Hydrogen sulfide (H2S) exhibits protective effects in cardiovascular disease such as myocardial ischemia/reperfusion (I/R) injury, cardiac hypertrophy, and atherosclerosis. Despite these findings, its mechanism of action remains elusive. Recent studies suggest that H2S can modulate protein activity through redox-based post-translational modifications of protein cysteine residues forming hydropersulfides (RSSH). Furthermore, emerging evidence indicates that reactive sulfur species, including RSSH and polysulfides, exhibit cardioprotective action. However, it is not clear yet whether there are any pharmacological differences in the use of H2S vs. RSSH and/or polysulfides. This study aims to examine the differing cardioprotective effects of distinct reactive sulfur species (RSS) such as H2S, RSSH, and dialkyl trisulfides (RSSSR) compared with canonical ischemic post-conditioning in the context of a Langendorff ex-vivo myocardial I/R injury model. For the first time, a side-by-side study has revealed that exogenous RSSH donation is a superior approach to maintain post-ischemic function and limit infarct size when compared with other RSS and mechanical post-conditioning. Our results also suggest that RSSH preserves mitochondrial respiration in H9c2 cardiomyocytes exposed to hypoxia-reoxygenation via inhibition of oxidative phosphorylation while preserving cell viability.
BACKGROUND: Growing evidence suggests that piriform cortex resection during anterior temporal lobectomy is important for achieving good seizure outcome in mesial temporal lobe epilepsy (mTLE). However, the relationship between seizure outcome and piriform cortex ablation during MR-guided laser interstitial thermal therapy (MRgLITT) remains unclear. OBJECTIVE: To determine whether ablation of piriform cortex was associated with seizure outcome in patients with mTLE undergoing MRgLITT. METHODS: We performed preablation and postablation volumetric analyses of hippocampus, amygdala, piriform cortex, and ablation volumes in patients with mTLE who underwent MRgLITT at our institution from 2014 to 2019. RESULTS: Thirty nine patients with mTLE were analyzed. In univariate logistic regression, percent piriform cortex ablation was associated with International League Against Epilepsy (ILAE) class 1 at 6 months (odds ratio [OR] 1.051, 95% CI [1.001-1.117], P = .045), whereas ablation volume, percent amygdala ablation, and percent hippocampus ablation were not (P > .05). At 1 year, ablation volume was associated with ILAE class 1 (OR 1.608, 95% CI [1.071-2.571], P = .021) while percent piriform cortex ablation became a trend (OR 1.050, 95% CI [0.994-1.109], P = .054), and both percent hippocampus ablation and percent amygdala ablation were not significantly associated with ILAE class 1 (P > .05). In multivariable logistic regression, only percent piriform cortex ablation was a significant predictor of seizure freedom at 6 months (OR 1.085,], P = .019) and at 1 year (OR 1.074, 95% CI [1.003-1.178], P = .041). CONCLUSION: Piriform cortex ablation volume is associated with seizure outcome in patients with mTLE undergoing MRgLITT. The piriform cortex should be considered a high yield ablation target to achieve good seizure outcome.
OBJECTIVE Maximal safe ablation of target structures during magnetic resonance–guided laser interstitial thermal therapy (MRgLiTT) is critical to achieving good seizure outcome in patients with mesial temporal lobe epilepsy (mTLE). The authors sought to determine whether intraoperative physiological variables are associated with ablation volume during MRgLiTT. METHODS Patients with mTLE who underwent MRgLiTT at our institution from 2014 to 2019 were retrospectively analyzed. Ablation volume was determined with volumetric analysis of intraoperative postablation MR images. Physiological parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], end-tidal carbon dioxide [ETCO2]) measured 40 minutes prior to ablation were analyzed. Univariate and multivariate regression analyses were performed to determine independent predictors of ablation volume. RESULTS Forty-four patients met the inclusion criteria. The median (interquartile range) ablation volume was 4.27 (2.92–5.89) cm3, and median ablation energy was 7216 (6402–8784) J. The median MAP, SBP, DBP, and ETCO2 values measured during the 40-minute period leading up to ablation were 72.8 (66.2–81.5) mm Hg, 104.4 (96.4–114.4) mm Hg, 62.4 (54.1–69.8) mm Hg, and 34.1 (32.0–36.2) mm Hg, respectively. In univariate analysis, only total laser energy (r = 0.464, p = 0.003) and 40-minute average ETCO2 (r = −0.388, p = 0.012) were significantly associated with ablation volume. In multivariate analysis, only ETCO2 ≤ 33 mm Hg (p = 0.001) was significantly associated with ablation volume. CONCLUSIONS Total ablation energy and ETCO2, but not blood pressure, may significantly affect ablation volume in mTLE patients undergoing MRgLiTT. Mild hypocapnia was associated with increased extent of ablation. Intraoperative monitoring and modulation of ETCO2 may help improve extent of ablation, prediction of ablation volume, and potentially seizure outcome.
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