Biomedical subjects

H M Wei

Publications and source records attributed to H M Wei.

At least 19 recordsLinked to original sources

PubMed2001

Capsaicin and nonivamide as novel skin permeation enhancers for indomethacin.

The study was conducted in vitro to investigate the changes of indomethacin transdermal permeation pretreated by capsaicin and nonivamide, two compounds chemically similar to Azone. The combined effect of low frequency ultrasound (20 kHz) and enhancers on the indomethacin permeation was also evaluated. The experimental data demonstrated that capsaicin and nonivamide significantly enhanced the flux of indomethacin across nude mouse skin. Enhancement effects of both analogues were very similar and depended predominantly on the concentration tested. Histological examination coupled with visual scores indicated the safety of capsaicin and nonivamide on skin structure. Simultaneous application of ultrasound and enhancers significantly increased skin permeation of indomethacin compared with either ultrasound or enhancers alone. Better effect was obtained by the combination with capsaicin than nonivamide.

Animals↗

PubMed2001

[Significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma].

OBJECTIVE: To study the significance of the unbalanced expression of Th1/Th2 type cytokines in human glioma. METHODS: The gene expressions of Th1/Th2 type cytokines in 62 specimens of human glioma tissues, 4 glioma cell lines, peripheral blood mononuclear cell (PBMC) of 15 glioma patients, 5 specimens of normal adult brain tissue and 5 brain meningioma tissues were detected by semiquantitative reverse transcription polymerase chain reaction. IFN-gamma and IL-2 represent Th1 type cytokines. IL-4, IL-6, IL-10 and IL-13 represent Th2 type cytokines. RESULTS: There were obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01) and specimens of human glioma tissues (P < 0.01). The tendency of distinct expression of Th2 type cytokines in PBMC was also existent. There wasn't obvious discrepancy of the expression of two type cytokines in normal adult brain tissues and meningioma tissues. CONCLUSIONS: It is likely that the switching of Th1/Th2 type cytokines in gliomas as predominant expression of Th2 type cytokine genes is related to the origination of gliomas and the evasion of glioma cells from immune surveillance.

Adolescent↗

PubMed2001

[Influence of adjustment of balance of Th1/Th2 type cytokines on proliferation of glioma cells].

OBJECTIVE: To study the influence of adjustment of balance of Th1/Th2 by external cytokines on proliferation of glioma cells. METHODS: The gene expressions of Th1/Th2 type cytokines in C6, 9L, U251 and SHG44 glioma cells were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). After the cells were induced with IFN-gamma + IL-4 McAb and IL-4 + IFN-gamma McAb respectively, we isolated the total RNA to proceed RT-PCR again. The evaluation of cell proliferation was proceeded by MTT assay method. RESULTS: There was obviously predominant expression of Th2 type cytokines in glioma cell lines (P < 0.01). The expression intensity of IFN-gamma was improved in IFN-gamma + IL-4 McAb groups and Th2 type cytokines were enhanced in IL-4 + IFN-gamma McAb groups. IFN-gamma and IL-4 McAb could cause the switch from Th2 to Th1, and could remarkably inhibit the proliferation of glioma cells in a dose-dependent way (P < 0.01). On the other hand, IL-4 and IFN-gamma McAb could strengthen the switch of Th2, and might stimulate the glioma cell growth, also in a dose-dependent way (P < 0.01). CONCLUSIONS: There is a Th2 preponderance in glioma cells. IFN-gamma and IL-4 McAb could regulate the switch from Th2 to Th0 or Th1, and inhibit the proliferation of glioma cells.

Antibodies, Monoclonal↗

PubMed2001

[Differentiation of natural killer cells into two functional subsets: NKh1 and NKh2].

OBJECTIVE: To verify the presence of functional subsets of natural killer cells based on the cytokine production. METHODS: NK cells were purified and cultured in complete RPMI1640 medium in the presence of either IFN gamma + anti-IL-4(classical Th1 polarization) or IL-4 + anti-IFN gamma (classical Th2 polarization) for three days, and then were collected and detected for type I/type II cytokines by RT-PCR method. RESULTS: NK cells were purified from 15 healthy donors, over 70% purity of NK cells were determined by flow cytometry. NK cells in peripheral blood expressed high level of type I cytokines, mainly IFN gamma, but low level of type II cytokines such as IL-10 and IL-13, IL-4 was not produced by NK cells. Cells cultured in IFN gamma + anti-IL-4 condition exhibited significantly increased level of IFN gamma, unchanged IL-2, and decreased type II cytokines. Cells grew in IL-4 + anti-IFN gamma condition exhibited increased IL-10 and IL-13, and decreased IFN gamma expressions. CONCLUSIONS: Based on the cytokine production, NK cells may be divided into two functional subsets in the same manner as that of T lymphocytes(e.g. Th1/Th2): NKh1 and NKh2. The biological characterization and phenotypic marker are under investigate.

Cells, Cultured↗

PubMed1999

X-linked adrenoleukodystrophy: genes, mutations, and phenotypes.

X-linked adrenoleukodystrophy (X-ALD) is a complex and perplexing neurodegenerative disorder. The metabolic abnormality, elevated levels of very long-chain fatty acids in tissues and plasma, and the biochemical defect, reduced peroxisomal very long-chain acyl-CoA synthetase (VLCS) activity, are ubiquitous features of the disease. However, clinical manifestations are highly variable with regard to time of onset, site of initial pathology and rate of progression. In addition, the abnormal gene in X-ALD is not the gene for VLCS. Rather, it encodes a peroxisomal membrane protein with homology to the ATP-binding cassette (ABC) transmembrane transporter superfamily of proteins. The X-ALD protein (ALDP) is closely related to three other peroxisomal membrane ABC proteins. In this report we summarize all known X-ALD mutations and establish the lack of an X-ALD genotype/phenotype correlation. We compare the evolutionary relationships among peroxisomal ABC proteins, demonstrate that ALDP forms homodimers with itself and heterodimers with other peroxisomal ABC proteins and present cDNA complementation studies suggesting that the peroxisomal ABC proteins have overlapping functions. We also establish that there are at least two peroxisomal VLCS activities, one that is ALDP dependent and one that is ALDP independent. Finally, we discuss variable expression of the peroxisomal ABC proteins and ALDP independent VLCS in relation to the variable clinical presentations of X-ALD.

Adrenoleukodystrophy↗

PubMed1998

Gene redundancy and pharmacological gene therapy: implications for X-linked adrenoleukodystrophy.

As more functional redundancy in mammalian cells is discovered, enhanced expression of genes involved in alternative pathways may become an effective form of gene therapy. X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder with impaired very-long-chain fatty acid metabolism. The X-ALD gene encodes a peroxisomal membrane protein (ALDP) that is part of a small family of related peroxisomal membrane proteins. We show that 4-phenylbutyrate treatment of cells from both X-ALD patients and X-ALD knockout mice results in decreased levels of and increased beta-oxidation of very-long-chain fatty acids; increased expression of the peroxisomal protein ALDRP; and induction of peroxisome proliferation. We also demonstrate that ALDP and ALDRP are functionally related, by ALDRP cDNA complementation of X-ALD fibroblasts. Finally, we demonstrate the in vivo efficacy of dietary 4-phenylbutyrate treatment through its production of a substantial reduction of very-long-chain fatty acid levels in the brain and adrenal glands of X-ALD mice.

ATP Binding Cassette Transporter, Subfamily D↗

PubMed1996

Cyclic GMP-phosphodiesterase inhibition does not alter cerebral oxygen consumption.

The effect of zaprinast, a cyclic guanosine monophosphate inhibitor, on the level of cyclic GMP and cerebral O2 consumption was determined. Anesthetized male Long-Evans rats were divided into a control group (n = 15) and a zaprinast treated group (n = 15). Vehicle was applied topically to the left cortex and 3*10-3 M zaprinast was applied to the right cortex. A saline treated control group was also studied. Regional cerebral blood flow was determined by [14C]-iodoantipyrine and regional 0(2) extraction was determined by microspectrophotometry. The level of cyclic GMP was measured by radioimmunoassay. There were no hemodynamic or blood gas differences between groups. The level of cyclic GMP was not significantly different between the right and left cerebral cortex of the control group (17.0 + or - 4.3 and 17.7 + or - 4.6 pmol/g). In the zaprinast treated group, there was a significant (46%) increase in the level of cyclic GMP in the zaprinast treated cortex (20.5 + or - 8.1) in comparison to the vehicle treated cortex (14.0 + or - 5.7). Zaprinast did not significantly alter cerebral blood flow. There were no significant differences in regional 0(2) extraction. The 0(2) consumption of the zaprinast treated cortex (8.0 + or - 3.3 ml O(2)*min(-1)*100 g(-1)) was not different from that of the vehicle ) treated cortex (7.0 + or - 2.9) or those of the control group. Thus, our data indicated that the increased level of cyclic GMP had no significant effect on cerebral oxygen consumption.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1996

Cerebral microregional oxygen balance during chronic versus acute hypertension in middle cerebral artery occluded rats.

This study was performed to compare microregional 0(2) supply and consumption balance in spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY), and in phenylephrine-induced acutely hypertensive WKY (WKY + ph) rats. Under isoflurane anesthesia, a middle cerebral artery (MCA) of SHR (n = 7) and WKY (n = 14) rats was occluded. Seven of the WKY rats were infused with phenylephrine (WKY + ph) to keep the mean arterial pressure (MAP) at the same level as that of the SHR. In all animals, 1 h after MCA occlusion, regional cerebral blood flow (rCBF) was determined using an autoradiographic technique, and microregional arterial and venous 02 saturations were determined using microspectrophotometry. MAP was 76 +/- 4 (SD), 136 +/- 15, and 132 +/- 12 mm Hg for the WKY, WKY + ph, and SHR groups, respectively. All variables describing regional O2 balance and rCBF were similar between the SHR and the WKY groups in the ischemic cortex as well as in the contralateral cortex. With phenylephrine infusion, rCBF of both the ischemic cortex and the contralateral cortex were increased in the WKY group. The average 02 supply-to-consumption ratio in the ischemic cortex was higher in the WKY + ph than in the WKY or SHR group. In the ischemic cortex, heterogeneity of venous 02 saturation (SvO2), expressed as a coefficient of variation (CV = 100 X SD/mean), was significantly lower in the WKY + ph (18.3 +/- 2.4) group than in the SHR (30.5 +/- 11.8) or in the WKY (31.3 +/- 9.0) group. The number of veins with low 02 saturation (SvO2 < 40%) in the ischemic cortex was significantly lower in the WKY + ph than in the SHR or in the WKY group. Our data suggest that in chronically hypertensive animals, cerebrovascular adaptations enable the microregional 02 balance in focal ischemia to be maintained at a level similar to that of normotensive animals. However, in normotensive animals with focal cerebral ischemia, an acute increase of MAP improves microregional O2 balance.

Acute Disease↗

PubMed1996

Hydroxyethyl starch solution attenuates blood-brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats.

This study was performed to investigate whether a fraction of hydroxyethyl starch macromolecules, prepared from pentastarch and known as "Hes-Pz," with molecular weights of 100,000-1,000,000, protects against blood-brain barrier (BBB) disruption due to intracarotid injection of hyperosmolar mannitol. Rats were anesthetized with isoflurane, and retrograde catheterization of a unilateral eternal carotid artery was performed. Except for the Control group (n = 8), hemodilution was performed using lactated Ringer's solution LR group, n = 7), 6% hetastarch (HES group, n = 7), or 6% HES-Pz (HES-Pz group, n = 8) to reduce the hematocrit to about 23%. The BBB transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid was determined after a unilateral intracarotid injection of 25% mannitol. Blood pressure and hematocrit were similar in all groups. In the control group, Ki was increased significantly in the ipsilateral cortex (IC) where mannitol was injected (16.3 +/- 6.1 vs 4.1 +/- 1.4 microL.min-1) when compared with the contralateral cortex (CC). Ki was similar in the CC in all four groups. The Ki in the IC was significantly lower in the HES-Pz(6.4 +/- 3.5 microL.g-1.min-1) than in the Control, HES, or LR group (16.3 +/- 6.1, 19.0 +/- 12.9, 17.9 +/- 10.8 microL.g-1.min-1, respectively). Our data suggest that HES-Pz significantly attenuates disruption of the BBB caused by an injection of hyperosmolar mannitol.

Aminoisobutyric Acids↗

PubMed1996

Increased blood-brain permeability with hyperosmolar mannitol increases cerebral O2 consumption and O2 supply/consumption heterogeneity.

This study was performed to evaluate whether increasing the permeability of the blood-brain barrier by unilateral intracarotid injection of hyperosmolar mannitol would alter O2 consumption and the O2 supply/consumption balance in the ipsilateral cortex. Rats were anesthetized with 1.4% isoflurane using mechanical ventilation. Retrograde catheterization of a unilateral external carotid artery was performed to administer 25% mannitol at a rate of 0.25 ml/kg/s for 30 s. The blood-brain barrier transfer coefficient (K(i) of 14C-alpha aminoisobutyric acid was measured in one group (N = 7) after administering mannitol. Regional cerebral blood flow (rCBF), regional arterial and venous O2 saturation and O2 consumption were measured in another group using a 14C-iodoantipyrine autoradiographic technique and microspectrophotometry (N = 7). Vital signs were similar before and after administering mannitol. K(i) was significantly higher in the ipsilateral cortex (IC) (22.3 +/- 8.4 microliters/g/min) than in the contralateral cortex (CC) (4.4 +/-1.1). rCBF was similar between the IC (105 +/- 21 ml/g/min) and the CC (93 +/- 20). Venous O2 saturation was lower in the IC (43 +/- 7%) than in the CC (55 +/- 4%). The coefficient of variation (100 x SD/mean) of venous O2 saturation was significantly elevated in the IC (32.3) compared with the CC (18.2), indicating increased heterogeneity of O2 supply/consumption balance. O2 consumption was higher in the IC (9.6 +/- 3.0 ml O2/100 g/min) than in the CC (6.7 +/- 1.5). Our data suggested that increasing permeability of the blood-brain barrier increased cerebral O2 consumption and the heterogeneity of local O2 supply/consumption balance.

Animals↗

PubMed1995

Effect of nitroprusside on regional cerebral cyclic GMP, blood flow and O2 consumption in rat.

This investigation was conducted to test whether topical nitroprusside (NP), a cytosolic guanylate cyclase activator, would increase the level of cyclic GMP and alter O2 consumption or blood flow in the cerebral cortex of rats. Male Long-Evans rats were used in a control (n = 9), low dose NP (n = 13, 10(-3) M) or high dose NP (n = 12, 10(-2) M) group. Nitroprusside or saline was topically applied to the right side of the cerebral cortex and the left side was used as a control. The cyclic GMP level was determined in five rats in each group using a radioimmunoassay. In the other rats in each group, regional cerebral blood flow was measured by [14C]iodoantipyrine and regional arterial and venous O2 saturations were determined microspectrophotometrically. Nitroprusside significantly increased the cyclic GMP level from 21.4 +/- 12.0 pmol/g (contralateral cortex) to 52.2 +/- 36.7 pmol/g (NP treated cortex) in low dose nitroprusside group and from 19.9 +/- 22.6 pmol/g (contralateral cortex) to 58.5 +/- 15.1 pmol/g (NP treated cortex) in high dose nitroprusside group. High dose nitroprusside significantly increased cerebral blood flow from 80 +/- 11 ml.min-1.100 g (contralateral cortex) to 114 +/- 11 ml.min-1.100 g (NP treated cortex). However, there was no significant difference in O2 extraction and O2 consumption between the NP treated cortex and contralateral cortex in either the low or the high dose NP groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Mutational analysis of patients with X-linked adrenoleukodystrophy.

Adrenoleukodystrophy (ALD) is an X-linked neurodegenerative disorder characterized by elevated very long chain fatty acid (VLCFA) levels, reduced activity of peroxisomal VLCFA-CoA ligase, and variable phenotypic expression. A putative gene for ALD was recently identified and surprisingly encodes a protein (ALDP) that belongs to a family of transmembrane transporters regulated or activated by ATP (the ABC proteins). We have examined genomic DNA from ALD probands for mutations in the putative ALD gene. We detected large deletions of the carboxyl-terminal portion of the gene in 4 of 112 probands. Twenty-five of the ALD probands whose ALD genes appeared normal by Southern blot analysis were surveyed for mutations by Single Strand Conformation Polymorphism (SSCP) procedures and DNA sequence analysis. SSCP variants were detected in 22 probands and none in 60 X-chromosomes from normal individuals. Mutations were detected in all of the ALD probands. The mutations were distributed throughout the gene and did not correlate with phenotype. Approximately half were non-recurrent missense mutations of which 64% occurred in CpG dinucleotides. There was a cluster of frameshift mutations in a small region of exon 5, including an identical AG deletion in 7 unrelated probands. These data strongly support the supposition that mutations in the putative ALD gene result in ALD.

ATP Binding Cassette Transporter, Subfamily D, Mem↗

PubMed1995

Effects of CAS 754, a new nitric oxide donor, on regional cerebral blood flow in focal cerebral ischemia.

Nitric oxide (NO) plays an important role in regulating regional cerebral blood flow (rCBF). This study was performed to compare the effects of the NO donor, CAS 754, a sydnonimine derivative, and sodium nitroprusside (SNP) on rCBF in ischemic and nonischemic brain regions. Twenty-eight rats were anesthetized with 1.4% isoflurane and were mechanically ventilated. A middle cerebral artery (MCA) was occluded in each animal. In the CAS 754 group (n = 7), 40 min after MCA occlusion, 4-6 mg/kg of CAS 754 was administered intravenously (i.v.) to decrease the mean arterial blood pressure (MAP) to 55-60 mm Hg. In the SNP group (n = 7), an infusion of SNP was started to decrease the MAP to the same level as that of the CAS group. In the CAS-Ph group (n = 7), phenylephrine was infused after CAS754 had been administered in order to maintain the MAP at the control level (95-100 mm Hg). The remaining seven rats were used as a control group. rCBF was measured using 14C-iodoantipyrine in all four groups of animals 1 h after MCA occlusion (20 min after the start of drug administration). The average rCBF of the nonischemic brain regions (121 +/- 15 mL.min-1.100 g-1) was increased by 34% with CAS 754 (162 +/- 39 mL.min-1.100 g-1). However, SNP did not significantly change the average rCBF of the nonischemic brain regions (114 +/- 5 mL.min-1.100 g-1). Neither CAS 754 nor SNP significantly affected the rCBF of the ischemic cortex (control 51 +/- 7, CAS 61 +/- 13, SNP 53 +/- 18 mL.min-1.100 g-1). Phenylephrine infusion in the CAS 754-treated animals did not significantly affect the rCBF of the ischemic or nonischemic brain regions. In conclusion, our study demonstrated that CAS 754 was a more effective cerebral vasodilator than nitroprusside when administered systemically. In the ischemic cortex, neither CAS 754 nor nitroprusside improved rCBF Failure of CAS 754 to improve the rCBF of the ischemic cortex does not appear to be due to hypotension induced by CAS 754.

Animals↗

PubMed1995

Altered expression of ALDP in X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (ALD) is a neurodegenerative disorder with variable phenotypic expression that is characterized by elevated plasma and tissue levels of very long-chain fatty acids. However, the product of the gene defective in ALD (ALDP) is a membrane transporter of the ATP-binding cassette family of proteins and is not related to enzymes known to activate or oxidize fatty acids. We generated an antibody that specifically recognizes the C-terminal 18 amino acids of ALDP and can detect ALDP by indirect immunofluorescence. To better understand the mechanism by which mutations in ALDP lead to disease, we used this antibody to examine the subcellular distribution and relative abundance of ALDP in skin fibroblasts from normal individuals and ALD patients. Punctate immunoreactive material typical of fibroblast peroxisomes was observed in cells from seven normal controls and eight non-ALD patients. Of 35 ALD patients tested, 17 had the childhood-onset cerebral form of the disease, 13 had the milder adult phenotype adrenomyeloneuropathy, 3 had adrenal insufficiency only, and 2 were affected fetuses. More than two-thirds (69%) of all patients studied showed no punctate immunoreactive material. There was no correlation between the immunofluorescence pattern and clinical phenotype. We determined the mutation in the ALD gene in 15 of these patients. Patients with either a deletion or frameshift mutation lacked ALDP immunoreactivity, as expected. Four of 11 patients with missense mutations were also immunonegative, indicating that these mutations affected the stability or localization of ALDP. In the seven immunopositive patients with missense mutations, correlation of the location and nature of the amino acid substitution may provide new insights into the function of this peroxisomal membrane protein. Furthermore, the study of female relatives of immunonegative ALD probands may aid in the assessment of heterozygote status.

ATP Binding Cassette Transporter, Subfamily D, Mem↗

PubMed1994

Effects of topical methylene blue on cyclic GMP level, blood flow, and O2 consumption in focal cerebral ischaemia.

We hypothesized that a decrease in cyclic GMP, a second messenger in the glutamate-nitric oxide pathway, would reduce oxygen consumption and improve O2 balance in the ischaemic cerebral cortex. To test this hypothesis, a study was performed in unilateral middle cerebral artery occluded rats which were assigned to either a control or methylene blue (10(-3) M) group. Regional cerebral blood flow was determined using 14C-iodoantipyrine and regional arterial and venous O2 saturations were determined by microspectrophotometry (n = 6). Cyclic GMP level was measured by radioimmunoassay (n = 8). Guanylate cyclase and cyclic GMP-phosphodiesterase activities were determined in an additional set of control rats (n = 10). The cyclic GMP levels were not different between the ischaemic and contralateral areas in the control group. Compared to the cyclic GMP in the control ischaemic cortex, topical methylene blue significantly decreased the cyclic GMP level by 56% in the ischaemic cortex of the methylene blue group. Ischaemia did not alter the activities of guanylate cyclase but mildly decreased cyclic GMP-phosphodiesterase. The regional cerebral blood flow and O2 consumption in the control group were 50% and 32% lower than those in corresponding contralateral cortex. Topical methylene blue did not alter regional cerebral blood flow and O2 consumption in the ischaemic cortex. Our data showed that cyclic GMP is not a major controller on O2 supply or O2 consumption in the ischaemic brain.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1994

Effects of inhibition of nitric oxide synthase on blood-brain barrier transport in focal cerebral ischemia.

This study was performed to determine whether nitric oxide (NO) alters the transport of small hydrophilic molecules across the blood-brain barrier in focal cerebral ischemia by administering an NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) and by measuring the blood-brain barrier transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid (14C-AIB) in the rats with middle cerebral artery occluded under isoflurane anesthesia. L-NAME increased the mean arterial blood pressure from 91 +/- 9 to 134 +/- 13 mm Hg. The Ki of the ischemic cortex (ICO) was 26% higher than that of the contralateral cortex (CCO) in the control animals without the L-NAME treatment. However, in the L-NAME-treated animals, Ki was 33% lower in the ICO than in the CCO. The Ki of ICO in the L-NAME group was significantly lower (-54%) than that of the control group. L-NAME did not affect Ki significantly in the nonischemic brain regions. Our data demonstrate that focal ischemia increased Ki of 14C-AIB, but L-NAME significantly decreased the Ki in the focal ischemic area of the brain without causing significant changes in the nonischemic tissue. Our results suggest that NO may participate in increasing transport of small hydrophilic molecules across the blood-brain barrier in focal ischemia.

Amino Acid Oxidoreductases↗

PubMed1994

Nitric oxide synthase inhibition alters cerebral blood flow and oxygen balance in focal cerebral ischemia in rats.

BACKGROUND AND PURPOSE: This study investigated whether the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester (L-NAME) would alter blood flow and oxygen balance in the ischemic cerebrocortex of isoflurane-anesthetized Long-Evans rats. METHODS: Fifteen minutes after middle cerebral artery occlusion, L-NAME (1.5 mg/min per kilogram) was infused intravenously to the L-NAME group (n = 14), and normal saline was given to the control group (n = 14) for 45 minutes. In each group, regional cerebral blood flow was determined with [14C]iodoantipyrine, and arterial and venous oxygen saturations were determined by microspectrophotometry. RESULTS: In both groups regional cerebral blood flow of the ischemic cortex was significantly lower than that of the contralateral cortex ([mean +/- SD] 55 +/- 13 versus 110 +/- 29 mL/min per 100 g in the control group and 35 +/- 13 versus 90 +/- 24 mL/min per 100 g in the L-NAME group). Compared with the blood flow in the ischemic cortex of the control group, L-NAME significantly reduced ischemic blood flow by 36%. Venous oxygen saturation was significantly increased in the ischemic cortex (41 +/- 1% versus 44 +/- 3%) but decreased in the contralateral cortex (65 +/- 3% versus 61 +/- 4%) by L-NAME. Calculated ischemic cortical oxygen consumption in the L-NAME group was 39% lower than that in the corresponding control group, whereas the difference was only 11% in the contralateral sides between groups. In both groups, the ratio of oxygen supply to consumption was lower in the ischemic than in the nonischemic regions. In the ischemic cortex, this ratio was significantly lower in the control group than in the L-NAME group (1.7 +/- 0.1 versus 1.9 +/- 0.1). In contrast, the ratio tended to be decreased by L-NAME in nonischemic regions. CONCLUSIONS: These observations suggest that despite a decrease in cerebral blood flow, inhibition of nitric oxide synthesis mildly improves the oxygen supply and consumption balance in the ischemic cortex.

Amino Acid Oxidoreductases↗

PubMed1994

Effect of ketamine on heterogeneity of cerebral microregional venous O2 saturation in the rat.

Heterogeneity of microregional O2 supply and consumption balance exists in the brain. Previous studies have shown that anesthetics such as pentobarbital and isoflurane, decrease the heterogeneity of O2 saturation in the small veins of the brain. This study was performed to determine whether ketamine, an anesthetic, would alter this heterogeneity. Rats were anesthetized with isoflurane for the cannulation of the femoral artery and vein. Ninety minutes after discontinuation of isoflurane, they either received injections with ketamine 100 mg/kg intraperitoneally (IP) (n = 7) or were used as conscious controls (n = 7). In each rat, regional cerebral blood flow (rCBF) was determined by 14C-iodoantipyrine autoradiography, and microregional arterial and venous (diameter 20-100 microns) O2 saturation was measured by microspectrophotometry in the anterior cortex, posterior cortex, and pons. The average rCBF and O2 consumption were similar between the two groups in each brain region except in the anterior cortex, where the O2 consumption of the ketamine group was slightly higher than that of the conscious animals. The average regional O2 supply-to-consumption ratios were similar in the three brain regions in both of the groups. However, there was heterogeneity of the O2 saturation in small veins in all the brain regions that we studied. The coefficient of variation [CV = (SD/mean X 100] of venous O2 saturation of the ketamine group in the anterior cortex (19.8 +/- 7.2), in the posterior cortex (18.8 +/- 9.4), and in the pons (16.7 +/- 6.5) was not significantly different from that in the conscious animals (22.8 +/- 6.4, 23.1 +/- 5.3, and 15.7 +/- 6.4, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗