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Biomedical subjects

K Maeda

Publications and source records attributed to K Maeda.

At least 199 records · Page 11Linked to original sources
PubMed2000

Central action of insulin regulates pulsatile luteinizing hormone secretion in the diabetic sheep model.

This study tested the hypothesis that central mechanisms regulating luteinizing hormone (LH) secretion are responsive to insulin. Our approach was to infuse insulin into the lateral ventricle of six streptozotocin-induced diabetic sheep in an amount that is normally present in the CSF when LH secretion is maintained by peripheral insulin administration. In the first experiment, we monitored cerebrospinal fluid (CSF) insulin concentrations every 3-5 h in four diabetic sheep given insulin by peripheral injection (30 IU). The insulin concentration in the CSF was increased after insulin injection, and there was a positive relationship between CSF and plasma concentrations of insulin (r = 0.80, P < 0.01). In the second experiment, peripheral insulin administration was discontinued, and the sheep received either an intracerebroventricular (i.c.v.) infusion of insulin (12 mU/day in 2.4 ml saline) or saline (2.4 ml/day) for 5 days (n = 6) in a crossover design. The dose of insulin (i.c.v.) was calculated to approximate the increase in CSF insulin concentration found after peripheral insulin treatment. To monitor LH secretory patterns, blood samples were collected by jugular venipuncture at 10-min intervals for 4 h on the day before and 5 days after the start of i.c.v. insulin infusion. To monitor the increase in CSF insulin concentrations, a single CSF sample was collected one and four days after the start of the central infusion. The i.c.v. insulin infusion increased CSF insulin concentrations above those in saline-treated animals (P < 0.05) and maintained them at or above the peak levels achieved after peripheral insulin treatment. Central insulin infusion did not affect peripheral (plasma) insulin or glucose concentrations. LH pulse frequency in insulin-treated animals was greater than that in saline-treated animals (3.5 +/- 0.2 vs. 2.3 +/- 0.3 pulses/4 h, P < 0.01), but it was less than that during peripheral insulin treatment (4.8 +/- 0.2 pulses/4 h, P < 0.01). Our findings suggest that physiologic levels of central insulin supplementation are able to increase pulsatile LH secretion in diabetic sheep with low peripheral insulin. These results are consistent with the notion that central insulin plays a role in regulating pulsatile GnRH secretion.

Animals↗
PubMed2000

Quantitative measurement of local cerebral blood flow in the anesthetized mouse using intraperitoneal [14C]iodoantipyrine injection and final arterial heart blood sampling.

Autoradiographic measurement of local cerebral blood flow (CBF) with [14C]iodoantipyrine (IAP) is limited in mice by the difficulty in cannulating vessels and the blood loss for repeated blood sampling. The authors modified and validated the method to measure local CBF with [14C]IAP in mice by combining intraperitoneal tracer application with a single blood sampling from the heart at the end of the experiment. Experiments were carried out in male SV129 mice under halothane anesthesia. After intraperitoneal administration of 15 microCi [14C]IAP, arterial blood samples were collected repeatedly and anesthetized animals were immersed in liquid nitrogen. In addition, frozen blood from the heart was sampled to obtain the final blood [14C]radioactivity. Correlation analysis between the sampling time and [14C]radioactivity of the arterial blood revealed a highly significant linear relationship (P < 0.001, r = 0.978) and a lag time of the [14C]tracer in arterial blood of 3.3 +/- 0.6 seconds. [14C]radioactivity of the final arterial blood sample (444 +/- 264 nCi/mL) was almost equal to that of the heart blood (454 +/- 242 nCi/mL), and the absolute difference in each animal was 3.3 +/- 4.2% (mean +/- SD). The convolution integrals for the CBF calculation were determined either by integrating the radioactivity of individual arterial blood samples or by assuming a linear rise from [14C]tracer lag time after intraperitoneal [14C]IAP injection to the value measured in the blood sample from the frozen heart. Regional flow values calculated by the two methods differed by less than 11% (not significant). This method allows the quantitative measurement of local CBF in anesthetized mice without any vessel catheterization and will make mutant mice a more powerful tool to elucidate the molecular mechanisms of brain injuries by combining flow studies with molecular-biological methods.

Animals↗
PubMed2000

Dynamics of regional brain metabolism and gene expression after middle cerebral artery occlusion in mice.

The evolution of brain infarcts during permanent occlusion of the middle cerebral artery (MCA) was studied in mice using multiparametric imaging techniques. Regional protein synthesis and the regional tissue content of ATP were measured on adjacent cryostat sections at increasing intervals after vascular occlusion ranging from 1 hour to 3 days. The observed changes were correlated with the expression of the mRNA of hsp70, c-fos, c-jun, and junB, as well as the distribution of DNA double-strand breaks visualized by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL). One hour after MCA occlusion, the tissue volume with suppressed protein synthesis was distinctly larger than that in which ATP was depleted. With ongoing ischemia time, the ATP-depleted area gradually expanded and, within 1 day, merged with the region of suppressed protein synthesis. Expression of hsp70 mRNA occurred mainly in the penumbra (defined as the region of suppressed protein synthesis but preserved ATP), peaking at 3 hours after vascular occlusion. Expression of the immediate-early genes c-jun, c-fos, and junB increased both in the penumbra and the periinfarct normal tissue already at 1 hour after vascular occlusion, with slightly different regional and temporal patterns for each of these genes. DNA fragmentations were clearly confined to neurons; they appeared after 1 day in the infarct core (defined as the region of suppressed ATP) and never were detected in the penumbra. The late appearance of TUNEL after infarcts had reached their final size and the absence in the penumbra points against a major pathogenetic role of apoptosis. Permanent MCA occlusion in mice thus produces a gradually expanding infarct, the final size of which is heralded by the early inhibition of protein synthesis.

Adenosine Triphosphate↗
PubMed2000

Evolution of brain infarction after transient focal cerebral ischemia in mice.

The evolution of brain infarction after transient focal cerebral ischemia was studied in mice using multiparametric imaging techniques. One-hour focal cerebral ischemia was induced by occluding the middle cerebral artery using the intraluminal filament technique. Cerebral protein synthesis (CPS) and the regional tissue content of adenosine triphosphate (ATP) were measured after recirculation times from 0 hours to 3 days. The observed changes were correlated with the expression of the mRNAs of hsp-70, c-fos, and junB, as well as the distribution of DNA double-strand breaks, visualized by TUNEL. At the end of 1 hour of ischemia, protein synthesis was suppressed in a larger tissue volume than ATP in accordance with the biochemical differentiation between core and penumbra. Hsp70 mRNA was selectively expressed in the cortical penumbra, whereas c-fos and junB mRNAs were increased both in the lateral part of the penumbra and in the ipsilateral cingulate cortex with normal metabolism. During reperfusion after withdrawal of the intraluminal filament, suppression of CPS persisted except in the most peripheral parts of the middle cerebral artery territory, in which it recovered between 6 hours and 3 days. ATP, in contrast, returned to normal levels within 1 hour but secondarily deteriorated from 3 hours on until, between 1 and 3 days, the ATP-depleted area merged with that of suppressed protein synthesis leading to delayed brain infarction. Hsp70 mRNA, but not c-fos and junB, was strongly expressed during reperfusion, peaking at 3 hours after reperfusion. TUNEL-positive cells were detected from 3 hours on, mainly in areas with secondary ATP depletion. These results stress the importance of an early recovery of CPS for the prevention of ischemic injury and suggest that TUNEL is an unspecific response of delayed brain infarction.

Adenosine Triphosphate↗
PubMed2000

BodyMap: a collection of 3' ESTs for analysis of human gene expression information.

BodyMap is a collection of site-directed 3' expressed sequence tags (ESTs) (gene signatures, GSs) that contains the transcript compositions of various human tissues and was the first systematic effort to acquire gene expression data. For the construction of BodyMap, cDNA libraries were made, preserving abundance information and histologic resolutions of tissue mRNAs. By sequencing 164,000 randomly selected clones, 88,587 GSs that represent chromosomally coded transcripts have been collected from 51 human organs and tissues. They were clustered into 18,722 independent 3' termini from transcripts, and more than 3000 of these were not found among ESTs assembled in UniGene (Build 75). Assessment of the prevalence of polyadenylation signals and comparison with GenBank cDNAs indicated that there was no significant contamination by internally primed cDNAs or genomic fragments but that there was a relatively high incidence (12%) of alternative polyadenylation sites. We evaluated the sensitivity and resolution of expression information in BodyMap by in silico Northern hybridization and selection of tissue-specific gene probes. BodyMap is a unique resource for estimation of the absolute abundance of transcripts and selection of gene probes for efficient hybridization-based gene expression profiling.

3' Untranslated Regions↗
PubMed2000

Dimeric inhibin A as a fourth marker for Down's syndrome maternal serum screening in native Japanese women.

OBJECTIVE: This study was conducted to assess the usefulness of dimeric inhibin A as a fourth marker for Down's syndrome screening in addition to AFP, hCG and uE3 markers for native Japanese women. METHODS: Serum specimens from 367 native Japanese women in the second trimester were assayed for dimeric inhibin A levels. Day specific dimeric inhibin A medians were established for gestational ages 15.0-21.9. Weekly median values for the native Japanese were compared with those of a U.S. population. Selected Japanese specimens from 15 diagnosed Down's syndrome and 3 trisomy 18 cases were also assayed for dimeric inhibin A. RESULTS: Dimeric inhibin A levels did not vary greatly over the gestational age range as expected. Median value comparison showed that native Japanese dimeric inhibin A medians are higher than the U.S. population medians by an average of 7.95%. Native Japanese dimeric inhibin A median values in this study are 1.77 times higher in Down's syndrome cases than in unaffected pregnancies. Trisomy 18 dimeric inhibin A levels show no significant difference from the unaffected pregnancies. CONCLUSIONS: This report shows for the first time that dimeric inhibin A can be informative as a fourth marker for Down's syndrome screening in native Japanese women. We expect the addition of dimeric inhibin A to a triple marker protocol will increase the accuracy of predicted risk for all pregnancies screened and increase the detection rate of Down's syndrome affected pregnancies.

Biomarkers↗
PubMed2000

Triple marker screening for trisomy 21, trisomy 18 and open neural tube defects in singleton pregnancies of native Japanese pregnant women.

OBJECTIVE: To report the results of prenatal triple marker screening on a population of Japanese pregnant women. METHODS: From April 1994 through March 1999, a total of 32,925 native Japanese women with singleton pregnancies requested a triple marker-screening test. Multiples of the median values for 3 markers and individual risks for each patient were calculated following adjustment for the Japanese weight correction factor. The risk cut-off values used for Down syndrome (T21), open spina bifida (OSB) and trisomy 18 (T18) were 1: 295, 1: 290, and 1: 100, respectively. Follow-up information was collected postpartum and statistically analyzed. RESULTS: Detection rates (DR) of T21 for women less than 35 years, over 35 years and overall were 58, 94, and 83%, respectively. DR of T18 for women less than 35 years, over 35 years and overall were 75, 79, and 79%, respectively. DR of open neural tube defects (ONTD) was 100%. CONCLUSIONS: The first cumulative data of an intervention program and prospective follow-up studies in Japan have proven to be similar to other published reports. Individual risk values were calculated for each pregnancy for T21, T18 and ONTD. This screening program is more effective than age-dependent screening for detecting T21, T18 and ONTD pregnancies.

Adult↗
PubMed2000

Novel presenilin-1 mutation with widespread cortical amyloid deposition but limited cerebral amyloid angiopathy.

OBJECTIVE: To clarify the phenotypic heterogeneity in deposition of amyloid beta (Abeta) in the parenchyma and in cerebral vessels of the brains of the patients having presenilin-1 (PS1) mutations. Mutations in PS1 induce increased production of Abeta42(43), resulting in an enhanced overall deposition of Abeta protein within the cerebral cortex. METHODS: Sequence analysis of the PS1 gene of DNA from patients with early onset Alzheimer's disease, and immunostaining of brain tissues by end specific monoclonal antibodies against Abeta. RESULTS: Sequence analysis disclosed a novel mutation (N405S) in the PS1 gene in a Japanese patient with early-onset Alzheimer's disease. Postmortem examination of one patient with N405S showed limited cerebral amyloid angiopathy, whereas postmortem examination of another Japanese patient with Alzheimer's disease with the E184D mutation disclosed severe cerebral amyloid angiopathy. The brains of both patients showed widespread neuritic plaques, neurofibrillary tangles, and neuronal loss. Immunostaining showed that Abeta42 was predominant over Abeta40 in neuritic plaques in both patients, whereas Abeta40 was found to be predominant over Abeta42 in cerebral amyloid angiopathy in the patient with E184D. However, most cortical vessels of the patient with N405S were not reactive with either of the antibodies. CONCLUSION: The N405S mutation of PS1 is a major determinant of cortical Abeta deposition but not cerebral amyloid angiopathy in Alzheimer's disease.

Alzheimer Disease↗
PubMed2000

Insufficient secretion of atrial natriuretic peptide at acute phase of myocardial infarction.

To investigate the secretion of the plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction (AMI), we evaluated the relationship between plasma levels of ANP and pulmonary capillary wedge pressure (PCWP) in 45 consecutive patients during the acute phase of AMI ( approximately 12 h after the attack) (group 1) and compared data with those obtained after 1 mo (group 2). In both groups 1 and 2, plasma ANP levels significantly correlated with PCWP. The slope of the linear regression line between the PCWP and ANP in group 1 was significantly lower, by about one-third, than that in group 2. In addition, we examined changes in ANP levels and left ventricular end-diastolic pressure (LVEDP) over 180 min after AMI induced by injection of microspheres into the left coronary arteries of three dogs. The LVEDP and ANP levels 30 min after AMI were significantly higher than those before; however, despite the persistent high LVEDP during the 180 min after AMI, ANP levels decreased gradually and significantly to 63% of the peak level at 150 min. These findings suggest that the secretion of ANP during the acute phase of myocardial infarction may be insufficient relative to the chronic phase.

Acute Disease↗
PubMed2000

Activation of Ca2+-activated K+ channels in human myometrium by nitric oxide.

To investigate the mechanism of human uterine smooth muscle relaxation, the activation of Ca2+-activated K+ channels in cultured myometrial cells obtained from human pregnant myometrium at term by nitric oxide was evaluated at the single cell level using the patch-clamp technique. The open probability of the K+ channel after the addition of 3 x 10(-3) M isosorbide dinitrate, a nitric oxide donor (0.116 +/- 0.048) was significantly higher than that before the addition (0.059 +/- 0.032; n = 9, p < 0.01). In myometrial cells pretreated with lipopolysaccharide, activation of K+ channels was also noted after the addition of L-arginine (10(-4) M; open probability increased from 0.179 +/- 0.076 to 0.380 +/- 0.105, n = 9, p < 0.01: 10(-3) M; open probability increased from 0.073 +/- 0.050 to 0.242 +/- 0.098, n = 12, p < 0.01). Either 10(-3) M N-nitro-L-arginine-methyl-ester, an inhibitor of nitric oxide synthase, or 10(-6) M methylene blue, an inhibitor of guanylate cyclase, abolished activation of the K+ channel by 10(-3) M L-arginine in pretreated myometrial cells with lipopolysaccharide. Application of 10(-3) M L-arginine to the intracellular surface of an excised inside-out patch in the myometrial cells pretreated with lipopolysaccharide failed to increase Ca2+-activated K+ channel activity, suggesting that the activation was mediated by intracellular messengers. These results indicate that nitric oxide should control human myometrial relaxation during pregnancy via activation of Ca2+-activated K+ channels.

Arginine↗
PubMed2000

Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients.

Adiponectin is a novel, adipose-specific protein abundantly present in the circulation, and it has antiatherogenic properties. We analyzed the plasma adiponectin concentrations in age- and body mass index (BMI)-matched nondiabetic and type 2 diabetic subjects with and without coronary artery disease (CAD). Plasma levels of adiponectin in the diabetic subjects without CAD were lower than those in nondiabetic subjects (6.6+/-0.4 versus 7.9+/-0.5 microg/mL in men, 7.6+/-0.7 versus 11.7+/-1.0 microg/mL in women; P<0.001). The plasma adiponectin concentrations of diabetic patients with CAD were lower than those of diabetic patients without CAD (4.0+/-0.4 versus 6.6+/-0.4 microg/mL, P<0.001 in men; 6.3+/-0.8 versus 7.6+/-0. 7 microg/mL in women). In contrast, plasma levels of leptin did not differ between diabetic patients with and without CAD. The presence of microangiopathy did not affect the plasma adiponectin levels in diabetic patients. Significant, univariate, inverse correlations were observed between adiponectin levels and fasting plasma insulin (r=-0.18, P<0.01) and glucose (r=-0.26, P<0.001) levels. In multivariate analysis, plasma insulin did not independently affect the plasma adiponectin levels. BMI, serum triglyceride concentration, and the presence of diabetes or CAD remained significantly related to plasma adiponectin concentrations. Weight reduction significantly elevated plasma adiponectin levels in the diabetic subjects as well as the nondiabetic subjects. These results suggest that the decreased plasma adiponectin concentrations in diabetes may be an indicator of macroangiopathy.

Adiponectin↗
PubMed2000

Effects of cardiac natriuretic peptides on oxidized low-density lipoprotein- and lysophosphatidylcholine-induced human mesangial cell migration.

The objectives of the present study were (1) to determine whether oxidized LDL and lysophosphatidylcholine (lyso-PtdCho), a major phospholipid component of oxidized LDL, stimulate the migration of cultured human mesangial cells and (2) to investigate the possible effects on mesangial cell migration of the cardiac natriuretic peptides atrial and brain natriuretic peptide (ANP and BNP). Oxidized LDL (10 and 100 microg/mL) and lyso-PtdCho (10(-7) to 10(-5) mol/L) stimulated migration in a concentration-dependent manner. In contrast, the effects of native LDL and phosphatidylcholine were modest or nonexistent. Protein kinase C (PKC) inhibitor and downregulation of PKC activity by phorbol ester inhibited oxidized LDL- and lyso-PtdCho-induced migration. Human ANP(1-28) and human BNP-32 significantly inhibited oxidized LDL- and lyso-PtdCho-induced migration in a concentration-dependent manner. C-ANF (des-[Glu(18),Ser(19),Gly(20),Leu(21),Gly(22)]ANP(4-23)), a specific ligand for ANP clearance receptors, could not inhibit oxidized LDL- and lyso-PtdCho-induced migration. Inhibition by ANP and BNP of lyso-PtdCho-induced migration was paralleled by an increase in the cellular level of GMP. Oxidized LDL- and lyso-PtdCho-induced migrations were inhibited by 8-bromo-cGMP. The results suggest that oxidized LDL and lyso-PtdCho stimulate the migration of human mesangial cells, at least in part, through a PKC-dependent process and that ANP and BNP inhibit this stimulated migration, probably through a cGMP-dependent process.

Atrial Natriuretic Factor↗
PubMed2000

Novel polymorphism in the gene region encoding the carboxyl-terminal intracellular domain of the NMDA receptor 2B subunit: analysis of association with schizophrenia.

OBJECTIVE: N-methyl-D-aspartate (NMDA) receptor antagonists are known to produce a syndrome resembling schizophrenia, probably due to their blockade of NMDA receptors. The NMDA receptor 2B (NR2B) subunit has been identified as one of the major proteins in the postsynaptic density at glutamatergic synapses, suggesting that the carboxyl-terminal domain of the NR2B subunit may play a significant role in intracellular signal transduction. METHOD: The authors screened for genetic variations in the region of the NR2B subunit gene encoding the carboxyl-terminal intracellular domain in patients with schizophrenia and studied the association between schizophrenia and a novel polymorphism of the NR2B subunit gene. RESULTS: One silent mutation (2664C/T) was identified. No significant differences in the frequencies of 2664C/T genotypes and alleles were found between patients with schizophrenia and healthy comparison subjects. CONCLUSIONS: The findings provided no evidence of an association between schizophrenia and the 2664C/T polymorphism of the NR2B subunit gene.

Female↗
PubMed2000

Localization of glucokinase-like immunoreactivity in the rat lower brain stem: for possible location of brain glucose-sensing mechanisms.

Pancreatic glucokinase (GK) is considered an important element of the glucose-sensing unit in pancreatic beta-cells. It is possible that the brain uses similar glucose-sensing units, and we employed GK immunohistochemistry and confocal microscopy to examine the anatomical distribution of GK-like immunoreactivities in the rat brain. We found strong GK-like immunoreactivities in the ependymocytes, endothelial cells, and many serotonergic neurons. In the ependymocytes, the GK-like immunoreactivity was located in the cytoplasmic area, but not in the nucleus. The GK-positive ependymocytes were found to have glucose transporter-2 (GLUT2)-like immunoreactivities on the cilia. In addition, the ependymocytes had GLUT1-like immunoreactivity on the cilia and GLUT4-like immunoreactivity densely in the cytoplasmic area and slightly in the plasma membrane. In serotonergic neurons, GK-like immunoreactivity was found in the cytoplasm and their processes. The present results raise the possibility that these GK-like immunopositive cells comprise a part of a vast glucose-sensing mechanism in the brain.

Animals↗
PubMed2000

Central, but not peripheral, glucose-sensing mechanisms mediate glucoprivic suppression of pulsatile luteinizing hormone secretion in the sheep.

Changes in glucose availability are proposed to modulate pulsatile GnRH secretion, and at least two anatomical sites, the liver and hindbrain, may serve as glucose sensors. The present study determined the relative importance of these putative glucose-sensing areas in regulating pulsatile LH secretion in the sheep. Our approach was to administer the antimetabolic glucose analog, 2-deoxy-D-glucose (2DG) into either the hepatic portal vein or the fourth ventricle in gonadectomized females in which LH pulse frequency was high. In the first study, a catheter was placed in the ileocolic vein to determine the effects of local injection of 2DG into the hepatic portal system on the release of LH. After monitoring the pattern of LH secretion for 4 h, 2DG (250 mg/kg) was infused (500 microl/min) into the liver for 2 h. For comparison, animals were also given the same dose of 2DG into a jugular vein for 2 h. Administration of 2DG into either the hepatic portal or jugular vein reduced LH pulse frequency to the same extent. Infusion of the lower dose (50 mg/kg) locally into the hepatic portal vein did not affect plasma LH profiles. Collectively, these results are interpreted to indicate that the liver does not contain special glucose-sensing mechanisms for the glucoprivic suppression of LH pulses. In the second study, 2DG (5 mg/kg) was infused (50 l/min) for 30 min into the fourth ventricle or lateral ventricle. During the subsequent 4-h sampling period, pulsatile LH secretion was significantly suppressed, but there was no significant difference in LH pulse frequency between sites of infusion. Peripheral 2DG concentrations were not detectable after either fourth or lateral ventricle infusions, indicating that the 2DG had acted centrally to suppress LH pulses. Plasma cortisol concentrations increased more in animals infused with 2DG into the fourth ventricle than in those infused into the lateral ventricle, suggesting that 2DG infused into lateral ventricle is transported caudally into the fourth ventricle and acts within the area surrounding the fourth ventricle. Overall, these findings suggest that an important glucose-sensing mechanism is located circumventricularly in the fourth ventricle. Moreover, the liver does not appear to play an important role in detecting glucoprivic action of 2DG to suppress pulsatile LH secretion.

Animals↗
PubMed2000

Synthesis of new synthons for organofluorine compounds from halothane containing sulfur functional groups.

To develop new synthons for the syntheses of organofluorine compounds, the treatment of Halothane, 2-bromo-2-chloro-1,1,1-trifluoroethane, (1) with 4-methylbenzenethiol (2) in the presence of sodium hydride gave 1-chloro-2,2,2-trifluoroethyl 4-methylphenyl sulfide (3), which was oxidized with m-chloroperbenzoic acid (m-CPBA) to the corresponding sulfoxide (4) and sulfone (5). Reaction of 3 and 5 with allyltributyltin in the presence of 2,2'-azobis(isobutyronitrile) (AIBN) gave 1-(trifluoromethyl)-3-butenyl compounds (9, 11). Sulfoxide 4 was decomposed in this condition. The treatment of 3 with allyltrimethylsilane in the presence of Lewis acids gave 1-(trifluoromethyl)-3-butenyl compounds (9) in good yield. This result suggests that 4-methylphenylthio substituent stabilizes the alpha-carbocation effectively, though the trifluoromethyl group destabilizes it strongly. Aromatic compounds similarly reacted with 3 in the presence of titanium(IV) chloride to give 2-aryl-1,1,1-trifluoro-2-(4-methylphenylthio)ethanes. Thus, sulfur compounds derived from Halothane were found to be useful new synthons for organofluorine compounds.

Halothane↗
PubMed2000

Myocardial viability detected by dobutamine echocardiography in patients with chronic coronary artery disease, and long-term outcome after coronary angioplasty.

Viable but dysfunctional myocardium detected by dobutamine echocardiography (DE) predicts early improvement in regional left ventricular (LV) function after percutaneous transluminal coronary angioplasty (PTCA). Whether DE can predict the long-term (>2 years) outcome after PTCA is still unclear. Thus, 50 patients (age 60.4+/-9.5 years) with chronic coronary artery disease and regional LV dysfunction who underwent DE 1 week before PTCA to assess myocardial viability were followed for 4.0+/-0.8 years. Regional LV function and LV ejection fraction (LVEF) were evaluated by 2-dimensional echocardiography in patients who remained event-free (cardiac death or myocardial infarction or unstable angina pectoris) after PTCA. At late follow-up (>2 years after PTCA), 29 patients showed regional LV function improvement, 15 showed no improvement, 3 showed worsening and 3 patients had cardiac events (1 nonfatal myocardial infarction and 2 unstable angina pectoris). LVEF improved (0.53+/-0.09 to 0.60+/-0.09, p<0.001) in patients with improved regional LV function, but deteriorated (0.38+/-0.03 to 0.30+/-0.03) in the 3 patients with worsened regional LV function. Of the 29 patients with improvement, 27 (93%) had viable myocardium, whereas only 3 (20%) of the 15 with no improvement had viable myocardium and all 6 of those with poor outcomes (3 with cardiac events and 3 with worsening) had viable myocardium (chi2 = 28.9, p<0.001). Patients with viable myocardium and a poor outcome had a lower mean LVEF before PTCA, and at 1 week and 3 months after PTCA (p = 0.004, <0.001, and =0.001, respectively), and a higher restenosis rate (p = 0.007) than patients with viable myocardium and without a poor outcome. It is concluded that viable myocardium detected by DE may predict long-term improvement in regional and global LV function after PTCA. However, patients with viable myocardium and persistent low LVEF are at risk for cardiac events or worsening of LV function.

Aged↗