RESUMO
OBJECTIVE: The primary objective of this study was to evaluate the protective effect of taurine on endothelial dysfunction in a vascular ischemia-reperfusion (IR) model. METHODS: Thoracic aortas of 9 male Sprague-Dawley rats (350-500 g) were cut into rings and randomized into control (n = 7), IR (n = 8), IR + taurine 1 mM (n = 7), IR + taurine 10 mM (n = 8), IR + taurine 30 mM (n = 8), and IR + taurine 100 mM (n = 5) groups. Aortic rings in the IR group were stored in 0.9% saline at 4 °C for 24 h, placed in Krebs-Henseleit solution gassed with 95%O2 + 5%CO2 at 37 °C, and exposed to sodium hypochlorite (200 µM) for 30 min. Responses to KCl (80 mM), phenylephrine (10-10-10-4 M), acetylcholine (10-10-10-4 M), and sodium nitroprusside (SNP, 10-11-10-5 M) were recorded. Emax (maximum response) and pD2 (negative logarithm of concentration producing half-maximum response) were calculated. RESULTS: IR decreased KCl contraction (control 1047 ± 176 mg, IR 682 ± 128 mg, p = 0.0007), which was reversed by 30 and 100 mM taurine (960 ± 313 mg, p = 0.02 and 1066 ± 488 mg, p = 0.02, respectively). IR impaired phenylephrine, acetylcholine, and SNP responses (p < 0.0001). Taurine did not affect IR-impaired phenylephrine contractions. IR decreased both pD2 (control, 7.1 ± 0.1; IR, 6.0 ± 0.2; p < 0.01) and Emax (control, 83.5 ± 2.7%; IR, 26.8 ± 2.5%; p < 0.0001) of acetylcholine relaxation, both of which were reversed by 100 mM taurine (pD2, 7.2 ± 0.1; p < 0.001; Emax, 45.4 ± 2.6%; p < 0.0001). For SNP relaxation, IR decreased pD2 (control 8.2 ± 0.1, IR 7.7 ± 0.1, p < 0.01), which was reversed by 100 mM taurine (8.5 ± 0.1, p < 0.0001). CONCLUSION: Taurine protects endothelial function after IR injury. Further studies should explore the mechanism of this effect and the potential of adding taurine to vascular graft storage solutions.
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.
