Hirudin ameliorates myocardial ischemia-reperfusion injury in a rat model of hemorrhagic shock and resuscitation: roles of NLRP3-signaling pathway.

Severe hemorrhage shock and resuscitation (HSR) has been reported to induce myocardial ischemia-reperfusion injury (MIRI), resulting in a poor prognosis. Hirudin, an effective thrombin inhibitor, can offer protection against MIRI. This study aimed to determine if hirudin administration ameliorates HSR-induced MIRI and the underlying mechanism. A rat model of HSR was established by bleeding rats to a mean arterial blood pressure of 30-35 mmHg for 45 min and then resuscitating them with all the shed blood through the left femoral vein. After HSR, 1 mg/kg of hirudin was administrated immediately. At 24 h after HSR, the cardiac injury was assessed using serum CK-MB, cTnT, hematoxylin-eosin (HE) staining, echocardiography, M1-polarized macrophages, and pyroptosis-associated factors, including cleaved caspase-1, Gasdermin D (GSDMD) N-terminal, IL-1ß, and IL-18 were measured by immunofluorescence and western blot assays. Nigericin, a unique agonist, was utilized to evaluate the responsibilities of NLRP3 signaling. Under the HSR condition, rats exhibited a significant increase in myocardial injury score, an elevation of serum cTnT, CK-MB levels, an aggrandization of M1-polarized macrophages, an upregulation of pyroptosis-associated factors, including cleaved caspase-1, GSDMD N-terminal, IL-1ß, and IL-18, but a significant decrease in left ventricular ejection fraction (EF%) and a reduction of left ventricular fractional shortening (FS%), while hirudin administration partially restored the changes. However, the NLRP3 agonist nigericin reversed the cardioprotective effects of hirudin. We determined the cardioprotective effects of hirudin against HSR-induced MIRI. The mechanism may involve the inhibition of NLRP3-induced pyroptosis.

Effect of Oxycodone hydrochloride combined with Dexmedetomidine on quality of recovery and stress response after general anesthesia in patients who had Laparoscopic Cholecystectomy.

OBJECTIVE: To explore the effect of oxycodone hydrochloride combined with dexmedetomidine on the recovery quality and stress response during anesthesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS: Ninety patients who had LC in Cangzhou Hospital of Integrated TCM-WM of Hebei from December 2016 to December 2019 were selected and divided into dexmedetomidine group (DEX group), oxycodone hydrochloride group (Q group), dexmedetomidine + oxycodone hydrochloride group (DQ group) by a random number table method, with 30 cases in each group. At the time before anesthesia induction (T0), and immediately (T1), 1 min (T2), 10 min (T3) and 30 minutes (T4) after extubation, the general vital signs of three groups were observed, and plasma cortisol (COR), epinephrine (E), norepinephrine (NE) and blood glucose (GLU) were measured. The spontaneous respiration recovery time, wake-up time, VAS score of each time period after extubation, extubation quality score, and adverse event rate were recorded. RESULTS: The vital signs at each time point of extubation, recovery time of spontaneous respiration, wake-up time, and extubation quality of DQ group were better than those of DEX group and Q group (P<0.05). The incidence of agitation, VAS score at T2 and T3, plasma concentrations of Cor, E, NE and Glu at T1, T3 and T4 in DQ group were significantly lower than those in Q group and DEX group (P<0.05). CONCLUSION: Oxycodone hydrochloride combined with dexmedetomidine can improve the recovery quality and reduce stress response in patients with LC after anesthesia, and can be safely used in patients with LC.

Excessive hydrogen sulfide-induced activation of NMDA receptors in the colon participates in anxiety- and compulsive-like behaviors in a rodent model of hemorrhagic shock and resuscitation.

OBJECTIVE: Hemorrhagic shock and resuscitation (HSR) cause inflammatory responses in the gastrointestinal tract and is associated with substantial morbidity and mortality rates. Hydrogen sulfide (H2S), a gasotransmitter with pleiotropic activity, exhibits anti-inflammatory benefits at physiological levels. However, deleterious effects are observed when its concentration increases. In this investigation, we employed a mouse model of HSR to examine the effects of an H2S scavenger on the gastrointestinal tract and brain, with emphasis on N-Methyl-d-Aspartate (NMDA) receptor function. METHODS: Mice were immediately administered dl-propargylglycine (PAG) intragastrically as an H2S scavenger after HSR exposure. The O-maze and buried beads tests were used to assess compulsive- and anxiety-like behaviors. Pathological changes in the intestine were evaluated at 24 and 30 days after HSR. Subsequently, at 30 days after HSR, we examined electrophysiological and pathological changes in the amygdala. RESULTS: Within 24 h of HSR exposure, animals treated with PAG showed significantly lower colonic injury. Additionally, compared to the HSR-treated mice 30 days after HSR, the PAG-treated mice displayed reduced buried beads, increased open-arm time, lower blood levels of Diamine Oxidase (DAO) and considerably improved ZO-1 intensity, a stronger association between the delta rhythm phase and beta activity amplitude, and lower neuroinflammatory response in the amygdala. MK-801, an NMDA receptor inhibitor, significantly reversed H2S-induced intestinal and cerebral injury. CONCLUSION: This experimental data suggests that H2S-induced excessive activation of NMDA receptors contributes to anxiety- and compulsive-like behaviors caused by HSR.