Propofol But Not Desflurane Maintains Rat Cerebral Arteriolar Responses to Acetylcholine During Acute Hyperglycemia.

BACKGROUND: Acute hyperglycemia causes vascular endothelial dysfunction in various organs including the cerebral vessels. It is associated with increased mortality and morbidity in the perioperative period. The impact of anesthetic agents on cerebral vasodilatory responses during hyperglycemia remains unclear. We investigated endothelial function in rat cerebral arterioles during acute hyperglycemia, under propofol or desflurane anesthesia. MATERIALS AND METHODS: A closed cranial window preparation was used to measure changes in pial arteriole diameter induced by topical application of acetylcholine (ACh), an endothelium-dependent vasodilator, in rats anesthetized with propofol or desflurane. Pial arteriole responses to ACh were measured during normoglycemia and hyperglycemia. We then investigated whether the response of cerebral arterioles to acute hyperglycemia under propofol anesthesia were related to propofol or its vehicle, intralipid. RESULTS: ACh resulted in a dose-dependent dilation of cerebral arterioles during propofol and desflurane anesthesia under normoglycemic conditions. The vasodilatory effects of ACh were also maintained under hyperglycemic conditions during propofol anesthesia, but the vasodilator response to ACh was significantly impaired during hyperglycemia compared with normoglycemia with desflurane anesthesia. The vasodilatory effects of ACh were maintained during normoglycemia and hyperglycemia in rats receiving propofol or intralipid. CONCLUSIONS: Rat pial arteriole responses to ACh are maintained during conditions of acute hyperglycemia with propofol anesthesia but suppressed compared with normoglycemia with desflurane anesthesia.

A Comparison of the Required Bronchial Cuff Volume Obtained by 2 Cuff Inflation Methods, Capnogram Waveform-Guided Versus Pressure-Guided: A Prospective Randomized Controlled Study.

BACKGROUND: Double-lumen endobronchial tubes (DLTs) are used for one-lung ventilation (OLV) during thoracic surgery. Overinflation into the bronchial cuff causes damage to the tracheobronchial mucosa, whereas underinflation leads to an incomplete collapse of the nonventilated lung or incomplete ventilation of the ventilated lung. However, how to determine the appropriate bronchial cuff volume and pressure during OLV is unclear. The objective of this study is to compare the required bronchial cuff volume for lung separation obtained by 2 different cuff inflation methods under closed- and open-chest conditions. METHODS: A total of 64 patients scheduled to undergo elective thoracic surgery requiring OLV were recruited. Left DLTs were used for both right- and left-sided surgery. The patients were randomly assigned to 1 of 2 inflation-type groups to estimate the bronchial cuff volume. In the capnogram waveform-guided bronchial cuff inflation group (capno group, n = 27), the bronchial cuff was inflated until a capnometer sampling gas containing CO2 from the nonventilated lung displayed a flat line. The corresponding bronchial cuff volume and pressure were then recorded. In the pressure-guided bronchial cuff inflation group (pressure group, n = 29), the bronchial cuff was inflated by a cuff inflator to a pressure of 20 cm H2O. Lung separation was confirmed when a flat line of a capnometer was observed after gas sampling from the nonventilated lung. RESULTS: Under closed-chest conditions, the bronchial cuff sealing volume for the capno group was significantly lower than that for the pressure group (mean [standard deviation {SD}], 1.00 [0.65] mL vs 1.44 [0.59] mL, mean difference, -0.44; 97.5% confidence interval [CI], -0.78 to -0.11; P = .010). Under open-chest conditions, the bronchial cuff sealing volume for the capno group was also significantly lower than that for the pressure group (mean [SD], 0.65 [0.66] mL vs 1.22 [0.45] mL, mean difference, -0.58; 97.5% CI, -0.88 to -0.27; P < .001). CONCLUSIONS: The lowest cuff volume providing an air-tight bronchial seal was obtained by the capnogram waveform-guided bronchial cuff inflation method. Since the cuff volume required to achieve an air-tight seal decreases after opening the chest, readjustment of the bronchial cuff volume to prevent bronchial cuff damage to the tracheobronchial mucosa after opening the chest may be advisable.

Cigarette Smoking Cessation Temporarily Enhances the Release of Phosphorylated-HSP27 from Human Platelets.

Objective Cigarette smoking is a risk factor for arteriopathy, including acute coronary syndrome, stroke and peripheral vascular disease. Thus, cessation is strongly recommended in order to reduce these risks. We recently demonstrated that smoking cessation causes temporary hyper-aggregability of human platelets. We previously showed that heat shock protein 27 (HSP27) is released from human platelets stimulated by collagen, accompanied by its phosphorylation. Accumulating evidence indicates potent roles of extracellular HSP27 as a modulator of inflammation. In the present study, using the stored samples obtained in the previous study, we investigated the effect of cigarette smoking cessation on the release of phosphorylated-HSP27 from collagen-activated human platelets (n=15 patients). Methods We enrolled patients who visited smoking cessation outpatient services between January 2012 and November 2014. Platelet-rich plasma, chronologically obtained before and after the cessation, was stimulated by collagen using a PA-200 aggregometer in the previous study. The levels of phosphorylated-HSP27 released from platelets were determined by an enzyme-linked immunosorbent assay. The phosphorylation of HSP27 in platelets was evaluated by a Western blot analysis. Results Cessation of cigarette smoking significantly upregulated the levels of collagen-stimulated release of phosphorylated-HSP27 at four and eight weeks after quitting smoking compared to before cessation. However, there was no significant difference between the levels before cessation and those at 12 weeks after cessation. The levels of phosphorylated-HSP27 stimulated by collagen in the platelets at four weeks after smoking cessation were remarkably enhanced compared to before cessation. Conclusion Cigarette smoking cessation temporarily enhances the collagen-stimulated release of phosphorylated-HSP27 from human platelets in the short term.

Smoking cessation affects human platelet activation induced by collagen.

It is firmly established that smoking is a risk factor of cardiovascular disease, stroke and peripheral vascular disease. Although smoking alters the hemostatic process, the influence of smoking on human platelet activation remains controversial. For patients undergoing surgery, cessation of smoking prior to the procedure is recommended as it increases the risk of postoperative morbidity or mortality. The presented study investigated the effects of smoking cessation on human platelet activation induced via collagen (n=19 patients). Blood samples were taken on four occasions: Before smoking cessation, and at 4, 8 and 12 weeks after smoking cessation. Platelet aggregation using citrated platelet-rich plasma (PRP) was monitored using a PA-200 aggregometer, which determined the size of platelet aggregates using laser scattering methods. A low dose of collagen (1 µg/ml) accelerated platelet aggregation at 4 or 8 weeks after smoking cessation when compared with results before cessation. After 12 weeks, levels of platelet aggregation induced by collagen were almost equal to those recorded prior to smoking cessation. The secretion levels of collagen-induced platelet-derived growth factor (PDGF)-AB at 4 or 8 weeks after smoking cessation were significantly higher than those before smoking was stopped. Furthermore, smoking cessation markedly strengthened the collagen-induced phosphorylation of p38 mitogen-activated protein (MAP) kinase after 4 weeks. The results of the current study indicated that smoking cessation causes temporary short-term human platelet hyper-activation. The further suggest that the incidence of complications due to human platelet hyper-reactivity may be lowered by considering the period of smoking abstinence.

Cerebrovascular reactivity to hypercapnia during sevoflurane or desflurane anesthesia in rats.

BACKGROUND: Hypercapnia causes dilation of cerebral vessels and increases cerebral blood flow, resulting in increased intracranial pressure. Sevoflurane is reported to preserve cerebrovascular carbon dioxide reactivity. However, the contribution of inhaled anesthetics to vasodilatory responses to hypercapnia has not been clarified. Moreover, the cerebrovascular response to desflurane under hypercapnia has not been reported. We examined the effects of sevoflurane and desflurane on vasodilatory responses to hypercapnia in rats. METHODS: A closed cranial window preparation was used to measure the changes in pial vessel diameters. To evaluate the cerebrovascular response to hypercapnia and/or inhaled anesthetics, the pial vessel diameters were measured in the following states: without inhaled anesthetics at normocapnia (control values) and hypercapnia, with inhaled end-tidal minimal alveolar concentration (MAC) of 0.5 or 1.0 of either sevoflurane or desflurane at normocapnia, and an MAC of 1.0 of sevoflurane or desflurane at hypercapnia. RESULTS: Under normocapnia, 1.0 MAC, but not 0.5 MAC, of sevoflurane or desflurane dilated the pial arterioles and venules. In addition, under both 1.0 MAC of sevoflurane and 1.0 MAC of desflurane, hypercapnia significantly dilated the pial arterioles and venules in comparison to their diameters without inhaled anesthetics. The degrees of vasodilation were similar for desflurane and sevoflurane under both normocapnia and hypercapnia. CONCLUSIONS: Desflurane induces cerebrovascular responses similar to those of sevoflurane. Desflurane can be used as safely as sevoflurane in neurosurgical anesthesia.

Endothelium-dependent vasodilation in the cerebral arterioles of rats deteriorates during acute hyperglycemia and then is restored by reducing the glucose level.

PURPOSE: Acute hyperglycemia in patients with traumatic brain injury correlates with a poor neurological outcome. We investigated the endothelium function of rat cerebral arterioles during acute hyperglycemia and after reducing the glucose levels using insulin. We also examined whether or not oxidative stress was involved in the cerebral arteriole response to acute hyperglycemia. METHODS: In isoflurane-anesthetized, mechanically ventilated rats, we used closed cranial window preparation to measure the changes in the pial arteriolar diameter following the topical application of acetylcholine (ACh) or adenosine. We examined the pial arteriolar vasodilator response before hyperglycemia, during hyperglycemia, and after reducing the glucose level using insulin. After intravenous pretreatment with an NADPH oxidase inhibitor (apocynin or diphenylene iodonium), we reexamined the pial arteriolar vasodilator response following the topical application of ACh. RESULTS: Under control conditions, the topical application of ACh dose-dependently dilated the cerebral arterioles. The vasodilatory responses to topical ACh were impaired during hyperglycemia and improved after the administration of insulin. The vasodilatory responses to topical adenosine were not affected by the glucose levels. In the apocynin or diphenylene iodonium pretreatment group, the topical application of ACh dilated the cerebral arterioles during hyperglycemia. CONCLUSION: Acute hyperglycemia induces a dysfunction of the endothelium-dependent vasodilation of rat cerebral arterioles. The dysfunction can be reversed by improving the acute hyperglycemia and it can be prevented entirely by the administration of NADPH oxidase inhibitors. These results could suggest that controlling the glucose levels works protectivity to endothelium function of cerebral arterioles.

Effect of blood pressure elevation on cerebral oxygen desaturation in the beach chair position.

OBJECTIVE: The beach chair position (BCP) during shoulder arthroscopy is a known risk factor for cerebral ischemia. We retrospectively investigated whether maintaining the arterial blood pressure (ABP) prevented the decrease in the regional cerebral tissue oxygen saturation (rSO2). METHODS: We analyzed 20 consecutive patients who underwent elective shoulder surgery in the BCP under general anesthesia. The bilateral rSO2 was monitored continuously throughout the procedure with the help of near-infrared spectroscopy (INVOS 5100 Cerebral Oximeter, Somanetics Corporation, Troy, MI, USA). Anesthesiologists maintained patient blood pressure while they were in the BCP, which was measured using an ABP transducer placed at the level of the external auditory meatus. We compared rSO2 measured in the supine position and in the BCP. RESULTS: Measurement of cortex level mean ABP (mABP) values in the BCP were >50 mmHg and over 60% higher than those noted for the supine position in most patients. Although all bilateral rSO2 values in the BCP were significantly lower than those in the supine position, the reductions was <20%. Further, 35% (7 of 20) patients that were part of the study experienced cerebral desaturation events at any given point during the procedure. None of the patients experienced clinical postoperative neurological complications. CONCLUSIONS: Although cortex level mABP in the BCP was >50 mmHg, a decrease was recorded in the rSO2 values. This rSO2 decrease was proportional to the reduction in the cortex level mABP induced by a postural change to the BCP. Therefore, despite appropriate blood pressure management, shoulder surgery in the BCP might involve certain risks for patients with cerebrovascular diseases.

Sphingosine 1-phosphate (S1P) suppresses the collagen-induced activation of human platelets via S1P4 receptor.

Sphingosine 1-phosphate (S1P) is as an extracellular factor that acts as a potent lipid mediator by binding to specific receptors, S1P receptors (S1PRs). However, the precise role of S1P in human platelets that express S1PRs has not yet been fully clarified. We previously reported that heat shock protein 27 (HSP27) is released from human platelets accompanied by its phosphorylation stimulated by collagen. In the present study, we investigated the effect of S1P on the collagen-induced platelet activation. S1P pretreatment markedly attenuated the collagen-induced aggregation. Co-stimulation with S1P and collagen suppressed collagen-induced platelet activation, but the effect was weaker than that of S1P-pretreatment. The collagen-stimulated secretion of platelet-derived growth factor (PDGF)-AB and the soluble CD40 ligand (sCD40L) release were significantly reduced by S1P. In addition, S1P suppressed the collagen-induced release of HSP27 as well as the phosphorylation of HSP27. S1P significantly suppressed the collagen-induced phosphorylation of p38 mitogen-activated protein kinase. S1P increased the levels of GTP-bound Gαi and GTP-bound Gα13 coupled to S1PPR1 and/or S1PR4. CYM50260, a selective S1PR4 agonist, but not SEW2871, a selective S1PR1 agonist, suppressed the collagen-stimulated platelet aggregation, PDGF-AB secretion and sCD40L release. In addition, CYM50260 reduced the release of phosphorylated-HSP27 by collagen as well as the phosphorylation of HSP27. The selective S1PR4 antagonist CYM50358, which failed to affect collagen-induced HSP27 phosphorylation, reversed the S1P-induced attenuation of HSP27 phosphorylation by collagen. These results strongly suggest that S1P inhibits the collagen-induced human platelet activation through S1PR4 but not S1PR1.

Performance of a new carbon dioxide absorbent, Yabashi lime® as compared to conventional carbon dioxide absorbent during sevoflurane anesthesia in dogs.

In the present study, we compare a new carbon dioxide (CO2) absorbent, Yabashi lime(®) with a conventional CO2 absorbent, Sodasorb(®) as a control CO2 absorbent for Compound A (CA) and Carbon monoxide (CO) productions. Four dogs were anesthetized with sevoflurane. Each dog was anesthetized with four preparations, Yabashi lime(®) with high or low-flow rate of oxygen and control CO2 absorbent with high or low-flow rate. CA and CO concentrations in the anesthetic circuit, canister temperature and carbooxyhemoglobin (COHb) concentration in the blood were measured. Yabashi lime(®) did not produce CA. Control CO2 absorbent generated CA, and its concentration was significantly higher in low-flow rate than a high-flow rate. CO was generated only in low-flow rate groups, but there was no significance between Yabashi lime(®) groups and control CO2 absorbent groups. However, the CO concentration in the circuit could not be detected (≤5ppm), and no change was found in COHb level. Canister temperature was significantly higher in low-flow rate groups than high-flow rate groups. Furthermore, in low-flow rate groups, the lower layer of canister temperature in control CO2 absorbent group was significantly higher than Yabashi lime(®) group. CA and CO productions are thought to be related to the composition of CO2 absorbent, flow rate and canister temperature. Though CO concentration is equal, it might be safer to use Yabashi lime(®) with sevoflurane anesthesia in dogs than conventional CO2 absorbent at the point of CA production.

[Comparison of vecuronium doses in general anesthesia administered with remifentanil or fentanyl].

BACKGROUND: It is recommended to minimize neuromuscular blocker administration during general anesthesia for the efficacy of operating room utilization and potential hazards of unintended awareness during anesthesia. METHODS: We retrospectively compared the dose of vecuronium in consecutive 8,007 patients under general anesthesia receiving remifentanil or fentanyl. In analyzing electronic anesthesia records over 4 years in a single university institute, we also examined the type of general anesthesia and the required time of each pro- cedure in the operating room. RESULTS: Less vecuronium was necessary in patients administered remifentanil than those given fentanyl both maintained with inhalational and intravenous anesthesia. Supplementation with epidural anesthesia did not influence the dose of vecuronium in patients under general anesthesia receiving remifentanil or fentanyl. We also measured the time necessary before extubating trachea after finishing surgery, while no difference was found between the patients recieving remifentanil and fentanyl. CONCLUSIONS: Anesthesia with remifentanil reduces requirement of vecuronium dose greater than with fentanyl, while it does not affect the emergence time from anesthesia.

[Report of a tour of the surgical centers in the United States organized by the Japanese Association for Operative Medicine].

We, 4 authors, visited 4 surgical centers in the United States last year on a tour sponsored by the Japanese Association for Operative Medicine. The surgical center of each hospital we visited aimed to contribute to the hospital not only in terms of financial strength but also in the creation of a unique hospital brand value by increasing the number of surgeries compared with previous years as much as possible. The role of surgical centers in the United States was comparable with what we consider an ideal center in Japan. We also found that management of the surgical centers by directors who are specialized anesthesiologists is well organized to promote efficiency with respect to organization, utilities and human resources, and realized that these anesthesiologists must know how to manage the team members and the organization of the surgical centers to improve the quality of operative medicine.

The association between the initial end-tidal carbon dioxide difference and the lowest arterial oxygen tension value obtained during one-lung anesthesia with propofol or sevoflurane.

OBJECTIVE: The purpose of this study was to examine the correlation between the lowest PaO(2) value recorded during the first 45 minutes of one-lung ventilation (OLV) and the end-tidal CO(2) (ETCO(2)) difference between two-lung ventilation (TLV) and the early phase of OLV. DESIGN: A prospective, randomized study. SETTING: A university hospital. PARTICIPANTS: Thirty-six patients scheduled for elective thoracic surgery. INTERVENTIONS: Thoracic surgery patients were randomly assigned to 1 of 2 groups (group P [n = 18], maintained with propofol; group S [n = 18], maintained with sevoflurane). After setting up, the authors measured arterial blood gases at F(I)O(2) = 1.0 as follows: during TLV and at 5 minutes, 15 minutes, 30 minutes, and 45 minutes after the start of OLV. ETCO(2) was recorded just before and at 3 minutes after the start of OLV. The authors examined the relationship between the initial ETCO(2) difference and the lowest PaO(2) value recorded during the first 45 minutes of OLV. MEASUREMENTS AND MAIN RESULTS: There was a significant negative correlation between the lowest PaO(2) (x) value and the initial ETCO(2) difference (y) during OLV in each group (group P: y = -0.0203x + 7.2571, r(2) = 0.5351; group S: y = -0.0257x + 7.3158, r(2) = 0.6129). This correlation was not significantly different between the groups. CONCLUSION: The present study indicates that the ETCO(2) difference between TLV and early OLV has an association with impaired oxygenation later during OLV. This would be a simple and clinically convenient predictor of the lowest PaO(2) value likely to be reached during one-lung anesthesia with either propofol or sevoflurane.

Hypothermia attenuates the vasodilator effects of dexmedetomidine on pial vessels in rabbits in vivo.

UNLABELLED: Studies have indicated that mild to moderate hypothermia or dexmedetomidine may have neuroprotective properties in animal models. In this study, we investigated the effects of hypothermia on dexmedetomidine-induced responses in cerebral vessels in anesthetized rabbits by using the cranial-window preparation. After instrumentation under pentobarbital anesthesia, 12 rabbits were assigned to 1 of 2 equal groups: normothermic (nasopharyngeal and intrawindow temperature, 38.5 degrees C-39.5 degrees C) or hypothermic (33.0 degrees C-34.0 degrees C). Each rabbit received three different concentrations (10(-7), 10(-5), and 10(-3) M) of dexmedetomidine under the window, and cerebral pial vessel diameters were measured in a sequential manner. In the normothermic group, dexmedetomidine induced a significant concentration-dependent dilation in both large and small arterioles. In the hypothermia group, dexmedetomidine produced a U-shaped dose-response in both large and small cerebral arterioles (concentration-related vasoconstriction at 10(-7) and 10(-5) M, but vasodilation at 10(-3) M). In cerebral venules, a similar pattern of results was obtained, but changes were generally smaller than in arterioles. In conclusion, topically applied dexmedetomidine induces concentration-dependent dilation in cerebral arterioles in normothermic rabbits anesthetized with pentobarbital, but mild to moderate hypothermia attenuates these responses, with smaller dexmedetomidine concentrations causing vasoconstriction. IMPLICATIONS: In normothermic rabbits anesthetized with pentobarbital, topically applied dexmedetomidine induces a concentration-dependent dilation in both large and small cerebral arterioles, but mild to moderate hypothermia attenuates these responses.

Effects of ketamine on isoflurane- and sevoflurane-induced cerebral vasodilation in rabbits.

Although ketamine has been reported to have little effect on the cerebral circulation when used with other anesthetics, its effect on the cerebral vascular response to volatile anesthetics, which increase cerebral blood flow in a concentration-dependent manner, remains obscure. A closed cranial window was prepared in 15 pentobarbital-anesthetized adult rabbits. The cerebral pial arteriolar alteration induced by either isoflurane (n = 8) or sevoflurane (n = 7) at 0 (before volatile anesthetic), 0.33, 0.67, and 1.0 minimum alveolar concentration (MAC) was measured under three consecutive conditions: intravenous infusion with saline, with ketamine, and with ketamine plus l-arginine. Ketamine reduced the vasodilation induced by 0.67 (120 +/- 9% versus 113 +/- 9%; P <.05) and 1.0 MAC isoflurane (136 +/- 11% versus 118 +/- 10%; P <.05), but l-arginine did not restore the isoflurane-induced cerebral vasodilation. In rabbits inhaling sevoflurane, the degree of cerebral vasodilator response was smaller than that by isoflurane, and the cerebral vasodilation was comparable whether in the presence or absence of ketamine (with or without l-arginine). In conclusion, ketamine reduces isoflurane-induced cerebral vasodilation, apparently independently of nitric oxide formation, while sevoflurane-induced cerebral vasodilation is not significantly affected by ketamine.

L-arginine and nitroglycerin restore hypercapnia-induced cerebral vasodilation in rabbits after its attenuation by ketamine.

UNLABELLED: Although it has been reported that ketamine attenuates hypercapnia-induced cerebral vasodilation, the mechanism remains unknown. Because nitric oxide is involved in cerebral CO2 reactivity, we studied the effects of L-arginine and nitroglycerin on ketamine-mediated attenuation of vascular responses to hypercapnia. Under pentobarbital anesthesia, 16 rabbits underwent closed cranial window preparation. Hypercapnic challenges were repeated after IV saline, ketamine (10 mg/kg, followed by 20 mg x kg(-1) x h(-1)), or ketamine plus either L-arginine (150 mg/kg, followed by 100 mg x kg(-1) x h(-1); n = 8) or nitroglycerin (5 microg x kg(-1) x min(-1) infusion; n = 8). Ketamine reduced hypercapnia-induced cerebral vasodilation (1.27%/mm Hg +/- 0.45%/mm Hg [saline] versus 0.82%/mm Hg +/- 0.53%/mm Hg [ketamine]: P < 0.05), but L-arginine restored reactivity (1.28%/mm Hg +/- 0.73%/mm Hg: P < 0.05 versus ketamine), as did nitroglycerin (1.14%/mm Hg +/- 0.73%/mm Hg [saline] versus 0.56%/mm Hg +/- 0.63%/mm Hg [ketamine]: P < 0.05, and 1.15%/mm Hg +/- 0.74%/mm Hg [ketamine plus nitroglycerin]: P < 0.05 versus ketamine). This indicates that ketamine attenuates cerebral CO2 reactivity, at least in part, via suppression of nitric oxide-cyclic guanosine monophosphate mechanisms in the cerebral vasculature. IMPLICATIONS: The attenuation of cerebral vasodilation to hypercapnia seen under ketamine anesthesia is reversed by L-arginine or nitroglycerin infusion.