Rationale Nitric oxide, the classic endothelial derived relaxing factor (EDRF), acts via cyclic GMP and calcium without notably affecting membrane potential. A major component of EDRF activity derives from hyperpolarization and is termed endothelial derived hyperpolarizing factor (EDHF). Hydrogen sulfide (H2S) is a prominent EDRF, since mice lacking its biosynthetic enzyme, cystathionine γ-lyase (CSE), display pronounced hypertension with deficient vasorelaxant responses to acetylcholine. Objective The purpose of this study is to determine if H2S is a major physiologic EDHF. Methods and Results We now show that H2S is a major EDHF, as in blood vessels of CSE deleted mice hyperpolarization is virtually abolished. H2S acts by covalently modifying (sulfhydrating) the ATP-sensitive potassium channel, as mutating the site of sulfhydration prevents H2S-elicited hyperpolarization. The endothelial intermediate conductance (IKCa) and small conductance (SKCa) potassium channels mediate in part the effects of H2S, as selective IKCa and SKCa channel inhibitors, charybdotoxin and apamin, inhibit glibenclamide insensitive H2S induced vasorelaxation. Conclusions H2S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. As EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H2S biosynthesis offer therapeutic potential.

Video distraction, parental presence, or their combination showed similar effects on preoperative anxiety during inhaled induction of anesthesia and postoperative behavioral outcomes in preschool children having surgery.

Nitric oxide (NO) can modulate arterial stiffness by regulating both functional and structural changes in the arterial wall. Tissue transglutaminase (TG2) has been shown to contribute to increased central aortic stiffness by catalyzing the cross-linking of matrix proteins. NO S-nitrosylates and constrains TG2 to the cytosolic compartment and thereby holds its cross-linking function latent. In the present study, the role of endothelial NO synthase (eNOS)-derived NO in regulating TG2 function was studied using eNOS knockout mice. Matrix-associated TG2 and TG2 cross-linking function were higher, whereas TG2 S-nitrosylation was lower in the eNOS(-/-) compared with wild-type (WT) mice. Pulse-wave velocity (PWV) and blood pressure measured noninvasively were elevated in the eNOS(-/-) compared with WT mice. Intact aortas and decellularized aortic tissue scaffolds of eNOS(-/-) mice were significantly stiffer, as determined by tensile testing. The carotid arteries of the eNOS(-/-) mice were also stiffer, as determined by pressure-dimension analysis. Invasive methods to determine the PWV-mean arterial pressure relationship showed that PWV in eNOS(-/-) and WT diverge at higher mean arterial pressure. Thus eNOS-derived NO regulates TG2 localization and function and contributes to vascular stiffness.

Cardiovascular dysfunction is a primary independent predictor of age-related morbidity and mortality. Frailty is associated with activation of inflammatory pathways and fatigue that commonly presents and progresses with age. Interleukin 10 (IL-10), the cytokine synthesis inhibitory factor, is an anti-inflammatory cytokine produced by immune and non-immune cells. Homozygous deletion of IL-10 in mice yields a phenotype that is consistent with human frailty, including age-related increases in serum inflammatory mediators, muscular weakness, higher levels of IGF-1 at midlife, and early mortality. While emerging evidence suggests a role for IL-10 in vascular protection, a clear mechanism has not yet been elucidated. Methods In order to evaluate the role of IL-10 in maintenance of vascular function, force tension myography was utilized to access ex-vivo endothelium dependent vasorelaxation in vessels isolated from IL-10 knockout IL-10(tm/tm) and control mice. Pulse wave velocity ((PWV), index of stiffness) of vasculature was measured using ultrasound and blood pressure was measured using the tail cuff method. Echocardiography was used to elucidated structure and functional changes in the heart. Results Mean arterial pressures were significantly higher in IL-10(tm/tm) mice as compared to C57BL6/wild type (WT) controls. PWV was increased in IL-10(tm/tm) indicating stiffer vasculature. Endothelial intact aortic rings isolated from IL-10(tm/tm) mice demonstrated impaired vasodilation at low acetylcholine doses and vasoconstriction at higher doses whereas vasorelaxation responses were preserved in rings from WT mice. Cyclo-oxygenase (COX-2)/thromboxane A2 inhibitors improved endothelial dependent vasorelaxation and reversed vasoconstriction. Left ventricular end systolic diameter, left ventricular mass, isovolumic relaxation time, fractional shortening and ejection fraction were all significantly different in the aged IL-10(tm/tm) mice compared to WT mice. Conclusion Aged IL-10(tm/tm) mice have stiffer vessels and decreased vascular relaxation due to an increase in eicosanoids, specifically COX-2 activity and resultant thromboxane A2 receptor activation. Our results also suggest that aging IL-10(tm/tm) mice have an increased heart size and impaired cardiac function compared to age-matched WT mice. While further studies will be necessary to determine if this age-related phenotype develops as a result of inflammatory pathway activation or lack of IL-10, it is essential for maintaining the vascular compliance and endothelial function during the aging process. Given that a similar cardiovascular phenotype is present in frail, older adults, these findings further support the utility of the IL-10(tm/tm) mouse as a model of frailty.

The displacement of beating heart for positioning during anastomosis of the graft to OM artery caused significant derangement of RV function and decrease in CO. A thermodilution catheter continuously measuring the CO and RVEF was useful to monitor the change in RV function and volume during OPCAB.

BackgroundA prospective, double blind study was performed to compare the clinical effect of vertical infraclavicular and supraclavicular brachial plexus block using a nerve stimulator for upper limb surgery.MethodsOne hundred patients receiving upper limb surgery under infraclavicular or supraclavicular brachial plexus block were enrolled in this study. The infraclavicular brachial plexus block was performed using the vertical technique with 30 ml of 0.5% ropivacaine. The supraclavicular brachial plexus block was performed using the plumb bob technique with 30 ml of 0.5% ropivacaine. The block performance-related pain was evaluated. This study observed which nerve type was stimulated, and scored the sensory and motor block. The quality of the block was assessed intra-operatively. The duration of the sensory and motor block as well as the complications were assessed. The patient's satisfaction with the anesthetic technique was assessed after surgery.ResultsThere were no significant differences in the block performance-related pain, frequency of the stimulated nerve type, evolution of sensory and motor block quality, or the success of the block. There were no significant differences in the duration of the sensory and motor block. There was a significant difference in the incidence of Horner's syndrome. Two patients had a pneumothorax in the supraclavicular approach. There were no significant differences in the patient's satisfaction.ConclusionsBoth infraclavicular and supraclavicular brachial plexus block had similar effects. The infraclavicular approach may be preferred to the supraclavicular approach when considering the complications.

BackgroundThis prospective, randomized controlled study was undertaken to compare stress hormone response to open thoracotomy for lung resection at different anesthetic depths, as determined by bispectral index (BIS) monitoring, in patients under propofol-remifentanil anesthesia.MethodsForty-eight adult patients scheduled for lung resection surgery using one-lung ventilation were randomly assigned to either a deep anesthesia group (BIS score of 40 ± 5, n = 24) or a light anesthesia group (BIS score of 60 ± 5, n = 24) by adjusting propofol infusion rates. Blood norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol levels were measured before the induction of anesthesia, at the end of surgery, and at 2 hours postoperatively. Blood glucose, hemodynamic, and oxygenation-ventilation variables, and postoperative outcomes were also measured.ResultsNorepinephrine and epinephrine levels remained unchanged over time in the deep group, but norepinephrine levels significantly increased in the light group at 2 h after surgery than at baseline (P = 0.007 and 0.004, respectively). Temporal changes in norepinephrine, but not in epinephrine, were significantly different between the two groups (P = 0.036). Plasma glucose levels in the light group increased with time and were significantly higher than in the deep group at the end of surgery (P = 0.002).ConclusionsA deep level of anesthesia achieved using high propofol infusion rates during lung surgery provided lower perioperative norepinephrine and glucose responses than light level of anesthesia during the early postoperative period but failed to affect immediate postoperative outcomes.

BackgroundWe evaluated the effect of two drugs with anti-inflammatory action, dexamethasone and ketorolac, on reduction of postoperative sore throat (POST) after general anesthesia with endotracheal intubation in patients undergoing thyroidectomy.MethodsOne hundred and ninety-two female patients scheduled to undergo general anesthesia with endotracheal intubation for thyroidectomy were enrolled in this prospective study. Participants were randomly allocated to receive intravenous medication; placebo (Group C, n = 45), ketorolac 30 mg immediately before intubation (Group Kpre, n = 47), ketorolac 30 mg at the end of surgery (Group Kpost, n = 45) and dexamethasone 10 mg (Group D, n = 43). The incidence and severity of POST and hoarseness were evaluated at 1, 6 and 24 hours after surgery.ResultsIncidences and severities of POST at rest and during swallowing in first 6 hours after extubation were comparable among 4 groups. At 24 hours postextubation, the incidence (P = 0.002, 95% CI of proportion differences; 0.05–0.39) and severity (P = 0.008) of POST during swallowing were significantly lower in group D than in group C. Kpre and Kpost groups did not show a greater reduction in POST than group C, despite lower rescue analgesic requirement at 1 hour after extubation in group Kpre (P = 0.006; 95% CI of proportion differences; 0.07–0.38). No intergroup differences were observed in incidences of hoarseness or adverse events.ConclusionsIntravenous administration of dexamethasone 10 mg, but not ketorolac, before induction of anesthesia reduces the incidence and severity of POST during swallowing at 24 hours after thyroidectomy.