Therapeutic delivery of hydrogen sulfide for salvage of ischemic skeletal muscle after the onset of critical ischemia

Henderson, Peter W.; Jimenez, Natalia; Ruffino, John; Sohn, Allie M.; Weinstein, Andrew L.; Krijgh, David D.; Reiffel, Alyssa J.; Spector, Jason A.

doi:10.1016/j.jvs.2010.10.094

Cited by 30 publications

(33 citation statements)

References 33 publications

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“…protection from ischemia/reperfusion injury has been demonstrated in a number of extracardiac organs, including the kidney (171), which presumably offsets the reduction in endogenous H 2 S production (192), liver and small intestine (52,198), skeletal muscle (49,51), and cellular components of cutaneous tissue (50). As in the vasculature, H 2 S has been proposed to combine with NO to produce a nitrosothiol with inotropic properties (195,194).…”

Section: R301 Therapeutic Potential Of H2smentioning

confidence: 99%

The therapeutic potential of hydrogen sulfide: separating hype from hope

Olson

2011

American Journal of Physiology-Regulatory, Integrative and Comp

163

154

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Hydrogen sulfide (H2S) has become the hot new signaling molecule that seemingly affects all organ systems and biological processes in which it has been investigated. It has also been shown to have both proinflammatory and anti-inflammatory actions and proapoptotic and anti-apoptotic effects and has even been reported to induce a hypometabolic state (suspended animation) in a few vertebrates. The exuberance over potential clinical applications of natural and synthetic H2S-“donating” compounds is understandable and a number of these function-targeted drugs have been developed and show clinical promise. However, the concentration of H2S in tissues and blood, as well as the intrinsic factors that affect these levels, has not been resolved, and it is imperative to address these points to distinguish between the physiological, pharmacological, and toxicological effects of this molecule. This review will provide an overview of H2S metabolism, a summary of many of its reported “physiological” actions, and it will discuss the recent development of a number of H2S-donating drugs that show clinical potential. It will also examine some of the misconceptions of H2S chemistry that have appeared in the literature and attempt to realign the definition of “physiological” H2S concentrations upon which much of this exuberance has been established.

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Section: R301 Therapeutic Potential Of H2smentioning

confidence: 99%

The therapeutic potential of hydrogen sulfide: separating hype from hope

Olson

2011

American Journal of Physiology-Regulatory, Integrative and Comp

163

154

View full text Add to dashboard Cite

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“…This effect was reversible and apparently without long-term neurological consequences. Because of its ability to lower metabolism and body temperature, H 2 S is now being investigated as providing protection against hypoxia and ischemia, for example, in brain (Holzer, 2010) and kidneys and liver (Henderson et al, 2011). Other therapeutic applications stem from H 2 S's role as a smooth muscle relaxant and neurological signaling molecule (Kimura, 2002;Wang, 2003;Wagner et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Is Hydrogen Sulfide-Induced Suspended Animation General Anesthesia?

McKinstry²,

Moore³

et al. 2012

J Pharmacol Exp Ther

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Hydrogen sulfide (H 2 S) depresses mitochondrial function and thereby metabolic rates in mice, purportedly resulting in a state of "suspended animation." Volatile anesthetics also depress mitochondrial function, an effect that may contribute to their anesthetic properties. In this study, we ask whether H 2 S has general anesthetic properties, and by extension, whether mitochondrial effects underlie the state of anesthesia. We compared loss of righting reflex, electroencephalography, and electromyography in mice exposed to metabolically equipotent concentrations of halothane, isoflurane, sevoflurane, and H 2 S. We also studied combinations of H 2 S and anesthetics to assess additivity. Finally, the long-term effects of H 2 S were assessed by using the Morris water maze behavioral testing 2 to 3 weeks after exposures. Exposure to H 2 S decreases O 2 consumption, CO 2 production, and body temperature similarly to that of the general anesthetics, but fails to produce a loss of righting reflex or muscle atonia at metabolically equivalent concentrations. When combined, H 2 S antagonizes the metabolic effects of isoflurane, but potentiates the isoflurane-induced loss of righting reflex. We found no effect of prior H 2 S exposure on memory or learning. H 2 S (250 ppm), not itself lethal, produced delayed lethality when combined with subanesthetic concentrations of isoflurane. H 2 S cannot be considered a general anesthetic, despite similar metabolic suppression. Metabolic suppression, presumably via mitochondrial actions, is not sufficient to account for the hypnotic or immobilizing components of the anesthetic state. Combinations of H 2 S and isoflurane can be lethal, suggesting extreme care in the combination of these gases in clinical situations.

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“…Its incidence may be as high as 13-17 cases per 100.000 people per year and mortality rates may reach 18% in some series 12 . Due to the high metabolic demand of skeletal muscle, irreversible damage may occur when perfusion occurs even after brief ischemic intervals 7,13 . In this regard, the soleus muscle is particularly sensitive to ischemia due to its metabolism 14 .…”

Section: Discussionmentioning

confidence: 99%

“…Skeletal muscles are the predominant tissue damaged in this situation, with high vulnerability to cell death due to ischemia. Typically, severe injury in skeletal musculature starts after a 2-hours ischemic interval 1,7 . However, irreversible muscle cell damage seems to start after three hours of ischemia and to be nearly complete after a 6-hours interval 8 .…”

Section: Ischemia-reperfusion Injury (Iri) In Skeletal Musclementioning

confidence: 99%

Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

Armstrong

Figueiredo³

et al. 2013

Acta Cir. Bras.

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PURPOSE:To investigate the effect of sildenafil citrate (SC) on skeletal muscle ischemia-reperfusion (IR) injury in rats. METHODS:Adult male Wistar rats were randomized into three groups: vehicle-treated control (CTG), sildenafil citrate-treated (SCG), and sham group (SG). CTG and SCG had femoral artery occluded for 6 hours. Saline or 1 mg/kg of SC was given 5.5 hours after occlusion. SG had a similar procedure without artery occlusion. Soleus muscle samples were acquired 4 or 24h after the reperfusion.Immunohistochemistry caspase-3 analysis was used to estimate apoptosis using the apoptotic ratio (computed as positive/negative cells). Wilcoxon rank-sum or Kruskal-Wallis tests were used to assess differences among groups. RESULTS:Eighteen animals were included in the 4h reperfusion groups and 21 animals in the 24h reperfusion groups. The mean apoptotic ratio was 0.18±0.1 for the total cohort; 0.14±0.06 for the 4h reperfusion groups and 0.19±0.08 for the 24h groups (p<0.05).The SCG had lower caspase-3 ratio compared to the control groups at the 24h reperfusion time point (p<0.05). CONCLUSION:Sildenafil citrate administration after the onset of the ischemic injury reduces IR-induced cellular damage in skeletal muscle in this rat hindlimb ischemia model. Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury.Immunohistochemical study in rat model

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Therapeutic delivery of hydrogen sulfide for salvage of ischemic skeletal muscle after the onset of critical ischemia

Cited by 30 publications

References 33 publications

The therapeutic potential of hydrogen sulfide: separating hype from hope

The therapeutic potential of hydrogen sulfide: separating hype from hope

Is Hydrogen Sulfide-Induced Suspended Animation General Anesthesia?

Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury: immunohistochemical study in rat model

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