Preoperative acute hypervolemic hemodilution (AHHD) is a technique used in anesthesia to reduce the number of blood cells lost during intraoperative bleeding. The aim of the present study was to evaluate the effect of the hypervolemic hemodilution of 6% hydroxyethyl starch 130/0.4 on the EC50 of propofol at two clinical endpoints. A total of 20 patients undergoing AHHD following epidural anesthesia were studied, and 20 patients who did not receive hemodilution were used as a control group. All patients were American Society of Anesthesiologists grade I, aged 20–40 years and undergoing hip arthroplasty surgery. In the AHHD group, 10 ml/kg lactated Ringer's solution was infused over 20 min at the same time as the epidural test dose. The infusion was followed by the infusion of 6% hydroxyethyl starch 130/0.4 over 30 min. Patients in the control group received 10 ml/kg Ringer's solution over 50 min. Propofol was then delivered by a Diprifusor target-controlled infusion. The predicted blood and effect-site propofol concentrations were recorded at loss of consciousness (LOC) and return of consciousness (ROC). Probit analysis was used to estimate the values for predicted blood and effect-site concentrations at the two clinical endpoints. The results showed that the potency of propofol was decreased during AHHD. Compared with the controls, the predicted blood and effect-site concentrations of propofol at LOC were higher in patients of the hemodilution group, resulting in higher EC50 values (P=0.001 and 0.025, respectively). At ROC, the effect-site EC50 was 2.9 µg/ml [95% confidence interval (CI), 2.8–3.0] in hemodilution patients and 2.5 µg/ml (95% CI, 2.2–2.6) in control patients (P=0.001). With AHHD, the LOC time was significantly longer and the propofol dose was higher, while ROC times were comparable. In conclusion, AHHD increases the requirement for propofol at LOC and prolongs LOC time. Patients with AHHD recovered consciousness at higher effect-site concentrations of propofol. Thus, the induction dose of propofol should be increased during AHHD.

Objectives: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calci c aortic valve disease (CAVD).Background: The morbidity and mortality rates of calci c aortic valve disease (CAVD) remain high while treatment options are limited.Methods: In vivo , we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice assessment of aortic valve calci cation lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). We used siRNA to knock down Herpud1 in cultured Primary AVICs were isolated from mice to further validate our ndings.Results: Herpud1 was highly expressed in calci ed human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Herpud1 de ciency inhibited hcy-induced CAVD in vitro and in vivo.Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. ERS inhibitor 4-phenyl butyric acid (4-PBA) signi cantly attenuated aortic valve calci cation in high methionine diet-fed low-density lipoprotein receptor -/-(LDLR -/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis.Conclusions: These ndings identify a previously unknown mechanism of Herpud1 upregulation in CAVD progression, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression. HighlightsHomocysteine (hcy) promotes aortic valvular calci cation in vivo and in vitro.Herpud1 is upregulated in the lea ets of mice and humans with CAVD. Herpud1 de ciency inhibited hcy-induced CAVD in vitro and in vivo.Herpud1 silencing activates cell autophagy, inhibiting osteogenic differentiation of primary aortic valve interstitial cells (AVICs) induced by hcy. 4-Phenyl butyric acid, a compound that suppresses ERS and subsequent Herpud1 biosynthesis, signi cantly decreased AVIC calci cation in vitro after hcy stimulation and mitigated the severity of aortic valve brosis and calci cation in a murine model of CAVD.

Objectives: To evaluate the role and therapeutic value of homocysteine (hcy)-inducible endoplasmic reticulum stress (ERS) protein with ubiquitin like domain 1 (Herpud1) in hcy-induced calcific aortic valve disease (CAVD). Background: The morbidity and mortality rates of calcific aortic valve disease (CAVD) remain high while treatment options are limited.Methods: In vivo , we use the low-density lipoprotein receptor (LDLR) and Herpud1 double knockout (LDLR-/-/Herpud1-/-) mice assessment of aortic valve calcification lesions, ERS activation, autophagy, and osteogenic differentiation of aortic valve interstitial cells (AVICs). We used siRNA to knock down Herpud1 in cultured Primary AVICs were isolated from mice to further validate our findings. Results: Herpud1 was highly expressed in calcified human and mouse aortic valves as well as primary aortic valve interstitial cells (AVICs). Herpud1 deficiency inhibited hcy-induced CAVD in vitro and in vivo. Herpud1 silencing activated cell autophagy, which subsequently inhibited hcy-induced osteogenic differentiation of AVICs. Hcy increased Herpud1 expression through the ERS pathway and promoted CAVD progression. ERS inhibitor 4-phenyl butyric acid (4-PBA) significantly attenuated aortic valve calcification in high methionine diet–fed low-density lipoprotein receptor-/- (LDLR-/-) mice by suppressing ERS and subsequent Herpud1 biosynthesis. Conclusions: These findings identify a previously unknown mechanism of Herpud1 upregulation in CAVD progression, suggesting that Herpud1 silencing or inhibition is a viable therapeutic strategy for arresting CAVD progression.