Purpose
Remimazolam, an ultra-short-acting benzodiazepine sedative is equally effective as propofol in induction and maintenance of general anesthesia with improved hemodynamic stability in American ...Society of Anesthesiologists (ASA) Class I and II patients. This trial investigated remimazolam’s efficacy and safety in vulnerable patients (ASA Class III) undergoing elective general surgery.
Methods
A multicenter, randomized, double-blind, parallel-group trial in 67 adult surgical patients undergoing general anesthesia with two remimazolam induction doses (6 mg kg
−1
h
−1
—group A and 12 mg kg
−1
h
−1
—group B) has been conducted in 6 trials sites in Japan. Remimazolam was infused up to 2 mg kg
−1
h
−1
for maintenance of anesthesia in both groups.
Results
The functional anesthetic capability of the investigated drug was 100% in both arms. The mean time to loss of consciousness (LoC) was significantly shorter in group B (81.7 s) compared to group A (97.2 s),
p
= 0.0139. The mean bispectral index (BIS) value during maintenance of anesthesia ranged from 46.0 to 68.0 and from 44.7 to 67.5 in group A and B, respectively. There was no statistically significant difference between the remimazolam arms concerning the incidence of blood pressure (BP) decrease (67.7% in group B vs. 54.8% in group A), recovery profile or the incidence or severity of adverse events (AEs) or adverse drug reactions (ADRs).
Conclusion
Both induction regimens (6 and 12 mg kg
−1
h
−1
) were equally efficacious and safe in surgical patients ASA Class III. A significantly shorter time to LoC was observed with the higher remimazolam dosage.
Clinical trial registration
This trial is registered with the Japan Pharmaceutical Information Center—Clinical Trials Information (JapicCTI). JapicCTI number: 121977.
Purpose
The effects of remimazolam on autonomic nervous activity have not been elucidated. We investigated the differential effects of remimazolam and propofol on autonomic nervous activity during ...anesthesia induction.
Methods
Thirty patients were randomly divided into a remimazolam group or a propofol group for anesthesia induction. Hemodynamics and indices of heart rate variability were recorded before and after anesthesia. Low frequency power (LF; 0.04–0.15 Hz, ms
2
) and high frequency power (HF; 0.15–0.4 Hz, ms
2
) were calculated from power spectral density of heart rate variability. LF reflects both sympathetic and parasympathetic activities and HF reflects parasympathetic activity. To investigate the balance between sympathetic and parasympathetic activities, the normalized unit (%) of LF (LF nu) and that of HF (HF nu) were calculated. Changes in LF nu (ΔLF nu) before and after anesthesia (ΔLF nu = LF nu at awake—LF nu after anesthesia) were compared between the groups.
Results
Remimazolam and propofol decreased blood pressure and power spectral density of heart rate variability. Remimazolam did not change LF nu and HF nu, while propofol increased LF nu and decreased HF nu (
P
= 0.020). ΔLF nu in the remimazolam group (1.4 ± 23.6%) were less than that in the propofol group (19.3 ± 22.4%,
P
= 0.0415).
Conclusion
Remimazolam and propofol decreased autonomic nervous activity during anesthesia induction. Remimazolam preserved the balance of sympathetic and parasympathetic activities, while propofol modulated it to sympathetic dominance.
The Hayabusa2 spacecraft collected samples from the surface of the carbonaceous near-Earth asteroid (162173) Ryugu, and brought them to Earth. The samples were expected to contain organic molecules, ...which record processes that occurred in the early Solar System. We analyzed organic molecules extracted from the Ryugu surface samples. We identify a variety of molecules containing the atoms CHNOS, formed by methylation, hydration, hydroxylation, and sulfurization reactions. Amino acids, aliphatic amines, carboxylic acids, polycyclic aromatic hydrocarbons, and nitrogen-heterocyclic compounds were detected, with properties consistent with an abiotic origin. These compounds likely arose from aqueous reaction on Ryugu’s parent body and are similar to organics in Ivuna-type meteorites. These molecules can survive on the surfaces of asteroids and be transported throughout the Solar System.
Carbonaceous (C-type) asteroids
are relics of the early Solar System that have preserved primitive materials since their formation approximately 4.6 billion years ago. They are probably analogues of ...carbonaceous chondrites
and are essential for understanding planetary formation processes. However, their physical properties remain poorly known because carbonaceous chondrite meteoroids tend not to survive entry to Earth's atmosphere. Here we report on global one-rotation thermographic images of the C-type asteroid 162173 Ryugu, taken by the thermal infrared imager (TIR)
onboard the spacecraft Hayabusa2
, indicating that the asteroid's boulders and their surroundings have similar temperatures, with a derived thermal inertia of about 300 J m
s
K
(300 tiu). Contrary to predictions that the surface consists of regolith and dense boulders, this low thermal inertia suggests that the boulders are more porous than typical carbonaceous chondrites
and that their surroundings are covered with porous fragments more than 10 centimetres in diameter. Close-up thermal images confirm the presence of such porous fragments and the flat diurnal temperature profiles suggest a strong surface roughness effect
. We also observed in the close-up thermal images boulders that are colder during the day, with thermal inertia exceeding 600 tiu, corresponding to dense boulders similar to typical carbonaceous chondrites
. These results constrain the formation history of Ryugu: the asteroid must be a rubble pile formed from impact fragments of a parent body with microporosity
of approximately 30 to 50 per cent that experienced a low degree of consolidation. The dense boulders might have originated from the consolidated innermost region or they may have an exogenic origin. This high-porosity asteroid may link cosmic fluffy dust to dense celestial bodies
.
Samples of the carbonaceous asteroid (162173) Ryugu were collected and brought to Earth by the Hayabusa2 spacecraft. We investigated the macromolecular organic matter in Ryugu samples and found that ...it contains aromatic and aliphatic carbon, ketone, and carboxyl functional groups. The spectroscopic features of the organic matter are consistent with those in chemically primitive carbonaceous chondrite meteorites that experienced parent-body aqueous alteration (reactions with liquid water). The morphology of the organic carbon includes nanoglobules and diffuse carbon associated with phyllosilicate and carbonate minerals. Deuterium and/or nitrogen-15 enrichments indicate that the organic matter formed in a cold molecular cloud or the presolar nebula. The diversity of the organic matter indicates variable levels of aqueous alteration on Ryugu's parent body.
Remote ischemic preconditioning (RIPC) offers cardioprotection against myocardial ischemia–reperfusion injury. The humoral factors involved in RIPC that are released from parasympathetically ...innervated organs have not been identified. Previous studies showed that ghrelin, a hormone released from the stomach, is associated with cardioprotection. However, it is unknown whether or not ghrelin is involved in the mechanism of RIPC. This study aimed to determine whether ghrelin serves as one of the humoral factors in RIPC. RIPC group rats were subjected to three cycles of ischemia and reperfusion for 5 min in two limbs before left anterior descending (LAD) coronary artery ligation. Unacylated ghrelin (UAG) group rats were given 0.5 mcg/kg UAG intravenously 30 min before LAD ligation. Plasma levels of UAG in all groups were measured before and after RIPC procedures and UAG administration. Additionally, JAK2/STAT3 pathway inhibitor (AG490) was injected in RIPC and UAG groups to investigate abolishment of the cardioprotection of RIPC and UAG. Plasma levels of UAG, infarct size and phosphorylation of STAT3 were compared in all groups. Infarct size was significantly reduced in RIPC and UAG groups, compared to the other groups. Plasma levels of UAG in RIPC and UAG groups were significantly increased after RIPC and UAG administration, respectively. The cardioprotective effects of RIPC and UAG were accompanied by an increase in phosphorylation of STAT3 and abolished by AG490. This study indicated that RIPC reduces myocardial ischemia and reperfusion injury through UAG-induced activation of JAK/STAT pathway. UAG may be one of the humoral factors involved in the cardioprotective effects of RIPC.
BACKGROUND:Dexmedetomidine (DEX) has a direct cardioprotective effect against ischemia/reperfusion injury through endothelial nitric oxide synthase (eNOS) phosphorylation via α2-adrenoreceptor ...(α2-AR). By using spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat models, the cardioprotective effect of DEX in hypertrophied myocardium and the differential characteristics of cardiac α2-AR and the I1 imidazoline receptor (I1R) were examined.
METHODS:Langendorff-perfused rat hearts underwent 40 minutes of global ischemia followed by 120 minutes of reperfusion in the presence or absence of DEX before ischemia. Infarct size was measured, and eNOS phosphorylation was assessed by Western blotting. The presence and expression of the receptors were assessed by immunohistochemistry, real-time reverse transcriptase polymerase chain reaction, and Western blotting.
RESULTS:In WKY, DEX significantly decreased infarct size and increased phosphorylated-eNOS/eNOS. These effects were counteracted by yohimbine (α2-AR antagonist) and efaroxan (α2-AR and I1R antagonist). In SHR, DEX significantly decreased infarct size, and the effect was counteracted by efaroxan but not yohimbine. DEX did not alter phosphorylated-eNOS/eNOS in SHR. α2-AR and I1R were observed in WKY and SHR hearts. Although alpha2A-AR and alpha2B-AR messenger RNA and protein levels were upregulated in SHR, I1R expression was comparable between the 2 species.
CONCLUSIONS:In the hypertrophied heart, DEX maintains its direct cardioprotective effect against ischemia/reperfusion injury via I1R in an eNOS-nondependent manner despite upregulation of α2-AR.
Myocardial ischemia-reperfusion (I/R) injury induces endothelial glycocalyx (GCX) degradation. Several candidate GCX-protective factors including albumin have been identified, few have been ...demonstrated in in vivo studies and most albumins used to date have been heterologous. Albumin is a carrier protein for sphingosine 1-phosphate (S1P), which has protective effects on the cardiovascular system. However, changes inhibited by albumin in the endothelial GCX structure in I/R in vivo via the S1P receptor has not been reported. In this study, we aimed to determine whether albumin prevents the shedding of endothelial GCX in response to I/R in vivo. Rats were divided into four groups: control (CON), I/R, I/R with albumin preload (I/R + ALB), and I/R + ALB with S1P receptor agonist fingolimod (I/R + ALB + FIN). FIN acts as an initial agonist of S1P receptor 1 and downregulates the receptor in an inhibitory manner. The CON and I/R groups received saline and I/R + ALB and I/R + ALB + FIN groups received albumin solution before left anterior descending coronary artery ligation. Our study used rat albumin. Shedding of endothelial GCX was evaluated in the myocardium by electron microscopy, and the concentration of serum syndecan-1 was measured. Thus, albumin administration maintained the structure of endothelial GCX and prevented shedding of endothelial GCX via the S1P receptor in myocardial I/R, and FIN annihilated the protective effect of albumin against I/R injury.
•Albumin have been identified as a candidate protective factor for endothelial glycocalyx, few have been demonstrated in in vivo studies and most albumins used to date have been heterologous.•Albumin is a carrier protein for sphingosine 1-phosphate, which has protective effects on the cardiovascular system.•The protection effect by albumin in the glycocalyx in ischemia/reperfusion injury in vivo via the S1P receptor has not been reported.•In this study, we aimed to determine whether homologous albumin prevents the shedding of endothelial GCX in response to ischemia/reperfusion in vivo.•Albumin prevented shedding of endothelial GCX via the S1P receptor in myocardial ischemia/reperfusion.
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