su
Keyword(s):  
Blood Pressure ◽  
Myocardial Ischemia ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Akt Pathway ◽  
Myocardial Infarct Size ◽  
Maximal Rate ◽  
Tnf Α ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Troxerutin, also known as vitamin P4, has been commonly used in the treatment of chronic venous insufficiency (CVI) disease. However, its effect on in vivo myocardial ischemia/reperfusion (I/R) injury, a model that closely mimics acute myocardial infarction in humans, is still unknown. Methods: The myocardial I/R injury rat model was created with troxerutin preconditioning. Myocardial infarct size was evaluated by the Evans blue-TTC method. Hemodynamic parameters, including the heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximal rate of rise in blood pressure in the ventricular chamber (+dp/dt max), and maximal rate of decline in blood pressure in the ventricular chamber (-dp/dt max) were monitored. Serum TNF-α and IL-10 were determined by ELISA kit. Cell apoptosis was detected by MTT method. Results: Troxerutin preconditioning significantly reduced myocardial infarct size, improved cardiac function, and decreased the levels of creatine kinase (CK), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) in the I/R injury rat model. The serum and mRNA levels of TNF-α and IL-10 as well as some apoptosis markers (Bax, Caspase 3) also decreased. Moreover, troxerutin pretreatment markedly increased the phosphorylation of Akt, and blocking PI3K activity by LY294002 abolished the protective effect of troxerutin on I/R injury. Conclusion: Troxerutin preconditioning protected against myocardial I/R injury via the PI3K/Akt pathway.

scholarly journals Cardioprotection against Ischemia/Reperfusion by Licochalcone B in Isolated Rat Hearts

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Jichun Han ◽  
Dong Wang ◽  
Bacui Yu ◽  
Yanming Wang ◽  
Huanhuan Ren ◽  
...  
Keyword(s):  
Infarct Size ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Cardiac Injury ◽  
Left Ventricular Pressure ◽  
Treated Group ◽  
Left Ventricular ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Triphenyltetrazolium Chloride

The generation of reactive oxygen species (ROS) is a major cause of heart injury induced by ischemia-reperfusion. The left ventricular developed pressure (LVDP) and the maximum up/down rate of left ventricular pressure (±dp/dtmax⁡) were documented by a physiological recorder. Myocardial infarct size was estimated macroscopically using 2,3,5-triphenyltetrazolium chloride staining. Coronary effluent was analyzed for lactate dehydrogenase (LDH) and creatine kinase (CK) release to assess the degree of cardiac injury. The levels of C-reactive protein (CRP), interleukin-8 (IL-8), tumor necrosis factor-α(TNF-α), and interleukin-6 (IL-6) were analyzed to determine the inflammation status of the myocardial tissue. Cardiomyocyte apoptosis analysis was performed using the In Situ Cell Death Detection Kit, POD. Accordingly, licochalcone B pretreatment improved the heart rate (HR), increased LVDP, and decreased CK and LDH levels in coronary flow. SOD level and GSH/GSSG ratio increased, whereas the levels of MDA, TNF-α, and CRP and activities of IL-8 and IL-6 decreased in licochalcone B-treated groups. The infarct size and cell apoptosis in hearts from licochalcone B-treated group were lower than those in hearts from the I/R control group. Therefore, the cardioprotective effects of licochalcone B may be attributed to its antioxidant, antiapoptotic, and anti-inflammatory activities.

Abstract 333: Deficiency of DJ-1 Leads to Increased Injury following Myocardial Ischemia by Enhancing Apoptosis and Oxidative Stress

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Jonathan P Lambert ◽  
Chad K Nicholson ◽  
John W Calvert
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Cellular Response ◽  
Troponin I ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Signaling Mechanism

Background: DJ-1 is a ubiquitously expressed protein that has typically been associated with the development of early onset Parkinson’s disease. Recent data suggests that it also plays a role in the cellular response to stress. Although much is known about DJ-1 in the brain, very little has been investigated in the heart. Here, we tested the hypothesis that a deficiency in DJ-1 would enhance myocardial ischemia-reperfusion (MI/R) injury. Methods and Results: Wild-type (WT) control and DJ-1 knockout (DJ-1 KO) mice were subjected to 45 min of left coronary artery ischemia followed by 24 hrs of reperfusion. The deficiency of DJ-1 significantly increased myocardial infarct size relative to both the area-at-risk and entire left ventricle, as well as increased circulating troponin-I levels (Panels A-B). Echocardiography and hemodynamic analysis at 1 week of reperfusion revealed that DJ-1 KO mice experienced greater left ventricular dilatation and hypertrophy, displayed exacerbated left ventricular dysfunction, and displayed worse contractility and relaxation when compared to WT controls. In an effort to evaluate the signaling mechanism responsible for the increased injury in DJ-1 KO mice, additional WT and KO animals were subjected to 45 min of ischemia followed by 4 hrs of reperfusion. DJ-1 KO hearts were found to display higher levels of oxidative stress, greater caspase-3 activity (Panel C), enhanced phosphorylation of Jnk, and enhanced activation of the mitochondrial fission protein, dynamin-related protein 1 (Drp1). Conclusions: These findings provide important information that DJ-1 plays a protective role in heart against acute MI/R injury.

scholarly journals The Antioxidant, Anti-Inflammatory and Anti-Apoptotic Activities of the Bauhinia Championii Flavone are Connected with Protection Against Myocardial Ischemia/Reperfusion Injury

2016 ◽  
Vol 38 (4) ◽  
pp. 1365-1375 ◽  
Author(s):  
Jie Jian ◽  
Feifei Xuan ◽  
Feizhang Qin ◽  
Renbin Huang
Keyword(s):  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background/Aims: Previous studies have demonstrated that Bauhinia championii flavone (BCF) exhibits anti-oxidative, anti-hypoxic and anti-stress properties. This study was designed to investigate whether BCF has a cardioprotective effect against myocardial ischemia/reperfusion (I/R) injuries in rats and to shed light on its possible mechanism. Methods: The model of I/R was established by ligating the left anterior descending coronary artery for 30 min, then reperfusing for 180 min. Hemodynamic changes were continuously monitored. The content of malondialdehyde (MDA) as well as the lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities were assessed. The release of interleukin-6 (IL-6) was measured by enzyme-linked immunosorbent assay (ELISA). Apoptosis of cardiomyocytes was determined by caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression of TLR4, NF-κBp65, Bcl-2 and Bax were detected by western blotting. Results: Pretreatment with BCF significantly reduced the serum levels of LDH, MDA and IL-6, but increased the activities of SOD and GSH-Px. It also attenuated myocardial infarct size, reduced the apoptosis rate and preserved cardiac function. Furthermore, BCF inhibited caspase-3 activity and the expression of TLR4, phosphorylated NF-κBp65 and Bax, but enhanced the expression of Bcl-2. Conclusion: These results provide substantial evidence that BCF exerts a protective effect on myocardial I/R injury, which may be attributed to attenuating lipid peroxidation, the inflammatory response and apoptosis.

scholarly journals The cardioprotective effect of intralipid in decreasing the ischemic insults during off-pump coronary artery revascularization

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maha Sadek El Derh ◽  
Samar Mohamed Abdel Twab ◽  
Mohamed Elgouhary
Keyword(s):  
Coronary Artery ◽  
Cardiac Index ◽  
Reperfusion Injury ◽  
Troponin I ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Off Pump ◽  
Coronary Artery Revascularization

Abstract Background Off pump coronary artery revascularization (OPCAB) surgeries have benefits over the conventional on pump cardiac surgery, because it avoids the trauma caused by cardiopulmonary bypass (CPB) and minimize aortic manipulation. However, some disadvantages of OPCAB include the concern of ineffective coronary revascularization. Some drugs have shown the ability to protect the myocardium in different studies, by different methods. The usage of intralipid has been shown to make a better functional recovery of the cardiac muscles and help to decrease the myocardial infarct size, it shortens the action potential time, which show polyunsaturated fatty acids diets mechanism as an antiarrhythmic drug, and are associated with low incidence of coronary artery disease. Methods We divided patients into two groups according to the randomization envelopes: intralipid group (group A) received 1.5 ml/kg intralipid 20% through central venous line after sternotomy over 1 h and during infusion, blood pressure, heart rate, and temperature were monitored all through the infusion time. Control group (group B) received normal saline 0.9% in the same volume over the same duration. Results This study showed that infusion of 1.5 ml/kg intralipid after sternotomy in off pump coronary artery revascularization given as preconditioning agent improve the myocardial ischemia reperfusion injury, decrease the need for high doses of nor adrenaline infusion after revascularization, earlier normalization in troponin levels starting 24 h after surgery and higher values of cardiac index were measured in ICU using PICCO. Conclusions This study showed the benefits of infusion of 1.5 ml/kg of intralipid after sternotomy, in preconditioning during OPCABG. Preconditioning with intralipid proved to decrease reperfusion injury in myocardium expressed by improvement in cardiac functions (EF and cardiac index) and normalization of specific cardiac marker (cardiac troponin I).

Abstract 145: Apelin Reduces Myocardial Infarction Size and Promotes Angiogenesis by Increasing SDF-1/CXCR4 and AKT/eNOS/VEGF Pathways

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Lanfang Li ◽  
Heng Zeng ◽  
Jian-xiong Chen
Keyword(s):  
Myocardial Infarction ◽  
Myocardial Ischemia ◽  
Molecular Mechanisms ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Border Zone ◽  
Heart Weight ◽  
Tunel Staining ◽  
Myocardial Infarct Size

Background: Apelin is an endogenous ligand for the angiotensin-like 1 receptor (APJ) and is emerging as a key player in the regulation of angiogenesis as well as ischemia/reperfusion injury. So far, little is known about the functional role of apelin in myocardial ischemia. We investigated the potential intracellular molecular mechanisms and protective role of apelin during myocardial ischemic injury. Methods and Results: Myocardial ischemia was achieved by ligation of the left anterior descending coronary artery (LAD) for 24 hours and 14 days. Myocardial apoptosis was detected by TUNEL staining. Akt, endothelial nitric oxide synthase (eNOS), vascular endothelial growth factor (VEGF), SDF-1 and CXCR4 expression were measured by western blot. The CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells were determined by immunostaining. Myocardial capillary and arteriole densities were analyzed in the border zone of infarcted myocardium at 14 d of ischemia. Treatment of C57BL/6J mice with apelin-13 (1 mg/Kg.d) by i.p. injection for 3 days before surgery results in significant decreases in TUNEL positive cells and myocardial infarct size at 24 hours of ischemia. Treatment with apelin increases the phosphorylation of AKT and eNOS and upregulates VEGF expression in the ischemic heart. Furthermore, treatment with apelin leads to the expression of SDF-1 and CXCR4 and increases in the number of CD133+/cKit+/Sca1+, CD133/SDF-1+ and cKit/CXCR4+ cells in ischemic hearts. Treatment with apelin also significantly increases myocardial capillary densities and arteriole formation together with a significant decrease in the ratio of heart weight to body weight at 14 days of ischemia. This is accompanied by a significant improvement of cardiac function after 14 days of ischemia. Conclusions: Our data demonstrate that apelin contributes to the protection of myocardial infarction and angiogenesis by the mechanisms involving in upregulation of SDF-1/CXCR4 and AKT/eNOS/VEGF pathways.

Abstract 16381: Novel Thiol-activated H2S Donors Attenuate Myocardial Ischemia/Reperfusion Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Chelsea Organ ◽  
Zhen Li ◽  
Yu Zhao ◽  
Chuntao Yang ◽  
Shashi Bhushan ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Sustained Release ◽  
Murine Model ◽  
Troponin I ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Myocardial Ischemia Reperfusion

Background: Hydrogen sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, improving mitochondrial function, and attenuating apoptosis. One of the major limitations of currently available H2S donors is poor pharmacokinetics profiles that result in very rapid and uncontrolled H2S release. NSHD-1 and NSHD-2 are recently developed thiol-activated H2S donors designed for sustained release of H2S upon activation by molecules containing thiol groups such as cysteine and glutathione. We hypothesized that these novel H2S donors would generate H2S for extended periods and ameliorate myocardial cell death following MI/R in an in vivo murine model. Methods and Results: C57BL6/J male mice (10-12 weeks of age) were subjected to 45 minutes of MI followed by 24 hours of R. At the time of reperfusion, animals received Vehicle (0.5% THF), NSHD-1 (50 μg/kg and 100 μg/kg), or NSHD-2 (50 μg/kg) by direct intracardiac (i.c.) injection. In addition, at 4 hours of R, plasma was collected for troponin-I measurements. In preliminary studies we observed sustained release of H2S with both of these H2S donors. Myocardial infarct size was reduced by 35% (p < 0.01 vs. Vehicle) in mice treated with NSHD-1 (100 μg/kg), 43% (p < 0.05 vs. Vehicle) in mice treated with NSHD-2 (50 μg/kg), and 54% (p < 0.01 vs. Vehicle) in mice treated with NSHD-2 (100 μg/kg). Conclusions: NSHD-1 and NSHD-2 significantly attenuate MI/R injury in a murine model. Experiments are currently underway to further define the in vivo pharmacokinetics of H2S release from these agents, mechanisms of action, and safety profile.

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