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Biomedical subjects

Koichi Inoue

Publications and source records attributed to Koichi Inoue.

54 records · Page 3Linked to original sources

The validation of column-switching LC/MS as a high-throughput approach for direct analysis of di(2-ethylhexyl) phthalate released from PVC medical devices in intravenous solution.

Health Canada reported recently that medical devices containing di(2-ethylhexyl) phthalate (DEHP) should not be used in the clinical treatment of infants, young boys, pregnant women, and nursing mothers. The risk assessment of DEHP released from PVC medical devices is an important issue for hospitalized patients. In this study, a simple, accurate, low-contamination and high-throughput analytical technique for the determination of DEHP in intravenous (IV) solution was developed using column-switching liquid chromatography/mass spectrometry (LC/MS) with an extraction mini-column. The sample preparation for on-line extraction involved simply mixing IV solution with internal standard as DEHP-d(4) in LC glass vials. The IV fat emulsion drug sample cannot be analyzed directly, hence this sample spiked with DEHP-d(4) solution was extracted by hexane and measured by column-switching LC/MS yielding an average recovery of 92.2% (C.V.=7.8%, n=5). A linear response was found for a variety of drugs tested within the validated range of 0.1 or 0.5-10 microg/ml with correlation coefficients (r) greater than 0.99. These results suggest that this method can assay background exposure to DEHP released from PVC medical devices in the patients. The method was applied to various IV solution samples to establish the first screening method for DEHP released from medical devices with respect to their safety.

Chromatography, High Pressure Liquid↗

Determination of uric acid in human saliva by high-performance liquid chromatography with amperometric electrochemical detection.

The aim of the present study is to establish a highly sensitive method for the determination of uric acid (UA) in human saliva. The monitoring of UA levels in less invasive biological samples such as saliva is suggested for the diagnosis and therapy of gout, hyperuricemia, and the Lesch-Nyhan syndrome, and for detecting such conditions as alcohol dependence, obesity, diabetes, high cholesterol, high blood pressure, kidney disease, and heart disease. Reversed-phase high-performance liquid chromatography with electrochemical detection (HPLC-ED) was employed for the determination of UA obtained by solid-phase extraction from saliva. To quantify UA, we compared the ED efficiencies of an amperometric ED (Ampero-ED) with a single electrode and a coulometric ED (Coulo-ED) with a multiple electrode array. The results showed that the detection limits (S/N=3) were 3 nM for Ampero-ED and 6 nM for Coulo-ED, and the linearity of the calibration curves of 60-6000 nM had correlation coefficients exceeding 0.999. In addition, the total analytical time was 10 min. In the sample preparation of UA in saliva, an Oasis MAX solid-phase cartridge was used. The recoveries of UA spiked at 0.6 and 3 microM in saliva were above 95% with a relative standard deviation (RSD) of less than 15%. Therefore, the present method may be used in the routine and diagnostic determination of UA in human saliva.

Chromatography, High Pressure Liquid↗

Column-switching high-performance liquid chromatography electrospray mass spectrometry coupled with on-line of extraction for the determination of mono- and di-(2-ethylhexyl) phthalate in blood samples.

A novel method based on column-switching high-performance liquid chromatography-electrospray mass spectrometry (LC-MS) coupled with an on-line extraction column containing conjugated avidin has been developed for direct injection analysis of di(2-ethylhexyl) phthalate (DEHP) and its metabolite, mono(2-ethylhexyl) phthalate (MEHP), in blood samples. The sample preparation for on-line extraction involved the mixing of blood samples with internal standards, DEHP-d(4) and MEHP-d(4), in LC glass vials. A linear response was found for column-switching LC-MS when tests were conducted within the validated range of 25 to 1000 ng mL(-1) for DEHP and 5 to 1000 ng mL(-1) for MEHP, with correlation coefficients (r) greater than 0.999. In addition, the recoveries of DEHP and MEHP from human plasma were calculated by using this method with on-line extraction, yielding recoveries of up to 91.2% (RSD<5%). We measured the background levels of DEHP and MEHP in six human plasma samples from healthy volunteers and three fetal bovine serum samples for cell-line culture. DEHP and MEHP were not detected in all human plasma samples (N.D. is <25 ng mL(-1) for DEHP, and N.D. is <5.0 ng mL(-1) for MEHP). In contrast, high DEHP contamination of commercially available fetal bovine serum samples was found by this method.

Adult↗

Optimal temperature of continuous lidocaine perfusion for the heart preservation.

OBJECTIVE: During cardiovascular surgery, lidocaine is administered to the cardioplegic system to stabilize cell membranes and prevent arrhythmia. Lidocaine is also commonly used in hypothermia. Both lidocaine and hypothermia are myocardially protective. Under normothermia, lidocaine displays its full pharmacological effects, which are apt, however, to be suppressed under hypothermia. We conducted experiments to determine the optimal temperature for myocardial protection in continuous lidocaine cardioplegia. METHODS: In Langendorff mode, rat hearts were continuously perfused with 1 mMol/l of lidocaine solution at 36 +/- 0.5 degrees C (Group A), 24 +/- 0.5 degrees C (Group B), or 7 +/- 0.5 degrees C (Group C) during preservation. Cardiac function and intracellular calcium concentration were measured during both preservation and reperfusion. Heat shock protein 70 (HSP70) was subsequently analyzed by Western blotting. RESULTS: Rapid cardiac arrest was obtained in Groups A and C. Heart rate recovery was good and ultimately the best in Group B, but worst in Group A. During lidocaine perfusion, the volume of coronary perfusion flow decreased gradually in all groups. After reperfusion, Group A showed only a slight increase in coronary perfusion, While Groups B and C showed a marked increase. Left ventricular contractility showed good recovery in all groups. The calcium concentration increased slightly in Group A, but decreased in Groups B and C. No calcium overload was evident in Group A. The same HSP70 level was detected in all groups. CONCLUSION: Lidocaine used in normothermia does not decrease cardiac metabolism or oxygen consumption, and displays full pharmacological effectiveness in preventing ischemic injury. We found 36 degrees C to be the optimal temperature for heart preservation by coronary perfusion with lidocaine cardioplegia.

Animals↗

Intracellular calcium increasing at the beginning of reperfusion assists the early recovery of myocardial contractility after diltiazem cardioplegia.

OBJECTIVES: We investigated the ability of diltiazem to prevent myocardial injury by assessing heart function and intracellular calcium concentrations before and after ischemia-reperfusion. METHOD: Isolated rat hearts underwent cardioplegia using the Langendorff perfusion model and were subjected to normothermic global ischemia for 60 minutes. The recovery rates for the heart function (heart rate, coronary flow, left ventricular systolic pressure) after reperfusion were monitored, and the intracellular Ca concentration was measured during ischemia and during the following reperfusion. Experimental groups were divided into three groups according to the diltiazem concentration used in the cardioplegic solution (potassium 20 mmol/l in Ringer's solution): (1) Group A: diltiazem 2.5 mg/l; (2) Group B: diltiazem 5 mg/l; and (3) Group C: no diltiazem. RESULTS: Intracellular calcium concentration increased in all 3 groups during ischemia, but was significantly lower in Group B compared to either Group A or Group C. The heart function was significantly higher for Group A than for Group B or Group C. The hearts in Group B displayed markedly poor recovery in contractility and in heart rate. CONCLUSIONS: Generally, a decrease in intracellular Ca concentration improves the heart function during ischemia and after reperfusion. However, this study showed that some increase in intracellular Ca at the beginning of reperfusion assisted the contractility of rat heart.

Animals↗

Suppression of defective ribosome assembly in a rbfA deletion mutant by overexpression of Era, an essential GTPase in Escherichia coli.

Era is a small GTP-binding protein and essential for cell growth in Escherichia coli. It consists of two domains: N-terminal GTP-binding and C-terminal RNA-binding KH domains. It has been shown to bind to 16S rRNAs and 30S ribosomal subunits in vitro. Here, we report that a precursor of 16S rRNA accumulates in Era-depleted cells. The accumulation of the precursors is also seen in a cold-sensitive mutant, E200K, in which the mutation site is located in the C-terminal domain. The major precursor molecule accumulated seems to be 17S rRNA, containing extra sequences at both 5' and 3' ends of 16S rRNA. Moreover, the amounts of both 30S and 50S ribosomal subunits relative to the amount of 70S monosomes increase in Era-depleted and E200K mutant cells. The C-terminal KH domain has a high structural similarity to the RbfA protein, a cold shock protein that also specifically associates with 30S ribosomal subunits. RbfA is essential for cell growth at low temperature, and a precursor of 16S rRNA accumulates in an rbfA deletion strain. The 16S rRNA precursor seems to be identical in size to that accumulated in Era mutant cells. Surprisingly, the cold-sensitive cell growth of the rbfA deletion cells was partially suppressed by overproduction of the wild-type Era. The C-terminal domain alone was not able to suppress the cold-sensitive phenotype, whereas Era-dE, which has a 10-residue deletion in a putative effector region of the N-terminal domain, functioned as a more efficient suppressor than the wild-type Era. It was found that Era-dE suppressed defective 16S rRNA maturation, resuming a normal polysome profile to reduce highly accumulated free 30S and 50S subunits in the rbfA deletion cells. These results indicate that Era is involved in 16S rRNA maturation and ribosome assembly.

Blotting, Northern↗

[Ischemic heart failure].

Ischemic heart failure is induced by myocardial ischemia, which is probably the commonest cause of left ventricular systolic dysfunction. Theoretically, there are two main strategies to treat the patients with ischemic heart failure; to retard progression of the dysfunction, and to relief and prevent myocardial ischemia. The management with angiotensin converting enzyme(ACE) inhibitor and beta-blocker improve the prognosis of ischemic heart failure by enhancing the left ventricular function and preventing coronary event. Spironolactone also seems to improve their prognosis. In contrast, treatments directed specifically at coronary arteries, such as antithrombotic agents and revascularization, have not been proven to be effective and safe to these patients yet. Large scale clinical trials are currently underway investigating the effect of treatment, such as aspirin, warfarin, clopidogrel and revascularization which are targeted to the coronary syndrome.

Adrenergic beta-Antagonists↗

A study of the myocardial protective effect of rapid cooling based on intracellular Ca, intracellular pH, and HSP70.

OBJECTIVE: It has been reported that rapid cooling of the heart during normothermic coronary circulation at reperfusion after ischemia promotes early recovery of cardiac function due to the positive inotropic effects on the myocardium produced by cooling. The aim of the present study was to investigate the myocardial protective effect of rapid cooling by measuring heat shock protein (HSP) levels and examining the relationship between cardiac function, intracellular Ca concentration, and intracellular pH after rapid cooling. METHODS: Isolated perfused rat hearts were subjected to ischemia for 60 minutes at a myocardial temperature of 37 degrees C. One group of hearts (group R) was subjected to 3 minutes of rapid cooling (</=4 degrees C) 3 minutes after reperfusion was started. The other hearts (group C) were not cooled. Myocardial protection was then compared in the two groups by measuring heart rate, coronary flow, left ventricular contraction, intracellular Ca concentration (fura-2 fluorescence), and intracellular pH (BCECF-AM fluorescence) and examining HSP70 by western blot. RESULTS: (1) Left ventricular contraction was 105+/-0.05% of the pre-ischemia value in group R after rapid cooling, whereas recovery was poor in group C (63+/-2%). (2) The intracellular Ca concentration in group R rose to 141+/-8% of the pre-ischemia value during ischemia, but decreased to 101+/-3% at reperfusion after rapid cooling. In group C, the Ca concentration was 144+/-4% of the pre-ischemia value during ischemia and rose further to 156+/-6% at reperfusion. (3) In group R, the intracellular pH was 6.85+/-0.05 during ischemia and rose after reperfusion was started, but after rapid cooling, decreased again to 7.43+/-0.02 after 60 minutes reperfusion. In group C, the pH was 6.88+/-0.06 during ischemia and rose to 7.90+/-0.09 60 minutes after reperfusion was started. (4) HSP70 was detected in both groups, but the concentration (luminescence) was lower in group R than in group C. CONCLUSION: Rapid cooling reduces myocardial injury by preventing intracellular Ca overload at reperfusion via inhibition of the Na(+)/Ca(2+) exchanger and also decreases the appearance of HSPs, the so-called homeostasis proteins. (Ann Thorac Cardiovasc Surg 2003; 9: 301-6)

Analysis of Variance↗

Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy.

Methylation at arginines has recently come to attention as a posttranslational modification of proteins, which is implicated in processes from signaling, transcriptional activation, to mRNA processing. Here we report that several proteins extracted from HeLa cells were methylated by PRMT1 (protein arginine N-methyltransferease 1) even on a nitrocellulose membrane, while proteins from Escherichia coli are not methylated with this protein. Screening PRMT1 substrates from a lambdagt11-HeLa cDNA library, we found that more than half of the 48 cDNA clones obtained encode putative RNA-binding proteins that have RGG (arginine-glycine-glycine) motifs, such as hnRNP R (heterogeneous nuclear ribonucleoprotein R) and hnRNP K. We cloned two novel arginine methylation substrates, ZF5 (zinc finger 5) and p137GPI (GPI-anchor protein p137), which do not possess typical RGG motifs. We also cloned a novel protein that has RGG motifs, but does not have any other RNA-binding motifs. We tentatively termed this clone SAMT1 (substrate of arginine methyl transferase 1). A(63-)VLD(-65) to AAA mutation of PRMT1 suppressed the methylation of recombinant SAMT1 and other RGG proteins in the HeLa extracts. This systematic screening of substrate proteins with the solid phase methylation reaction will contribute to identify new roles of PRMT family.

Amino Acid Motifs↗

Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5.

We isolated a mammalian gene whose expression transiently increased in response to intimal denudation of rabbit aorta. It was identical to a gene encoding a zinc transporter, ZNT5, reported very recently by others. Mice deficient for this gene showed poor growth and a decrease in bone density due to impairment of osteoblast maturation to osteocyte. More than 60% of male null mice died suddenly because of the bradyarrhythmias. Analysis of gene-expression profiles in murine hearts by means of an oligonucleotide microarray disclosed that a subset of genes encoding immediate-early response factors (IEGs) and heat shock proteins (HSPs) were down-regulated in Znt5-null mice. These results indicate that Znt5 protein plays an important role in maturation of osteoblasts and in maintenance of the cells involved in the cardiac conduction system, partly owing to dysregulated expression of IEGs and HSPs.

Amino Acid Sequence↗

Application of liquid chromatography-mass spectrometry to the quantification of bisphenol A in human semen.

The potential risks to human health and reproduction from the xenoestrogen bisphenol A (BPA) have not been well established. This is due in part to the absence of accurate analytical methods to quantify BPA in biological samples. In this study we establish an accurate, sensitive and selective analytical method for the quantification of BPA in human semen. To quantify BPA we compared the techniques of liquid chromatography-mass spectrometry (LC-MS) and enzyme-linked immunosorbent assay (ELISA). In addition we have taken steps to eliminate BPA contamination during sample extraction and preparation. Results show that the ELISA method gives an over-estimate of BPA concentration, which may be due, at least in part, to non-specific interactions with the BPA-antibodies. LC-MS gave much more accurate results and proved to be more sensitive with a detection limit of 0.5 ng ml(-1) compared to 2.0 ng ml(-1) by ELISA.

Benzhydryl Compounds↗

A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7 and inactivates the JNK MAPK pathway. Implication for the precise regulation of the particular MAPK pathway.

Mitogen-activated protein kinases (MAPKs) are activated in response to various extracellular stimuli, and their activities are regulated by upstream activating kinases and protein phosphatases such as MAPK phosphatases (MKPs). We report the identification and characterization of a novel MKP termed SKRP1 (SAPK pathway-regulating phosphatase 1). It contains an extended active site sequence motif conserved in all MKPs but lacks a Cdc25 homology domain. Immunoblotting analysis revealed that SKRP1 is constitutively expressed, and its transcripts of 4.0 and 1.0 kb were detected in almost tissues examined. SKRP1 was highly specific for c-Jun N-terminal kinase (JNK) in vitro and effectively suppressed the JNK activation in response to tumor necrosis factor alpha or thapsigargin. Endogenous SKRP1 was present predominantly in the cytoplasm and co-localized with JNK. However, SKRP1 does not bind directly to its target JNK, but co-precipitation of SKRP1 with the MAPK kinase MKK7, a JNK activator, was found in vitro and in vivo. Furthermore, we found that SKRP1 did not interfere with the co-precipitation of MKK7 with JNK. Together, our findings indicate that SKRP1 interacts with its physiological substrate JNK through MKK7, thereby leading to the precise regulation of JNK activity in vivo.

Amino Acid Sequence↗

Scaffold role of a mitogen-activated protein kinase phosphatase, SKRP1, for the JNK signaling pathway.

Stress-activated protein kinase (SAPK) pathway-regulating phosphatase 1 (SKRP1) has been identified as a member of the mitogen-activated protein kinase (MAPK) phosphatase (MKP) family that interacts physically with the MAPK kinase (MAPKK) MKK7, a c-Jun N-terminal kinase (JNK) activator, and inactivates the MAPK JNK pathway. Although these findings indicated that SKRP1 contributes to the precise regulation of JNK signaling, it remains to be elucidated how SKRP1 is integrated into this pathway. We report that SKRP1 also plays a scaffold role for the JNK signaling, judged by the following observations. SKRP1 selectively formed the stable complexes with MKK7 but not with MKK4 and biphasically regulated the MKK7 activity and MKK7-induced gene transcription in vivo. Co-precipitation analysis between SKRP1 and MKK7-activating MAPKK kinases (MAPKKKs) revealed that SKRP1 also interacted with the MAPKKK, apoptosis signal-regulating kinase 1 (ASK1), but not with MAP kinase kinase kinase 1 (MEKK1). Consistent with these findings, SKRP1 expression increased the ASK1-MKK7 complexes in a dose-dependent manner and specifically enhanced the activation of MKK7 by ASK1. Thus, our findings are, to our knowledge, the first evidence to show that an MKP also functions as a scaffold protein for the particular MAPK signaling.

3T3 Cells↗

Determination of phenolic xenoestrogens in water by liquid chromatography with coulometric-array detection.

A sensitive method for the simultaneous determination of phenolic xenoestrogens such as bisphenol A, 2,4-dichlorophenol, 4-tert,-butylphenol, 4-n2-pentylphenol, 4-n-hexylphenol, 4-n-heptylphenol, 4-octylphenol, 4-nonylphenol was developed using reversed-phase LC and coulometric-array detection. Stepwise gradient elution with phosphoric acid in water-acetonitrile was used. The calibration curves were linear in the range of 5.0 (or 10.0)-1000 ng ml(-1) with correlation coefficients of 0.9978-0.9999, the limits of detection were 0.01-0.02 ng ml(-1). Sample clean-up was performed by solid-phase extraction (SPE) using 3M Empore extraction disks. Three commercial sorbents, C18, SDB-XD (styrene-divinylbenzene polymer) and SDB-RPS (sulfonated styrene-divinylbenzene polymer) were compared. The highest recoveries were obtained with SDB-RPS. They were above 70% with a relative standard deviation of less than 15%. The proposed method was applied to the determination of phenolic xenoestrogens in various water samples.

Chromatography, Liquid↗

Characterization of estrogenic compounds in medical polyvinyl chloride tubing by gas chromatography-mass spectrometry and estrogen receptor binding assay.

BACKGROUND: In 2001, the U.S. Food and Drug Administration (FDA) convened to conduct a safety assessment of a plasticizer, di(2-ethylhexyl) phthalate (DEHP), released from polyvinyl chloride (PVC) medical devices. Hospitalized patients may be exposed to high concentrations of plasticizers, antioxidants, and chemical contaminants in PVC medical devices during blood transfusion or hemodialysis, thus, making them vulnerable to more potentially adverse effects of these chemicals than healthy people. At the same time, recently, the effect of endocrine-disrupting chemicals on hospitalized patients has attracted a great deal of attention. This study aims to investigate the harmful effects of estrogenic compounds in medical PVC tubing by two approaches of gas chromatography-mass spectrometry (GC-MS) and estrogen receptor (ER) binding assay. METHODS: Residual plasticizers, antioxidants, and chemical contaminants in PVC tubing were subjected to GC-MS in the full-scan mode with an original library for plastic additives. Such residual compounds in PVC tubing were screened at very low concentrations (10(-2)-10(5) nmol/l) to determine whether they competed with fluorescein-labeled estradiol for ER (alpha). RESULTS: DEHP, 2-ethylhexanol, butylated hydroxytoluene, and 4-nonylphenol (NP) were detected in medical PVC tubing. In addition, only NP in PVC tubing was found to bind with ER. CONCLUSIONS: The current study proves that the main residual chemical for estrogenic effect was NP in medical PVC tubing.

Butylated Hydroxytoluene↗

High-dose calcium stimulation test in a case of insulinoma masquerading as hysteria.

It is reported that some cases with insulinoma present with neuropsychiatric symptoms and are often misdiagnosed as psychosis. Here we report a case of insulinoma masquerading as hysteria, whose final diagnosis could be made using high-dose calcium stimulation test. A 28-yr-old woman was referred presenting with substupor, mutism, mannerism, restlessness, and incoherence. Laboratory examinations revealed hypoglycemia (33 mg/dL) and detectable insulin levels (9.7 microU/mL), suggesting the diagnosis of insulinoma. However, neither imaging studies nor selective arterial calcium injection (SACI) test with a conventional dose of calcium (0.025 mEq/kg) indicated the tumor. High-dose calcium injection (0.05 mEq/kg) evoked insulin secretion when injected into superior mesenteric artery. A solitary tumor in the head of the pancreas was resected, and her plasma glucose returned to normal. Postoperatively, iv injection of secretin resulted in a normal response of insulin, which was not found preoperatively. This case suggests the usefulness of the SACI test with high-dose of calcium in the case of insulinoma when the standard dose fails to detect such a tumor.

Adult↗

Specific growth inhibition by acetate of an Escherichia coli strain expressing Era-dE, a dominant negative Era mutant.

Escherichia coli Era is a GTP binding protein and essential for cell growth. We have previously reported that an Era mutant, designated Era-dE, causes a dominant negative effect on the growth and the loss of the ability to utilize TCA cycle metabolites as carbon source when overproduced. To investigate the role of Era, the gene expression in the cells overproducing Era-dE was examined by DNA microarray analysis. The expression of lipA and nadAB, which are involved in lipoic acid synthesis and NAD synthesis, respectively, was found to be reduced in the cells overproducing Era-dE. Lipoic acid and NAD are essential cofactors for the activities of pyruvate dehydrogenase complex, 2-oxoglutarate dehydrogenase complex and glycine cleavage enzyme complex. The expression of numerous genes involved in dissimilatory carbon metabolism and carbon source transport was increased. This set of genes partially overlaps with the set of genes controlled by cAMP-CAP in E coli. Moreover, the growth defect of Era-dE overproduction was specifically enhanced by acetate but not by TCA cycle metabolites both in rich and synthetic media. Intracellular serine pool in Era-dE overproducing cells was found to be increased significantly compared to that of the cells overproducing wild-type Era. It was further found that even the wild-type E. coli cells not overproducing Era-dE became sensitive to acetate in the presence of serine in a medium. We propose that when Era-dE is overproduced, carbon fluxes to the TCA cycle and to C1 units become impaired, resulting in a higher cellular serine concentration. We demonstrated that such cells with a high serine concentration became sensitive to acetate, however the reason for this acetate sensitivity is not known at the present.

Acetates↗

Surgical treatment of atherosclerotic and dysplastic aneurysms of the extracranial internal carotid artery.

Atherosclerotic and dysplastic aneurysms of the extracranial internal carotid artery are rare in Japan. We have experienced only four cases since 1982. The patients were two men and two women with a mean age of 67 years (range 51 to 82 years). All four patients had a saccular type aneurysm; sizes ranged from 30 to 75 mm. Aneurysmectomy and end-to-end anastomosis of the internal carotid artery could be performed in two patients. One patient underwent aneurysmorrhaphy followed by primary closure of the internal carotid artery, and the remaining patient underwent aneurysmectomy followed by a prosthetic graft replacement (6 mm-PTFE graft). During aneurysm repair, simple arterial cross-clamping (time 18 to 57 min; mean +/- SD: 31.3 +/- 18.0 min) was used in all patients. During arterial clamping of the carotid artery in two patients, somatosensory evoked potentials and regional cerebral oxygen saturation detected by near-infrared spectroscopy remained within normal ranges. All patients survived without neurologic deficits. These findings indicate that intraluminal shunting may be unnecessary during aneurysm repair if the patient does not have obstructive disease in the contralateral carotid artery and if no somatosensory evoked potentials or regional cerebral oxygen saturation abnormalities occur during proximal arterial clamping. After aneurysmectomy, end-to-end anastomosis of the internal carotid artery is the preferred method of repair if the length of the distal internal carotid artery permits.

Aged↗