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Biomedical subjects

Tsuyoshi Akiyama

Publications and source records attributed to Tsuyoshi Akiyama.

At least 19 recordsLinked to original sources
PubMed2006

Hypothermia reduces ischemia- and stimulation-induced myocardial interstitial norepinephrine and acetylcholine releases.

Although hypothermia is one of the most powerful modulators that can reduce ischemic injury, the effects of hypothermia on the function of the cardiac autonomic nerves in vivo are not well understood. We examined the effects of hypothermia on the myocardial interstitial norepinephrine (NE) and ACh releases in response to acute myocardial ischemia and to efferent sympathetic or vagal nerve stimulation in anesthetized cats. We induced acute myocardial ischemia by coronary artery occlusion. Compared with normothermia (n = 8), hypothermia at 33 degrees C (n = 6) suppressed the ischemia-induced NE release [63 nM (SD 39) vs. 18 nM (SD 25), P < 0.01] and ACh release [11.6 nM (SD 7.6) vs. 2.4 nM (SD 1.3), P < 0.01] in the ischemic region. Under hypothermia, the coronary occlusion increased the ACh level from 0.67 nM (SD 0.44) to 6.0 nM (SD 6.0) (P < 0.05) and decreased the NE level from 0.63 nM (SD 0.19) to 0.40 nM (SD 0.25) (P < 0.05) in the nonischemic region. Hypothermia attenuated the nerve stimulation-induced NE release from 1.05 nM (SD 0.85) to 0.73 nM (SD 0.73) (P < 0.05, n = 6) and ACh release from 10.2 nM (SD 5.1) to 7.1 nM (SD 3.4) (P < 0.05, n = 5). In conclusion, hypothermia attenuated the ischemia-induced NE and ACh releases in the ischemic region. Moreover, hypothermia also attenuated the nerve stimulation-induced NE and ACh releases. The Bezold-Jarisch reflex evoked by the left anterior descending coronary artery occlusion, however, did not appear to be affected under hypothermia.

Acetylcholine↗
PubMed2006

Effects of Ca2+ channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats.

Although an axoplasmic Ca(2+) increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca(2+) channels in ACh release in the mammalian cardiac parasympathetic nerve is not clearly understood. Using a cardiac microdialysis technique, we examined the effects of Ca(2+) channel antagonists on vagal nerve stimulation- and ischemia-induced myocardial interstitial ACh releases in anesthetized cats. The vagal stimulation-induced ACh release [22.4 nM (SD 10.6), n = 7] was significantly attenuated by local administration of an N-type Ca(2+) channel antagonist omega-conotoxin GVIA [11.7 nM (SD 5.8), n = 7, P = 0.0054], or a P/Q-type Ca(2+) channel antagonist omega-conotoxin MVIIC [3.8 nM (SD 2.3), n = 6, P = 0.0002] but not by local administration of an L-type Ca(2+) channel antagonist verapamil [23.5 nM (SD 6.0), n = 5, P = 0.758]. The ischemia-induced myocardial interstitial ACh release [15.0 nM (SD 8.3), n = 8] was not attenuated by local administration of the L-, N-, or P/Q-type Ca(2+) channel antagonists, by inhibition of Na(+)/Ca(2+) exchange, or by blockade of inositol 1,4,5-trisphosphate [Ins(1,4,5)P(3)] receptor but was significantly suppressed by local administration of gadolinium [2.8 nM (SD 2.6), n = 6, P = 0.0283]. In conclusion, stimulation-induced ACh release from the cardiac postganglionic nerves depends on the N- and P/Q-type Ca(2+) channels (with a dominance of P/Q-type) but probably not on the L-type Ca(2+) channels in cats. In contrast, ischemia-induced ACh release depends on nonselective cation channels or cation-selective stretch activated channels but not on L-, N-, or P/Q type Ca(2+) channels, Na(+)/Ca(2+) exchange, or Ins(1,4,5)P(3) receptor-mediated pathway.

Acetylcholine↗
PubMed2006

Effect of sustained limb ischemia on norepinephrine release from skeletal muscle sympathetic nerve endings.

Acute ischemia has been reported to impair sympathetic outflow distal to the ischemic area in various organs, whereas relatively little is known about this phenomenon in skeletal muscle. We examined how acute ischemia affects norepinephrine (NE) release at skeletal muscle sympathetic nerve endings. We implanted a dialysis probe into the adductor muscle in anesthetized rabbits and measured dialysate NE levels as an index of skeletal muscle interstitial NE levels. Regional ischemia was introduced by microsphere injection and ligation of the common iliac artery. The time courses of dialysate NE levels were examined during prolonged ischemia. Ischemia induced a decrease in the dialysate NE level (from 19+/-4 to 2.0+/-0 pg/ml, mean+/-S.E.), and then a progressive increase in the dialysate NE level. The increment in the dialysate NE level was examined with local administration of desipramine (DMI, a membrane NE transport inhibitor), omega-conotoxin GVIA (CTX, an N-type Ca(2+) channel blocker), or TMB-8 (an intracellular Ca(2+) antagonist). At 4h ischemia, the increment in the dialysate NE level (vehicle group, 143+/-30 pg/ml) was suppressed by TMB-8 (25+/-5 pg/ml) but not by DMI (128+/-10 pg/ml) or CTX (122+/-18 pg/ml). At 6h ischemia, the increment in the dialysate NE level was not suppressed by the pretreatment. Ischemia induced biphasic responses in the skeletal muscle. Initial reduction of NE release may be mediated by an impairment of axonal conduction and/or NE release function, while in the later phase, the skeletal muscle ischemia-induced NE release was partly attributable to exocytosis via intracellular Ca(2+) overload rather than opening of calcium channels or carrier mediated outward transport of NE.

Animals↗
PubMed2005

Contribution of catechol O-methyltransferase to the removal of accumulated interstitial catecholamines evoked by myocardial ischemia.

Catechol O-methyltransferase (COMT) plays an important role for clearance of high catecholamine levels. Although myocardial ischemia evokes similar excessive catecholamine accumulation, it is uncertain whether COMT activity is involved in the removal of accumulated catecholamines evoked by myocardial ischemia. We examined how COMT activity affects myocardial catecholamine levels during myocardial ischemia and reperfusion. We implanted a dialysis probe into the left ventricular myocardial free wall and measured dialysate catecholamines levels in anesthetized rabbits. Dialysate catecholamine levels served as an index of myocardial interstitial catecholamine levels. We introduced myocardial ischemia by 60 min occlusion of the main coronary artery. The ischemia-induced dialysate catecholamines levels were compared with and without the pretreatment with entacapone (COMT inhibitor, 10 mg/kg, i.p.). Acute myocardial ischemia progressively increased dialysate catecholamine levels. Acute myocardial ischemia increased dialysate norepinephrine (NE) levels (20,453+/-7186 pg/ml), epinephrine (EPI) levels (1724+/-706 pg/ml), and dopamine (DA) levels (1807+/-800 pg/ml) at the last 15 min of coronary occlusion. Inhibition of COMT activity by entacapone augmented the ischemia-induced NE levels (54,306+/-6618 pg/ml), EPI levels (2681+/-567 pg/ml), and DA (3551+/-710 pg/ml) levels at the last 15 min of coronary occlusion. Myocardial ischemia evoked NE, EPI, and DA accumulation in the myocardial interstitial space. The inhibition of COMT activity augmented these increments in NE, EPI, and DA. These data suggest that cardiac COMT activity influences on the removal of accumulated catecholamine during myocardial ischemia.

Animals↗
PubMed2005

Vagal stimulation suppresses ischemia-induced myocardial interstitial norepinephrine release.

Although electrical vagal stimulation exerts beneficial effects on the ischemic heart such as an antiarrhythmic effect, whether it modulates norepinephrine (NE) and acetylcholine (ACh) releases in the ischemic myocardium remains unknown. To clarify the neural modulation in the ischemic region during vagal stimulation, we examined ischemia-induced NE and ACh releases in anesthetized and vagotomized cats. In a control group (VX, n = 8), occlusion of the left anterior descending coronary artery increased myocardial interstitial NE level from 0.46+/-0.09 to 83.2+/-17.6 nM at 30-45 min of ischemia (mean+/-SE). Vagal stimulation at 5 Hz (VS, n = 8) decreased heart rate by approximately 80 beats/min during the ischemic period and suppressed the NE release to 24.4+/-10.6 nM (P < 0.05 from the VX group). Fixed-rate ventricular pacing (VSP, n=8) abolished this vagally mediated suppression of ischemia-induced NE release. The vagal stimulation augmented ischemia-induced ACh release at 0-15 min of ischemia (VX: 11.1+/-2.1 vs. VS: 20.7+/-3.9 nM, P < 0.05). In the VSP group, the ACh release was not augmented. In conclusion, vagal stimulation suppressed the ischemia-induced NE release and augmented the initial increase in the ACh level. These modulations of NE and ACh levels in the ischemic myocardium may contribute to the beneficial effects of vagal stimulation on the heart during acute myocardial ischemia.

Acetylcholine↗
PubMed2005

Microdialysis separately monitors myocardial interstitial myoglobin during ischemia and reperfusion.

Direct monitoring of myoglobin efflux during ischemia and reperfusion has been limited because of inherent sample collection problems in the ischemic region. Recently, the cardiac dialysis technique has offered a powerful method for monitoring myocardial interstitial levels of low-molecular-weight compounds in the cardiac ischemic region. In the present study, we extended the molecular target to high-molecular-weight compounds by use of microdialysis probes with a high-molecular-mass cutoff and monitored myocardial interstitial myoglobin levels. A dialysis probe was implanted in the left ventricular free wall in anesthetized rabbits. The main coronary artery was occluded for 60 or 120 min. We examined the effects of myocardial ischemia and reperfusion on myocardial interstitial myoglobin levels. Interstitial myoglobin increased within 15 min of ischemia and continued to increase during 120 min of ischemia, whereas blood myoglobin increased at 45 min of ischemia. Lactate and myoglobin in the interstitial space increased during the same period. At 60 min of ischemia, reperfusion markedly accelerated interstitial myoglobin release. The interstitial myoglobin level was fivefold higher at 0-15 min of reperfusion than at 60-75 min of coronary occlusion. The dialysis technique permits earlier detection of myoglobin release and separately monitors myoglobin release during ischemia and reperfusion. Myocardial interstitial myoglobin levels can serve as an index of myocardial injury evoked by ischemia or reperfusion.

Animals↗
PubMed2005

Parahippocampal activation evoked by masked traumatic images in posttraumatic stress disorder: a functional MRI study.

Posttraumatic stress disorder (PTSD) has been widely studied, but its neural mechanism is still unclear. The purpose of this study is to identify dysfunctional areas in PTSD throughout the whole brain to help to elucidate the neural mechanisms of PTSD. Sixteen patients with PTSD and sixteen healthy controls participated in this study. Traumatic images under perceptual threshold including scenes of earthquakes, traffic accidents, ambulances, emergency rooms, and crimes were presented to the participants, and brain activation was measured using functional MRI. Functional brain images of both groups were evaluated with random effect analysis for the whole brain. In the control group, activation in the ventral frontoparietal areas correlated significantly with presentation of the masked traumatic stimuli. In the PTSD group, activation was not observed in these areas, but significant activation correlated with the masked traumatic stimuli in the parahippocampal region including the left parahippocampal gyrus and tail of the left hippocampus. These results suggest that in PTSD patients activation in the ventral frontoparietal network associated with visual attention processing is attenuated, while the left hippocampal area associated with episodic and autobiographical memory is abnormally easily activated. This pattern of activation corresponds well to the clinical characteristics of PTSD, in which even slight traumatic stimuli tend to induce intrusive recollection or flashbacks, despite a general decrease in attention and ability to concentrate.

Adult↗
PubMed2005

A photoelectronic switching device using a mixed self-assembled monolayer.

A cathodic-anodic biway photoelectronic device has been successfully constructed using a self-assembled monolayer (SAM). The SAM consists of two kinds of photofunctional thiol derivatives, a ruthenium complex-viologen linked compound (RuVS) and a phthalocyanine derivative (PcS), on a gold electrode. Structural characterization of the SAM has been carried out by absorption spectroscopy, cyclic voltammetry, and differential pulse voltammetry. Photocurrent responses were measured in the presence of methyl viologen (MV2+) and oxygen as electron acceptors and triethanolamine (TEOA) as a sacrificial reagent. For the SAM of RuVS alone, intramolecular electron transfer (ET) was superior to intermolecular ET, resulting in anodic photocurrents even in the presence of MV2+ and oxygen at 0 V vs Ag/AgCl. On the contrary, only cathodic photocurrents were observed at 0 V for the SAM of PcS alone. Photocurrents from the mixed SAM of RuVS and PcS were roughly the sum of individual photocurrents from RuVS and PcS. In fact, photocurrents from the mixed SAM of RuVS and PcS were observed in the anodic direction below approximately 550 nm, and in the cathodic direction above approximately 550 nm at 0 V vs Ag/AgCl. In the case of the mixed SAM of RuS (ruthenium complex disulfide) and PcS, only cathodic photocurrents were observed at 0 V vs Ag/AgCl, due to the lack of an intramolecular ET pathway. The results indicate that in the mixed SAM of RuVS and PcS both dyes can individually function for opposite photocurrent generation. We have also applied the mixed SAM as a photoelectronic logic device by using two LEDs (470 and 640 nm). The system clearly operated as an XOR logic device.

Journal Article↗
PubMed2005

Reliability and validity of TEMPS-A in a Japanese non-clinical population: application to unipolar and bipolar depressives.

BACKGROUND: In Japan, TEMPS-A has gathered much attention, because Kraepelin's concepts on "fundamental states" of mood disorder and temperaments have been widely respected. METHOD: TEMPS-A was translated into Japanese (and after the approval of the English back translation by H.S.A.), it was administered to 1391 non-clinical subjects, and 29 unipolar and 30 bipolar patients in remission. Of the non-clinical sample, 426 were readministered the instrument again in 1 month. A control group matched for gender and age was drawn from the non-clinical sample. RESULTS: Regarding test-retest reliability, Spearman's coefficients for depressive, cyclothymic, hyperthymic, irritable and anxious temperaments were 0.79, 0.84, 0.87, 0.81 and 0.87, respectively; regarding internal consistency, Cronbach's alpha coefficients were 0.69, 0.84, 0.79, 0.83 and 0.87, respectively. The unipolar and bipolar groups showed significantly higher depressive, cyclothymic and anxious temperament scores than the control group. Curiously, the bipolar group showed significantly lower hyperthymic score than the control group; irritable temperament scores showed no significant differences. Depressive, cyclothymic, irritable and anxious temperament scores showed significant correlations with each other. Between the unipolar and bipolar groups, there was little difference regarding the temperament scores. Also the inter-temperament correlations showed the same pattern in the unipolar and bipolar groups. LIMITATION: The clinically well cohort was 70% male. CONCLUSION: TEMPS-A showed a high reliability and validity (internal consistency) in a Japanese non-clinical sample. By and large, the hypothesized five temperament structure was upheld. Depressive, cyclothymic and anxious temperaments showed concurrent validity with mood disorder. Irritable temperament may represent a subtype of depressive, cyclothymic or anxious temperaments. There may be a temperamental commonality between unipolar and bipolar disorders. TEMPS-A will open new possibilities for international research on mood disorder and personality traits.

Adult↗
PubMed2005

The proposed factor structure of temperament and personality in Japan: combining traits from TEMPS-A and MPT.

BACKGROUND: In Japan, Kraepelin's descriptions on four "fundamental states" of manic depressive illness, the concepts of schizoid temperament by Kretschmer and obsessional and melancholic type temperament by Shimoda and Tellenbach have been widely accepted. This research investigates the construct validity of these temperaments through factor analysis. METHOD: TEMPS-A measured depressive, cyclothymic, hyperthymic and irritable temperaments and MPT rigidity, esoteric and isolation subscales measured, respectively, melancholic type and schizoid temperaments. Factor analysis was implemented with TEMPS-A alone and TEMPS-A and MPT combined data. RESULTS: With TEMPS-A alone analysis, Factor 1 included 1 depressive, 11 cyclothymic and 12 irritable temperament items with a factor loading higher than 0.4; Factor 2 included 1 depressive and 10 hyperthymic temperament items; and Factor 3 included 2 depressive temperament items only. With TEMPS-A and MPT combined data, Factor 1 included 3 depressive, 11 cyclothymic and 5 irritable temperament items with a factor loading higher than 0.4 (interpreted as the central cyclothymic tendency for all affective temperaments along Kretschmerian lines and accounting for 11.7% of the variance); Factor 2 included 6 hyperthymic temperament items (6.22% of variance); Factor 3 included 1 cyclothymic, 7 irritable and 1 schizoid temperament items (interpreted as the irritable temperament and accounting for 3.24% of the variance); Factor 4 included 1 depressive temperament and 5 melancholic type items (interpreted as the latter, accounting for 2.66% of the variance); Factor 5 included 5 depressive temperament items, along interpersonal sensitivity and passivity lines, and accounting for 2.31% of the variance; and Factor 6 included 4 schizoid temperament items accounting for 2.07% of the variance. LIMITATION: We did not use the Kasahara scale, which some believe to better capture the Japanese melancholic type. Sample was 70% male. CONCLUSION: These analyses confirm the factor validity of depressive, hyperthymic, cyclothymic and irritable temperaments (TEMPS-A), as well as the melancholic type and the schizoid temperament (MPT). Traits of the depressive and melancholic types emerge as rather distinct. Indeed, our results permit the delineation of an interpersonally sensitive type that "gives in to others" as the core features of the depressive temperament; this is to be contrasted with the higher functioning, perfectionistic, work-oriented melancholic type. Mood dysregulation is represented by the largest number of traits in this population. Contrary to a widely held belief that the melancholic type with its devotion to work and to others is the signature temperament in Japan, cyclothymic traits account for the largest variance in this nonclinical population. Hyperthymic temperament, melancholic type and schizoid temperaments appear largely independent of mood dysregulation. In this Japanese population, TEMPS-A may identify temperament constructs more comprehensively when implemented with melancholic type and schizoid temperament question items added to it. The proposed new Japanese Temperament and Personality (JTP) Scale has self-rated items divided into six subscales.

Adult↗
PubMed2005

Expression of mitochondria-related genes in lymphoblastoid cells from patients with bipolar disorder.

OBJECTIVES: Several studies have suggested mitochondrial abnormality in bipolar disorder. We reported the association of mitochondrial complex I subunit gene, NDUFV2 at 18p11, with bipolar disorder. A decrease in the mRNA expression of this gene was found in patients with bipolar disorder compared with controls. However, it was unclear whether only the NDUFV2 gene exhibited the decreased expression level in bipolar disorder. The aim of this study was to clarify the association of other nuclear-encoded complex I subunit genes and mitochondria-related genes with bipolar disorder. METHODS: We quantified the mRNA expression level of five nuclear-encoded mitochondrial complex I subunit genes located at the chromosomal regions linked with bipolar disorder other than NDUFV2, three complex IV subunit genes, and four mitochondrial transcription-related genes using a real-time quantitative reverse transcription polymerase chain reaction method in the lymphoblastoid cell lines from 21 patients with bipolar disorder and 11 controls. RESULTS: Decreased mRNA expression in patients with bipolar I disorder compared with control subjects was found in most of the complex I subunit genes. In addition, decreased expression levels of these genes correlated with that of NDUFV2. No statistically significant alterations of mRNA expression levels were found between bipolar patients and controls among two of three complex IV subunit genes and all transcription-related genes. CONCLUSIONS: Our study suggests that the decreased expression of NDUFV2 has a considerable effect on other subunit genes in the mitochondrial respiratory chain and presents further evidence of the biological significance of NDUFV2 in bipolar disorder.

Bipolar Disorder↗
PubMed2005

Mitochondrial DNA sequence analysis of patients with 'atypical psychosis'.

Although classical psychopathological studies have shown the presence of an independent diagnostic category, 'atypical psychosis', most psychotic patients are currently classified into two major diagnostic categories, schizophrenia and bipolar disorder, by the Diagnostic and Statistical Manual of Mental Disorders (4th edn; DSM-IV) criteria. 'Atypical psychosis' is characterized by acute confusion without systematic delusion, emotional instability, and psychomotor excitement or stupor. Such clinical features resemble those seen in organic mental syndrome, and differential diagnosis is often difficult. Because patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) sometimes show organic mental disorder, 'atypical psychosis' may be caused by mutations of mitochondrial DNA (mtDNA) in some patients. In the present study whole mtDNA was sequenced for seven patients with various psychotic disorders, who could be categorized as 'atypical psychosis'. None of them had known mtDNA mutations pathogenic for mitochondrial encephalopathy. Two of seven patients belonged to a subhaplogroup F1b1a with low frequency. These results did not support the hypothesis that clinical presentation of some patients with 'atypical psychosis' is a reflection of subclinical mitochondrial encephalopathy. However, the subhaplogroup F1b1a may be a good target for association study of 'atypical psychosis'.

Aged↗
PubMed2004

Association of mitochondrial complex I subunit gene NDUFV2 at 18p11 with bipolar disorder in Japanese and the National Institute of Mental Health pedigrees.

BACKGROUND: Linkage with 18p11 is one of the replicated findings in molecular genetics of bipolar disorder. Because mitochondrial dysfunction has been suggested in bipolar disorder, NDUFV2 at 18p11, encoding a subunit of the complex I, reduced nicotinamide adenine dinucleotide (NADH)ubiquinone oxidoreductase, is a candidate gene for this disorder. We previously reported that a polymorphism in the upstream region of NDUFV2, -602G> A, was associated with bipolar disorder in Japanese subjects; however, functional significance of -602G> A was not known. METHODS: We screened the further upstream region of NDUFV2. We performed a case-control study in Japanese patients with bipolar disorder and control subjects and a transmission disequilibrium test in 104 parent and proband trios of the National Institute of Mental Health (NIMH) Genetics Initiative pedigrees. We also performed the promoter assay to examine functional consequence of the -602G> A polymorphism. RESULTS: The -602G> A polymorphism was found to alter the promoter activity. We found that the other haplotype block surrounding -3542G> A was associated with bipolar disorder. The association of the haplotypes consisting of -602G> A and -3542G> A polymorphisms with bipolar disorder was seen both in Japanese case-control samples and NIMH trios. CONCLUSION: Together these findings indicate that the polymorphisms in the promoter region of NDUFV2 are a genetic risk factor for bipolar disorder by affecting promoter activity.

Adult↗
PubMed2004

Extraneuronal enzymatic degradation of myocardial interstitial norepinephrine in the ischemic region.

OBJECTIVE: Catechol O-methyltransferase (COMT) is believed to exert degradative action at high norepinephrine (NE) levels. Although COMT exists in cardiac tissues, the contribution of cardiac COMT activity to regional NE kinetics, particularly in ischemia-induced NE accumulation, remains unclear. We investigated the role of cardiac COMT in NE kinetics in the ischemic region. METHODS: We implanted a microdialysis probe into the left ventricular myocardium of anesthetized rabbits and induced myocardial ischemia by 60-min coronary artery occlusion. We monitored myocardial interstitial levels of NE and its metabolites in the presence and absence of a COMT inhibitor. We intraperitoneally administered entacapone (10 mg/kg) 120 min before control sampling. RESULTS: In control, entacapone increased interstitial dihydroxyphenylglycol (DHPG, intraneuronal NE metabolite by monoamine oxidase (MAO)) levels and decreased interstitial normetanephrine (NMN, extraneuronal NE metabolite by COMT) and 3-methoxy-4-hydroxyphenylglycol (MHPG, extraneuronal DHPG metabolite by COMT) levels, but did not change interstitial NE levels. Coronary occlusion increased NE levels to 165+/-48 nM at 45-60 min of occlusion. This increase was accompanied by increases in DHPG and NMN levels (11.3+/-1.1 and 9.3+/-1.3 nM at 45-60 min of occlusion). Entacapone augmented the ischemia-induced NE and DHPG responses (333+/-51 and 22.9+/-2.4 nM at 45-60 min of occlusion). In contrast, the ischemia-induced NMN response was suppressed by entacapone (2.0+/-0.4 nM at 45-60 min of occlusion). Reperfusion decreased interstitial NE levels and increased interstitial DHPG and NMN levels. Entacapone suppressed changes in NE and NMN levels, but augmented the increase in dialysate DHPG. CONCLUSION: Myocardial ischemia evoked increases in myocardial interstitial NE and NMN levels. COMT inhibition augmented the increase in NE (substrate of COMT) levels and suppressed the increase in NMN (metabolite by COMT) levels. In the ischemic heart, COMT contributes to the removal of accumulated NE in the myocardium.

Animals↗
PubMed2004

In vivo assessment of catechol O-methyltransferase activity in rabbit skeletal muscle.

With the use of microdialysis technique in the anesthetized rabbit, we examined the catechol O-methyltransferase (COMT) activity at the skeletal muscle interstitium. We implanted a dialysis probe into the adductor muscle, and monitored dialysate catecholamines and their metabolites with chromatogram-electrochemical detection. Administration of COMT inhibitor (entacapone) decreased dialysate 3-methoxy 4-hydroxyphenylglycol (MHPG) levels. Local administration of dihydroxyphenylglycol induced increases in dialysate MHPG levels. These increases in dialysate MHPG levels were suppressed by the addition of entacapone. The concentration of MHPG in the skeletal muscle dialysate corresponded to the COMT activity in the skeletal muscle. Furthermore, local administration of norepinephrine or epinephrine increased normetanephrine or metanephrine levels in dialysate but not MHPG levels. Skeletal muscle microdialysis with local administration of catecholamine offers a new method for in vivo assessment of regional COMT activity.

Animals↗