Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial

Koning, M.W.A. de; Dorp, Paulien van; Assa, Solmaz; Hartman, Minke H. T.; Voskuil, Michiel; Anthonio, Rutger L.; Veen, Duco; Prado, G Pundziute-Do; Leiner, Tim; Goor, Harry van; Meer, Peter van der; Veldhuisen, Dirk J. van; Nijveldt, Robin; Lipšic, Erik; Harst, Pim van der

doi:10.1016/j.ahj.2021.08.012

Cited by 14 publications

(11 citation statements)

References 47 publications

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“…These effects were accompanied by an increase in endogenous H 2 S, which was suggested to be responsible for the therapeutic effects. Recently, a clinical trial in the Netherlands examined the effects of administering STS to patients presenting with ST-segment elevation myocardial infarction prior to restoring perfusion through percutaneous coronary intervention [ 89 ]. Unfortunately, the researchers observed no effect of the STS treatment on infarct size, leading to the discontinuation of the trial [ 90 ].…”

Section: Sodium Thiosulfate: a Clinically Viable H 2 ...mentioning

confidence: 99%

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs

McFarlane

Nelson

Dugbartey

et al. 2023

IJMS

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Ischemia-reperfusion injury (IRI), a pathological condition resulting from prolonged cessation and subsequent restoration of blood flow to a tissue, is an inevitable consequence of solid organ transplantation. Current organ preservation strategies, such as static cold storage (SCS), are aimed at reducing IRI. However, prolonged SCS exacerbates IRI. Recent research has examined pre-treatment approaches to more effectively attenuate IRI. Hydrogen sulfide (H2S), the third established member of a family of gaseous signaling molecules, has been shown to target the pathophysiology of IRI and thus appears to be a viable candidate that can overcome the transplant surgeon’s enemy. This review discusses pre-treatment of renal grafts and other transplantable organs with H2S to mitigate transplantation-induced IRI in animal models of transplantation. In addition, ethical principles of pre-treatment and potential applications of H2S pre-treatment in the prevention of other IRI-associated conditions are discussed.

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Section: Sodium Thiosulfate: a Clinically Viable H 2 ...mentioning

confidence: 99%

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs

McFarlane

Nelson

Dugbartey

et al. 2023

IJMS

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“…No serious adverse events were observed [74]. The same group will investigate the potential benefit of an intervention Na 2 S 2 O 3 in a follow-up double-blind, randomized, placebo-controlled, multicenter trial (GIPS-IV), with a planned enrollment of 380 patients with ST-elevation myocardial infarction (STEMI) [75]. Patients will receive 12.5 g Na 2 S 2 O 3 directly after admission and a second dose 6 h later.…”

Section: Clinical Perspectivementioning

confidence: 99%

“…Patients will receive 12.5 g Na 2 S 2 O 3 directly after admission and a second dose 6 h later. The primary endpoint is myocardial infarct size after 4 months; secondary endpoints include the effects of Na 2 S 2 O 3 on peak CK-MB (creatine kinase muscle brain type, as an early measure of MI) during admission and left ventricular ejection fraction and NT-proBNP (N terminal pro brain natriuretic peptide, as a measure of heart insufficiency) levels at 4 months follow-up [75]. The group expects first results on the primary endpoint soon ("Q1 2022"), but no updates have been published yet.…”

Section: Clinical Perspectivementioning

confidence: 99%

H2S in Critical Illness—A New Horizon for Sodium Thiosulfate?

et al. 2022

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Ever since the discovery of endogenous H2S and the identification of its cytoprotective properties, efforts have been made to develop strategies to use H2S as a therapeutic agent. The ability of H2S to regulate vascular tone, inflammation, oxidative stress, and apoptosis might be particularly useful in the therapeutic management of critical illness. However, neither the inhalation of gaseous H2S, nor the administration of inorganic H2S-releasing salts or slow-releasing H2S-donors are feasible for clinical use. Na2S2O3 is a clinically approved compound with a good safety profile and is able to release H2S, in particular under hypoxic conditions. Pre-clinical studies show promise for Na2S2O3 in the acute management of critical illness. A current clinical trial is investigating the therapeutic potential for Na2S2O3 in myocardial infarct. Pre-eclampsia and COVID-19 pneumonia might be relevant targets for future clinical trials.

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“…Sodium thiosulfate (STS) has been used to deal with calciphylaxis in clinic and provided potential opportunity against various ectopic calcification including VC. − Findings from experimental studies suggested that STS attenuated VC possibly due to its potent chelating and antioxidant properties. , However, recent clinical evidence from GIPS-IV study reported that STS did not improve cardiovascular outcomes in patients with myocardial infarction because most patients can not tolerate high doses of STS due to offensively strong odor and adverse reactions such as nausea and vomiting . In addition, traditional systemic administration of STS has been associated with severe adverse effects in normal organs due to undesirable accumulation in normal tissues such as the reduction of bone mineral density. , Moreover, only a small fraction of STS could actually reach the site of VC .…”

Section: Introductionmentioning

confidence: 99%

“… 13 , 14 However, recent clinical evidence from GIPS-IV study reported that STS did not improve cardiovascular outcomes in patients with myocardial infarction 15 because most patients can not tolerate high doses of STS due to offensively strong odor and adverse reactions such as nausea and vomiting. 15 In addition, traditional systemic administration of STS has been associated with severe adverse effects in normal organs due to undesirable accumulation in normal tissues such as the reduction of bone mineral density. 13 , 16 Moreover, only a small fraction of STS could actually reach the site of VC.…”

Section: Introductionmentioning

confidence: 99%

Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate against Vascular Calcification

Feng,

Teng,

Zhong

et al. 2023

ACS Nano

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As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. In vitro , the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.

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Rationale and Design of the Groningen Intervention Study for the Preservation of Cardiac Function with Sodium Thiosulfate after St-segment Elevation Myocardial Infarction (GIPS-IV) trial

Cited by 14 publications

References 47 publications

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs

Pre-Treatment of Transplant Donors with Hydrogen Sulfide to Protect against Warm and Cold Ischemia-Reperfusion Injury in Kidney and Other Transplantable Solid Organs

H2S in Critical Illness—A New Horizon for Sodium Thiosulfate?

Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate against Vascular Calcification

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