Sevoflurane and nitrous oxide anaesthesia suppresses heart rate variabilities during deliberate hypotension.

BACKGROUND AND OBJECTIVE: Despite the fact that both general anaesthetics and hypotensive drugs influence autonomic nervous activity, no study has yet examined the heart rate variability during deliberate hypotension and general anaesthesia. The aim of this was to clarify the heart rate variability changes during deliberate hypotension under sevoflurane-nitrous oxide anaesthesia. METHODS: Autonomic nervous system activity in patients (n=45) subjected to deliberate hypotension during sevoflurane in nitrous oxide and oxygen anaesthesia was investigated by a heart rate variability measurement. Three different types of hypotensive drugs, a calcium channel antagonist (nicardipine), a nitric oxide donor (nitroglycerin) and a vasodilatory prostaglandin (alprostadil), were used to induce hypotension. RESULTS: In all groups, low frequency power (sympathetic and parasympathetic indicator) and the ratio of low frequency to high frequency power (the LF/HF ratio, sympathetic indicator) were suppressed by induction of anaesthesia. In the control group, preanaesthesia low frequency power was 195 +/- 139 ms(2), the LF/HF ratio 10.3 +/- 5.7, during anaesthesia 5 +/- 9 ms(2), 0.6 +/- 0.8, respectively, P=0.0093, 0.0034, whereas high frequency power (parasympathetic indicator) was not significantly changed. In those patients receiving nicardipine or nitroglycerin during anaesthesia, these variables did not differ significantly from those in the control group. During prostaglandin E1 infusion, high frequency power was higher compared with the values in the other groups (17 +/- 12 ms(2) in the prostaglandin group, 7 +/- 6 ms(2) in the nicardipine group, 6 +/- 5 ms(2) in the nitroglycerin group and 6 +/- 4 ms(2) in the control group, respectively, P=0.0326, 0.0251, 0.0197). CONCLUSIONS: Sevoflurane in nitrous oxide and oxygen anaesthesia reduces sympathetic autonomic activity considerably, and the expected increases caused by hypotensive agents that occur in awake volunteers were not seen.

Thiazolidinedione- and tumor necrosis factor alpha-induced downregulation of peroxisome proliferator-activated receptor gamma mRNA in differentiated 3T3-L1 adipocytes.

Thiazolidinediones (TZDs) are antidiabetic insulin-sensitizing agents that bind to peroxisome proliferator-activated receptor gamma (PPARgamma) and have potent adipogenic effects on 3T3-L1 preadipocytes. In fully differentiated 3T3-L1 adipocytes, TZDs markedly decreased PPARgamma mRNA levels without reducing the expression of genes that are positively regulated by PPARgamma, such as adipocyte lipid-binding protein 2 (aP2) or lipoprotein lipase-(LPL). PPARgamma mRNA levels were also downregulated by tumor necrosis factor alpha (TNFalpha), an antiadipogenic cytokine. We propose that the downregulation of PPARgamma is not the common denominator of the metabolic effects of TZDs and TNFalpha on mature adipocytes.

The combination of a fiberoptic stylet and a McCoy laryngoscope facilitates tracheal intubation in difficult airway cases.

PURPOSE: Fiberoptic stylets are considered useful for difficult airway management. In the present study, we assessed the usefulness of a fiberoptic stylet when the stylet was used with a Macintosh or a McCoy laryngoscope. METHODS: Twenty-four patients, whose airways were graded as Cormack grade III, were studied. We compared the times required for tracheal intubation when the fiberoptic stylet was used with a Macintosh direct laryngoscope and when it was used with a McCoy laryngoscope. Cormack grade III was subdivided into IIIa (with distance between the epiglottis and the posterior wall of the pharynx) and IIIb (with no distance between the epiglottis and the posterior wall of the pharynx), according to the view of the vocal cords by the laryngoscope. RESULTS: The intubation time in grade IIIb patients, who were intubated by the concurrent use of the fiberoptic stylet and the McCoy laryngoscope (28 +/- 4 s), was not significantly different from that in grade IIIa patients (28 +/- 10 s). The intubation time in grade IIIb patients, who were intubated by the concurrent use of the fiberoptic stylet and the Macintosh laryngoscope (52 +/- 8 s), was significantly longer than that in grades IIIa (28 +/- 10 s; P < 0.01) or IIIb with the McCoy laryngoscope (28 +/- 4 s; P < 0.01). CONCLUSION: The combination of a new handy fiberoptic stylet and a McCoy laryngoscope facilitated tracheal intubation of patients whose airway had no distance between the epiglottis and the posterior wall of the pharynx in laryngoscopic vocal cord view.

Novel mutations in the microsomal triglyceride transfer protein gene causing abetalipoproteinemia.

Abetalipoproteinemia (ABL) is an inherited disease characterized by the virtual absence of apolipoprotein B (apoB)-containing lipoproteins from plasma. Only limited numbers of families have been screened for mutations in the microsomal triglyceride transfer protein (MTP) gene. To clarify the genetic basis of clinical diversity of ABL, mutations of the MTP gene have been screened in 4 unrelated patients with ABL. Three novel mutations have been identified: a frameshift mutation caused by a single adenine deletion at position 1389 of the cDNA, and a missense mutation, Asn780Tyr, each in homozygous forms; and a splice site mutation, 2218-2A-->G, in a compound heterozygous form. The frameshift and splice site mutations are predicted to encode truncated forms of MTP. When transiently expressed in Cos-1 cells, the Asn780Tyr mutant MTP bound protein disulfide isomerase (PDI) but displayed negligible MTP activity. It is of interest that the patient having the Asn780Tyr mutation, a 27-year-old male, has none of the manifestations characteristic of classic ABL even though his plasma apoB and vitamin E were virtually undetectable. These results indicated that defects of the MTP gene are the proximal cause of ABL.

Absence of ACAT-1 attenuates atherosclerosis but causes dry eye and cutaneous xanthomatosis in mice with congenital hyperlipidemia.

Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes esterification of cellular cholesterol. To investigate the role of ACAT-1 in atherosclerosis, we have generated ACAT-1 null (ACAT-1-/-) mice. ACAT activities were present in the liver and intestine but were completely absent in adrenal, testes, ovaries, and peritoneal macrophages in our ACAT-1-/- mice. The ACAT-1-/- mice had decreased openings of the eyes because of atrophy of the meibomian glands, a modified form of sebaceous glands normally expressing high ACAT activities. This phenotype is similar to dry eye syndrome in humans. To determine the role of ACAT-1 in atherogenesis, we crossed the ACAT-1-/- mice with mice lacking apolipoprotein (apo) E or the low density lipoprotein receptor (LDLR), hyperlipidemic models susceptible to atherosclerosis. High fat feeding resulted in extensive cutaneous xanthomatosis with loss of hair in both ACAT-1-/-:apo E-/- and ACAT-1-/-:LDLR-/- mice. Free cholesterol content was significantly increased in their skin. Aortic fatty streak lesion size as well as cholesteryl ester content were moderately reduced in both double mutant mice compared with their respective controls. These results indicate that the local inhibition of ACAT activity in tissue macrophages is protective against cholesteryl ester accumulation but causes cutaneous xanthomatosis in mice that lack apo E or LDLR.

Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity.

Hormone-sensitive lipase (HSL) is known to mediate the hydrolysis not only of triacylglycerol stored in adipose tissue but also of cholesterol esters in the adrenals, ovaries, testes, and macrophages. To elucidate its precise role in the development of obesity and steroidogenesis, we generated HSL knockout mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutant HSL allele (HSL-/-) were superficially normal except that the males were sterile because of oligospermia. HSL-/- mice did not have hypogonadism or adrenal insufficiency. Instead, the testes completely lacked neutral cholesterol ester hydrolase (NCEH) activities and contained increased amounts of cholesterol ester. Many epithelial cells in the seminiferous tubules were vacuolated. NCEH activities were completely absent from both brown adipose tissue (BAT) and white adipose tissue (WAT) in HSL-/- mice. Consistently, adipocytes were significantly enlarged in the BAT (5-fold) and, to a lesser extent in the WAT (2-fold), supporting the concept that the hydrolysis of triacylglycerol was, at least in part, impaired in HSL-/- mice. The BAT mass was increased by 1.65-fold, but the WAT mass remained unchanged. Discrepancy of the size differences between cell and tissue suggests the heterogeneity of adipocytes. Despite these morphological changes, HSL-/- mice were neither obese nor cold sensitive. Furthermore, WAT from HSL-/- mice retained 40% of triacylglycerol lipase activities compared with the wild-type WAT. In conclusion, HSL is required for spermatogenesis but is not the only enzyme that mediates the hydrolysis of triacylglycerol stored in adipocytes.

Embryonic lethality and defective neural tube closure in mice lacking squalene synthase.

Squalene synthase (SS) catalyzes the reductive head-to-head condensation of two molecules of farnesyl diphosphate to form squalene, the first specific intermediate in the cholesterol biosynthetic pathway. We used gene targeting to knock out the mouse SS gene. The mice heterozygous for the mutation (SS+/-) were apparently normal. SS+/- mice showed 60% reduction in the hepatic mRNA levels of SS compared with SS+/+ mice. Consistently, the SS enzymatic activities were reduced by 50% in the liver and testis. Nevertheless, the hepatic cholesterol synthesis was not different between SS+/- and SS+/+ mice, and plasma lipoprotein profiles were not different irrespective of the presence of the low density lipoprotein receptor, indicating that SS is not a rate-limiting enzyme in the cholesterol biosynthetic pathway. The mice homozygous for the disrupted SS gene (SS-/-) were embryonic lethal around midgestation. E9.5-10.5 SS-/- embryos exhibited severe growth retardation and defective neural tube closure. The lethal phenotype was not rescued by supplementing the dams either with dietary squalene or cholesterol. We speculate that cholesterol is required for the development, particularly of the nervous system, and that the chorioallantoic circulatory system is not mature enough to supply the rapidly growing embryos with maternal cholesterol at this developmental stage.

[Anaphylactic reaction to aprotinin following topical use of biological tissue sealant].

Biological tissue sealant is used for facilitation of intra-operative hemostasis. It is composed of cryoprecipitated fibrinogen, bovine-thrombin and bovine-aprotinin. In this report, we describe a 38-yr-old woman in whom severe anaphylactic shock occurred immediately after the topical use of biological tissue sealant on the completion of modified radical mastectomy. The patient's past history and pre-operative laboratory values were unremarkable except for mild nasal allergy. Postoperative prick tests for bovine-serum, bovine-thrombin and bovine-aprotinin were positive. Total IgE level was normal. By the radioallergosolbent tests (RAST), specific IgE antibodies for aprotinin were elevated to the class 2 level. Drug induced lymphocyte stimulation tests (DLST) were negative. These indicated that the case was an aprotinin-induced anaphylaxis during general anaesthesia. The level of CH50, C4, C1q and C5 decreased in the serum sample immediately after the shock, but C3 was unchanged. It was considered to be a direct degradation of the complement by the proteolytic enzymes. Biological tissue sealant should be used cautiously bearing in mind the possibility of anaphylactic complication.

[Evaluation of buprenorphine hydrochloride suppositories for postoperative pain relief].

An analgesic is often administered upon the occurrence of pain following surgery. Buprenorphine hydrochloride suppository (0.2 mg) was given immediately postoperatively to patients who had undergone surgery under general anesthesia. Post-operative pain has been observed after 782 +/- 41 minutes (n = 148, mean +/- SE) in the patients with suppository and 127 +/- 18 minutes (n = 57) in the control group (P less than 0.01). Analgesics were given to 68% of the control group within 2 hours, while it was given to 14% of the study group. Further 57% of the latter did not complain of any pain after 20 hours. The pharmacokinetics of buprenorphine was studied in 7 patients. Intrarectal administration of 0.2 mg buprenorphine suppository just after surgery had a sufficient analgesic action and did not induce any adverse reactions of any clinical importance.