RESUMEN
Hydrogen sulfide (H2S), an ambient air pollutant, has been reported to increase cardiac events in patients with cardiovascular diseases, but the underlying mechanisms remain not elucidated. This study investigated the pro-arrhythmic effects of H2S in healthy and ischemic conditions. Experimental data of H2S effects on ionic channels (including the L-type Ca2+ channel and ATP-sensitive K+ channel) were incorporated into a virtual heart model to evaluate their integral action on cardiac arrhythmogenesis. It was shown that H2S depressed cellular excitability, abbreviated action potential duration, and augmented tissue's transmural dispersion of repolarization, resulting in an increase in tissue susceptibility to initiation and maintenance of reentry. The observed effects of H2S on cardiac excitation are more remarkable in the ischemic condition than in the healthy condition. This study provides mechanistic insights into the pro-arrhythmic effects of air pollution (H2S), especially in the case with extant ischemic conditions.
RESUMEN
The endocannabinoid system (ECS) is a potential pharmaceutical target for the treatment of inflammatory bowel diseases (IBDs). The aim of this study was to explore the effects of activation of the ECS on IBD and the associated neural inflammation-induced disruption of the blood-brain barrier (BBB). In a mouse model of trinitrobenzene sulfonic acid-induced colitis, the inhibition of fatty acid amide hydrolase with URB597 elevated the arachidonoylethanolamide concentration of the colon. Macroscopic alterations of the colons were evaluated, and the 7-day survival rate of mice was analyzed. BBB integrity was assessed using a dye tracer method, and the cognitive function of mice was examined using a fear-conditioning test. URB597 treatment significantly reduced macroscopic alterations of the colon, decreased the mortality rate, and protected the integrity of the BBB in the mice (P<0.05). No significant changes were observed in the cognitive functions of the mice (P>0.05); therefore, the neuroprotective effect of ECS in this colitis model requires further investigation. Activation of the ECS was efficient in ameliorating colitis and increasing the survival rate of the mice, and reducing remote organ changes induced by colitis. The results suggest that modulation of the ECS is a potential therapeutic approach for IBDs and the associated remote organ lesions.