RESUMO
Hydrogen sulfide (H2S) is a gasotransmitter that has been studied for its potential therapeutic effects, including its role in the pathophysiology and treatment of stroke. This systematic review and meta-analysis aimed to determine the sufficiency of overall preclinical evidence to guide the initiation of clinical stroke trials with H2S and provide tailored recommendations for their design. PubMed, Web of Science, Scopus, EMBASE, and MEDLINE were searched for studies evaluating the effect of any H2S donor on in vivo animal models of regional ischemic stroke, and 34 publications were identified. Pooling of the effect sizes using the random-effect model revealed that H2S decreased the infarct area by 34.5% (95% confidence interval (CI) 28.2-40.8%, p < 0.0001), with substantial variability among the studies (I2 = 89.8%). H2S also caused a 37.9% reduction in the neurological deficit score (95% CI 29.0-46.8%, p < 0.0001, I2 = 63.8%) and in the brain water content (3.2%, 95% CI 1.4-4.9%, p = 0.0014, I2 = 94.6%). Overall, the studies had a high risk of bias and low quality of evidence (median quality score 5/15, interquartile range 4-9). The majority of the included studies had a "high" or "unclear" risk of bias, and none of the studies overall had a "low" risk. In conclusion, H2S significantly improves structural and functional outcomes in in vivo animal models of ischemic stroke. However, the level of evidence from preclinical studies is not sufficient to proceed to clinical trials due to the low external validity, high risk of bias, and variable design of existing animal studies.
RESUMO
Introduction: The in vitro rat vascular ischaemia and reperfusion model is used to evaluate the molecular and functional effects of potential agents against ischaemia and reperfusion injury of autologous graft veins. However, there is no consensus on whether hypoxia, rather than ischaemia, is sufficient to induce vascular dysfunction. Aim: To compare the effects of hypoxia and ischaemia, with or without reperfusion, on the vascular functions of isolated thoracic aortic rings of rats. Material and methods: Thoracic aortas of 12 male Sprague-Dawley rats (350-500 g, 18-24 months old) were isolated and divided into rings that were randomly allocated to control, ischaemia, hypoxia, ischaemia-reperfusion, and hypoxia-reperfusion groups. Aortic rings other than those of the control group were stored at 4°C for 24 h in saline. For ischaemia, saline was gassed with nitrogen. After 24 h, aortic rings in the ischaemia-reperfusion and hypoxia-reperfusion groups were incubated with 200 µM sodium hypochlorite for 30 min. Vascular and endothelial functions were tested in an organ bath set-up. Results: Vascular response to potassium chloride (80 mM) decreased in all experimental groups compared to the control group (p = 0.007), but phenylephrine-induced contraction (10-5 M) increased only in the ischaemia-reperfusion group (p < 0.0001). Acetylcholine (10-11-10-5 M)-induced endothelium-dependent vasorelaxations were impaired in all groups - particularly in the ischaemia-reperfusion group (p = 0.0011). Sodium nitroprusside (10-12-10-7 M)-induced endothelium-independent vasorelaxations were similar across all groups (p = 0.1258). Conclusions: Ischaemia followed by reperfusion should be implanted to achieve maximum endothelial and contractile dysfunction in vitro, and to replicate ischaemia and reperfusion injury of autologous graft veins.
RESUMO
Hydrogen sulfide (H2S) has been shown to be effective against kidney ischemia-reperfusion injury (IRI) in animal studies. We aimed to evaluate the current evidence from in vivo animal studies for the protective effects of H2S against kidney IRI by systematically reviewing the literature and performing a meta-analysis. Based on the preregistered protocol (PROSPERO: CRD42021295469); PubMed, Medline, Embase, Web of Science, and Scopus were searched to identify in vivo animal studies evaluating the effect of H2S against kidney IRI. Standardized mean difference (SMD) with 95% confidence interval (CI) was calculated and pooled using random-effects meta-analysis. Twenty-two articles complied with eligibility criteria, from which the creatinine levels of 152 control animals and 182 animals treated with H2S from 27 individual experiments were pooled. H2S treatment significantly decreased serum creatinine (SMD = -1.82 [95% CI -1.12, -2.51], p < 0.0001), blood urea nitrogen (-2.50 [-1.46, -3.54], p < 0.0001), tissue malondialdehyde (-2.59 [-3.30, -1.88], p < 0.0001), tunel positive cells (-3.16 [-4.38, -1.94], p < 0.0001), and tubular damage score (-2.01 [-3.03, -0.99], p < 0.0001). There was a high heterogeneity across studies (I2 = 83.5% for serum creatinine level). In meta-regression analysis, the type of H2S donor and its application time accounted for 11.3% (p = 0.025) and 16.6% (p = 0.039) of heterogeneity, respectively. Accordingly, H2S protects the kidney against IRI only if it is given as GYY4137 before or during ischemia. Although H2S is a potential candidate against kidney IRI, further well-designed preclinical studies focusing on GYY4137 are warranted before clinical implication.