Biomedical subjects

Y Numaguchi

Publications and source records attributed to Y Numaguchi.

At least 19 recordsLinked to original sources

PubMed2001

Involvement of 1,2-diacylglycerol in improvement of heart function by etomoxir in diabetic rats.

Abnormal lipid metabolism has been proposed to be involved in the pathogenesis of diabetic cardiomyopathy. In this study, we measured myocardial lipid levels, including 1,2-diacylglycerol (1,2-DAG) and ceramide (CM), and myocardial function in diabetic rats. We also evaluated the effects of etomoxir (ETM), a carnitine palmitoyl transferase I inhibitor, on diabetic rat hearts from the viewpoints of alterations in lipid second messengers and myocardial function. Rats were injected with streptozotocin (60 mg/kg) to induce diabetes and were treated 5 weeks later with ETM (18 mg/kg) for 8 days. In diabetic rats, heart rate, systolic blood pressure, and fractional shortening were significantly reduced compared with those in controls. Treatment of diabetic rats with ETM ameliorated myocardial dysfunction other than heart rate. Myocardial 1,2-DAG levels in diabetic rats were significantly elevated compared with those in controls, while myocardial CM levels were not. ETM treatment caused an additional increase in myocardial 1,2-DAG levels in diabetic rats, but the CM levels did not change. There was a marked difference in fatty acid pattern of 1,2-DAG between diabetic and ETM-treated diabetic rat hearts. The fatty acids 18:1 and 18:2 were significantly increased and the fatty acids 16:0, 18:0, 20:4, and 22:6 were significantly reduced in ETM-treated diabetic rat hearts. These data suggest 1,2-DAG is involved in ameliorating myocardial dysfunction in diabetic rats and that its source is different between diabetic and ETM-treated diabetic rats. CM is unlikely to be involved in the pathogenesis of diabetic cardiomyopathy or the improvement of cardiac contractility in diabetic rats by ETM.

Animals↗

PubMed2001

Diffusion-weighted echo-planar MR imaging of CNS involvement in systemic lupus erythematosus.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the range of findings at diffusion-weighted magnetic resonance (MR) imaging in patients with systemic lupus erythematosus (SLE) and central nervous system involvement. MATERIALS AND METHODS: Diffusion-weighted MR images were reviewed in 20 patients with SLE and correlated with clinical symptoms and findings at computed tomography, conventional MR imaging, MR angiography, or conventional angiography. RESULTS: Diffusion-weighted MR imaging showed acute or subacute lesions in nine of 20 patients (45%). In the other 11, it showed no abnormal findings or chronic lesions. In four of the nine patients with lesions, diffusion-weighted imaging primarily showed hyperintense lesions with decreased apparent diffusion coefficient (ADC), which indicates acute or subacute infarcts. In four other patients, it primarily showed iso- or slightly hyperintense lesions with increased ADC, suggesting vasogenic edema. In two of these four patients, the findings were consistent with hypertensive encephalopathy. In the other two, small hyperintense foci on diffusion-weighted images with decreased ADC were seen within the vasogenic edema. These foci presumably represent microinfarcts associated with SLE vasculopathy. In the ninth patient, diffusion-weighted imaging showed a small linear hyperintense lesion with normal ADC in the left parietooccipital region. CONCLUSION: Diffusion-weighted imaging shows primarily two patterns of acute or subacute parenchymal lesions in patients with SLE: acute or subacute infarction and vasogenic edema with or without microinfarcts.

Adult↗

PubMed2001

Functional MR imaging of vision in the deaf.

RATIONALE AND OBJECTIVES: Early loss of a sensory modality has been associated with cortical reorganization in both animal models and humans. The purpose of this study was to map visual activation with functional magnetic resonance (MR) imaging and to document possible developmental reorganization in the temporal lobe caused by early deafness. MATERIALS AND METHODS: Six prelingual, profoundly deaf subjects were compared with a similar group of six hearing subjects. Three visual tasks were performed by both groups: attention to movement in the field-of-view periphery, shape matching, and mental rotation. Echo-planar coronal MR imaging was performed at 1.5 T. RESULTS: Regions of interest encompassing the middle and posterior aspects of the superior and middle temporal gyri demonstrated a significantly (P < .05) increased activation in deaf subjects compared with hearing subjects, particularly on the right side (P < .05) and during the tasks involving motion. The most specific effect was noted during the mental-rotation task. CONCLUSION: These results support the hypothesis that portions of the temporal lobe usually involved in auditory processing are more active during certain visual tasks in deaf compared with hearing subjects. Cortical reorganization may be an important factor in the deaf population when considering the physiology of temporal lobe lesions and predicting surgical outcomes. Functional MR imaging may be helpful during preoperative assessment in individuals with deafness.

Adult↗

PubMed2001

Impaired nitric oxide production and enhanced autoregulation of coronary circulation in young spontaneously hypertensive rats at prehypertensive stage.

In the current study, we investigated the NO-generation pathway in response to mechanical stimuli in SHR at the prehypertensive stage. To examine the role of NO in coronary autoregulation, we evaluated the effects of L-NAME on the coronary flow in SHR at both the prehypertensive and hypertensive stages. Isolated perfused hearts from 5- and 15-week-old SHR and from age-matched Wistar-Kyoto rats (WKY) were used. After stabilization at 60 mmHg, perfusion pressure was immediately raised to 90 mmHg to record the change in coronary flow for 10 min without (control) or with NO synthesis blockade by Nomega-nitro-L-arginine methyl ester (L-NAME). NOx- (nitrite/nitrate) was measured in coronary effluent. At 5 weeks of age, SHR did not have hypertension, while the coronary autoregulation was enhanced. L-NAME did not affect this enhanced autoregulation in 5-week-old SHR. At perfusion pressures of both 60 and 90 mmHg, 5-week-old SHR showed less coronary NOx- production than age-matched WKY. At 15 weeks, SHR showed a higher blood pressure than WKY. The coronary autoregulation in SHR remained higher than that in WKY, but was below that in 5-week-old SHR. NOx- production in 15-week-old SHR recovered to the level of age-matched WKY. These results indicate that NOx- production induced by mechanical stimulation was markedly reduced in 5-week-old SHR at the prehypertensive stage, which may have enhanced coronary autoregulation. An impaired nitric oxide production may precede the onset of hypertension in SHR.

Animals↗

PubMed2001

Altered expression of prostacyclin synthase in a subset of the thick ascending limb cells and mesangial cells in 5/6-nephrectomized rats.

The aim of this study was to evaluate the possible role of prostacyclin (PGl2) in the onset and development of hypertension and chronic renal failure in 5/6-nephrectomized rats (5/6NX). We measured the systolic blood pressure, 24-h urinary excretion levels of 6-keto-PGF1alpha, which was a stable metabolite of PGI2, and levels of PGI2 synthase (PCS) mRNA in the kidneys. Immunostaining for PCS in the kidneys was also evaluated. Systolic blood pressure was higher in 5/6NX than in sham-operated rats. The 24-h urinary excretion levels of 6-keto-PGF1alpha in 5/6NX at 1 week postsurgery were lower than in sham-operated rats. In renal morphology, tubulointerstitial injury was observed at 2 weeks postsurgery, and glomerulosclerosis at 4 weeks. Levels of PCS mRNA in 5/6NX decreased significantly at 1 and 2 weeks postsurgery compared with those in sham-operated rats, but at 8 weeks these levels showed a tendency to increase. Immunostaining for PCS was positive in a subset of the cortical thick ascending limb of Henle's loop cells, including macula densa in both groups. Moreover, in 5/6NX at 8 weeks postsurgery, mesangial cells also stained positive for PCS. In conclusion, our findings suggest that PCS might play an important role in mitigating glomerular hemodynamic changes associated with reduction of renal mass.

6-Ketoprostaglandin F1 alpha↗

PubMed2001

Diffusion anisotropy of the internal capsule and the corona radiata in association with stroke and tumors as measured by diffusion-weighted MR imaging.

BACKGROUND AND PURPOSE: Diffusion-weighted MR images have enabled measurement of directionality of diffusion (anisotropy) in white matter. To investigate differences in the anisotropy for various types of pathologic findings and the association between the anisotropy of tracts and neurologic dysfunction, we compared the anisotropy of the posterior limb of the internal capsule and the corona radiata between patients with stroke and those with tumors and between patients with and without hemiparesis. METHODS: Thirty-three patients consisting of 11 with tumors and 22 with ischemic disease (16 acute infarction, four old infarction, and two transient ischemic attack) and nine control patients were studied with a 1.5-T MR imager. Diffusion-weighted images were obtained with diffusion gradients applied in three orthogonal directions. The diffusion anisotropy measurements were obtained from regions of interests defined within the internal capsule and the corona radiata. RESULTS: The diffusion anisotropy was significantly reduced in all internal capsules and coronae radiata involved by infarcts, tumors, and peritumoral edema compared with that of the control patients (P <.0001). This reduction was most prominent in the tracts involved by tumors (P <.05). The anisotropy of the internal capsules and coronae radiata was significantly decreased in cases with moderate-to-severe hemiparesis as compared with those with no or mild hemiparesis (P <.0001). Diffusion anisotropy tended to be also reduced in normal-appearing internal capsules and coronae radiata that were remote from the involved segment of the corticospinal tract. CONCLUSION: The degree of impaired diffusion anisotropy may vary in different pathologic conditions and correlate with neurologic dysfunction. The measurement of diffusion anisotropy may provide additional information relating to neurologic function and transneuronal effects.

Adolescent↗

PubMed2000

Melatonin scavenges hydroxyl radical and protects isolated rat hearts from ischemic reperfusion injury.

During postischemic reperfusion, free radicals are produced and have deleterious effects in isolated rat hearts. We investigated whether melatonin (MEL) reduces the production of hydroxyl radical (*OH) in the effluent and aids in recovery of left ventricular (LV) function. Hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. Salicylic acid (SAL) was used as the probe for *OH, and its derivatives 2,5- and 2,3-dihydroxybenzoic acid (DHBA) were quantified using HPLC. In addition, thiobarbituric acid reactive substances (TBARS) in the myocardium was measured. Plateaus in the measurement of 2,5- and 2,3-DHBA were seen from 3 to 8 min after reperfusion in each group. The group that received 100 microM MEL+ SAL had significantly reduced amounts of 2,5- and 2,3-DHBA by multiple folds, compared to the SAL group. TBARS was significantly decreased in the 100 microM MEL group (1.20+/-0.36 vs 1.85+/-0.10 micromol/g of drug-free group, p<0.001). More importantly, the 100 microM MEL group significantly recovered in LV function (LV developed pressure, +dp/dt, and -dp/dt; 63.0%, 60.3%, and 59.4% in the 100 microM MEL group; 30.2%, 29.7%, and 31.5% in the drug-free group, respectively; p<0.05). Duration of ventricular tachycardia or ventricular fibrillation significantly decreased in the 100 microM MEL group (100 microM MEL, 159+/-67 sec; drug-free, 1244+/-233 sec; p<0.05). As a result of scavenging *OH and reducing the extent of lipid peroxidation, MEL is an effective agent for protection against postischemic reperfusion injury.

Animals↗

PubMed2000

Efficacy of targeted CT angiography in evaluation of intracranial internal carotid artery disease.

RATIONALE AND OBJECTIVES: This study evaluated the efficacy of targeted computed tomographic (CT) angiography in the diagnosis of intracranial internal carotid artery (ICA) disease and compared the results of routine and targeted CT angiography. MATERIALS AND METHODS: Fifty-four patients (24 male and 30 female patients aged 2 months to 87 years) were examined with CT angiography. Digital subtraction angiography (DSA) was performed in 42. CT angiograms were reconstructed with the maximum-intensity projection (MIP) algorithm. Targeted CT angiography was performed by individually reconstructing a single ICA territory. Each ICA was divided into four segments, and findings of routine MIP CT angiography, routine MIP plus targeted CT angiography, and DSA were reviewed independently by two neuroradiologists for vascular lesions involving each segment. Routine and targeted CT angiograms were also evaluated to determine how well both ICAs were visualized. RESULTS: Routine CT angiography was rated good or excellent for ICA visualization in 64% of cases, compared with 81% for targeted CT angiography (P = .0005). The overall agreement between routine CT angiography and DSA and between routine plus targeted CT angiography and DSA was 92% and 94%, respectively. There was no statistically significant difference between the percentages of vascular lesions detected with routine CT angiography alone and with routine plus targeted CT angiography. Both methods tended to show false-positive findings of steno-occlusive disease, but targeted CT angiography showed details of aneurysms and stenotic lesions that were easily overlooked with routine CT angiography alone. CONCLUSION: Routine plus targeted CT angiography, while providing superior image quality, did not have much clinical effect; further assessment may be needed.

Adolescent↗

PubMed2000

Characteristics and pitfalls of contrast-enhanced, T1-weighted magnetization transfer images of the brain.

RATIONALE AND OBJECTIVES: This study was undertaken to clarify the difference in signal pattern on contrast material-enhanced T1-weighted magnetic resonance (MR) magnetization transfer (MT) images between enhancing and nonenhancing lesions in various intracranial diseases and to determine the necessity of nonenhanced MT images for evaluating lesional contrast enhancement. MATERIALS AND METHODS: MR images of 116 patients who underwent nonenhanced T1-weighted imaging, nonenhanced MT imaging, and contrast-enhanced MT imaging were reviewed. The increase in signal intensity of lesions relative to normal brain was compared between nonenhanced T1-weighted images and contrast-enhanced MT images. Signal intensity of lesions was compared with that of the striate nucleus and white matter on contrast-enhanced MT images. True enhancement was determined by comparison with nonenhanced MT images. RESULTS: In all, 143 lesions, including 86 enhancing and 57 nonenhancing lesions, were identified among 63 patients. Almost all (99%) of the enhancing lesions were hyperintense to striate nucleus on contrast-enhanced MT images, and most (>87%) showed moderate to marked signal intensity increase from nonenhanced T1-weighted images to contrast-enhanced MT images. Most (>95%) of the nonenhancing lesions showed mild or no increase in relative signal intensity, and most (75%) were iso- or hypointense to striate nucleus on contrast-enhanced MT images. A few nonenhancing lesions (4%-6%), however, showed increase in signal intensity that was indistinguishable from true enhancement without comparison to non-enhanced MT images. CONCLUSION: Nonenhanced MT images should be obtained to assess pathologic enhancement accurately.

Adolescent↗

PubMed2000

MR volumetric analysis of the human basal ganglia: normative data.

RATIONALE AND OBJECTIVES: The authors undertook this study to identify a precise, semiautomated, reproducible magnetic resonance (MR) imaging technique for measuring the basal ganglia, to establish normative volumetric data, and to verify the presence of previously reported asymmetries. MATERIALS AND METHODS: Twenty-eight healthy adults underwent cranial MR examination. The volumes of the various components of the basal ganglia were measured by means of a combination of thresholding and manual tracing techniques performed with specialized software. The validity of these measurements was assessed by fashioning, imaging, and measuring a practical basal ganglia phantom. Measurement accuracy was also established by means of inter- and intrarater reliability indexes. Normalized volumes were statistically analyzed with analysis of variance and paired t tests. RESULTS: The absolute values of the various components of the basal ganglia varied widely even though the volumes were normalized to differences in intracranial volume. The right caudate nucleus volume was significantly (P < .000001) larger than the left in both men and women and in both right-handed and non-right-handed subjects. This asymmetry led to an increase in the overall volume of the basal ganglia on the right. CONCLUSION: The authors have defined a precise, reproducible technique for measuring various components of the basal ganglia and have established normative data. The basal ganglia, similar to other brain structures, exhibit hemispheric lateralization.

Adult↗

PubMed2000

Ascorbic acid improves postischemic vasodilatation impaired by infusion of soybean oil into canine iliac artery.

This study was conducted to (a) assess postischemic vasodilatation by changes in the vascular cross-sectional area using simultaneous intravascular two-dimensional and Doppler ultrasound before and after the infusion of Intralipid (Pharmacia & Upjohn, Peapack, NJ, U.S.A.); (b) evaluate how antioxidant ascorbic acid modifies the effects of Intralipid on postischemic vasodilatation: and (c) clarify the changes in plasma nitrite and nitrate (NOx-) levels after the infusion of Intralipid with and without ascorbic acid. Twenty-eight mongrel dogs were used to measure for vascular cross-sectional area and average instantaneous peak velocity in the iliac arteries after the 5-min occlusion of the arteries. Postischemic vasodilatation was impaired after the infusion of Intralipid (20%, 2 ml/kg) and this impaired response was reversed by the co-administration of ascorbic acid (30 mg/kg). NG-monomethyl-L-arginine completely abolished postischemic vasodilatation. Plasma NOx levels were significantly reduced after the infusion of Intralipid compared with baseline (11.6+/-0.4 vs. 12.9+/-0.3 microM, p = 0.025) and after infusion of Intralipid with ascorbic acid compared with baseline (11.8+/-0.5 vs. 13.1+/-0.4 microM, p = 0.047). We concluded that ascorbic acid reverses the endothelial dysfunction induced by Intralipid without increasing plasma NOx- levels and that deactivation of nitric oxide by oxidative stress is a primary contributor to Intralipid-induced impaired vasodilation.

Animals↗

PubMed2000

Heschl and superior temporal gyri: low signal intensity of the cortex on T2-weighted MR images of the normal brain.

PURPOSE: To study the normal signal intensity pattern in the primary auditory cortex (first Heschl gyrus [HG]) and the surrounding cortices in the superior temporal gyrus (STG) and middle temporal gyrus (MTG) on T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: Coronal T2-weighted fast spin-echo MR images in 30 neurologically normal patients (60 hemispheres) were retrospectively analyzed. Two raters evaluated the cortical signal intensity of the first HG and the neighboring STG and compared them with those of the MTG and the subcortical white matter. The cortical signal intensities between the first HG and the STG were also directly compared. Coronal MR images, which included images of the anterior and posterior halves of the first HG, were evaluated separately. RESULTS: All first HGs were hypointense to the MTG and were either iso- or hypointense to the STG. Cortical hypointensity was especially prominent in the posterior half; the first HG was isointense to the white matter in 33 (55%) hemispheres. The STG was hypointense to the MTG in 54 (90%) hemispheres and in the anterior halves of 36 (60%) hemispheres. CONCLUSION: These findings demonstrate lower signal intensity of the cortex on T2-weighted images in the first HG and surrounding STG compared with that of the MTG.

Adolescent↗

PubMed2000

Simultaneous intravascular two-dimensional plus Doppler ultrasound is useful for evaluation of postischemic vasodilatation: plasm NOx - levels determined by the Griess method may not reflect the extent of postischemic NO-induced vasodilatation.

Our objective was 1) to assess postischemic vasodilatation using simultaneous intravascular two-dimensional and Doppler ultrasound, and 2) to clarify whether plasma nitrite and nitrate (NOx-) levels change during postischemic vasodilatation. The vascular cross-sectional area (CSA) was evaluated in 18 mongrel dogs, and the average instantaneous peak velocity (APV) in the iliac arteries after the 5-min occlusion of blood flow was determined. Plasma NOx- levels were measured at the baseline, during the occlusion of blood flow, and 1.5, 3, and 10 min after recanalization. The %CSA significantly increased from 30 s to 7 min after the recanalization, and maximal vasodilatation was observed at 1.5 min after the recanalization (14.1 +/- 0.9 to 15.8 +/- 1.0 mm2, p< 0.0001 vs. baseline). Plasma NOx- levels were significantly reduced during the occlusion of blood flow and remained reduced at 1.5, 3, and 10 min after recanalization compared with the baseline values. We concluded that simultaneous intravascular two-dimensional and Doppler ultrasound is useful for assessment during postischemic vasodilatation, and that plasma NOx- levels assayed with the Griess reagent do not significantly increase, even when maximal vasodilatation is observed.

Animals↗

PubMed1999

Prostacyclin synthase gene transfer inhibits neointimal formation in rat balloon-injured arteries without bleeding complications.

OBJECTIVE: This study was designed to compare the effects of prostacyclin synthase (PCS) gene transfer with those of a systemic infusion of beraprost sodium (BPS), a prostacyclin analogue, on vascular smooth muscle cell (VSMC) proliferation and neointimal formation after arterial injury. METHODS: PCS gene (3 or 30 micrograms) was transfected into rat balloon-injured carotid arteries by a non-viral lipotransfection method. BPS (100 or 300 micrograms/kg/day) was subcutaneously infused with osmotic pumps after the injury. LacZ gene (30 micrograms) was used as a control. VSMC proliferation was estimated by the bromodeoxyuridine (BrdU) index (BrdU-positive nuclei/total nuclei) at day 7. Neointimal formation was evaluated at day 14. Each treatment group had six rats. RESULTS: PCS gene transfer prevented the increase in intimal/medial area ratio (3 micrograms: 46.6%, 30 micrograms: 61.1% reduction; P < 0.05, P < 0.01, respectively), as did BPS 300 micrograms/kg/day (49.8% reduction; P < 0.05). BPS 100 micrograms/kg/day, however, had no effects on the ratio. PCS gene transfer and BPS 300 micrograms/kg/day significantly suppressed the BrdU index. BPS 300 micrograms/kg/day group had more frequent hematoma and longer bleeding time. There were no significant differences in blood pressure, heart rate, or urinary volume among all groups. CONCLUSION: Both PCS gene transfer and BPS 300 micrograms/kg/day reduced neointimal formation after arterial injury by inhibiting VSMC proliferation. PCS gene transfer may be a safer therapeutic modality against neointimal formation than a systemic infusion of BPS because the former method resulted in fewer bleeding complications.

Analysis of Variance↗

PubMed1999

Functional MRI study of auditory and visual oddball tasks.

To seek neural sources of endogenous event-related potentials, brain activations related to rare target stimuli detection in auditory and visual oddball tasks were imaged using a high temporal resolution functional MRI technique. There were multiple modality specific and modality non-specific activations. Auditory specific activations were seen in the bilateral transverse temporal gyri and posterior superior temporal planes while visual specific activations were seen in the bilateral occipital lobes and their junctions with the temporal lobes. Modality non-specific activations were seen in multiple areas including the bilateral parietal and temporal association areas, bilateral prefrontal cortex, bilateral premotor areas, bilateral supplementary motor areas and anterior cingulate gyrus. Results were consistent with previous intracranial evoked potential recording studies, and supported the multiple generator theory of the endogenous event-related potentials.

Acoustic Stimulation↗

PubMed1999

Altered gene expression of prostacyclin synthase and prostacyclin receptor in the thoracic aorta of spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to evaluate the possible role of prostacyclin (PGI2) in the pathogenesis of hypertension in spontaneously hypertensive rats (SHR). METHODS: Measurement of mRNA and protein levels of PGH synthase (PGHS)-1, PGI2 synthase and the PGI2 receptor, in the thoracic aorta was performed in SHR aged 5, 10, 20, and 40 weeks old and in age-matched normotensive Wistar-Kyoto (WKY) rats with a competitive polymerase chain reaction method and immunoblotting. Aortic production of 6-keto-PGF1 alpha, the main metabolite of PGI2, was also measured. RESULTS: Compared with age-matched WKY rats, PGHS-1 mRNA and protein levels in the thoracic aorta of SHR increased with age, reaching three- and twofold higher than WKY rats at 40 weeks old, respectively. PGI2 synthase mRNA and protein levels in SHR were significantly higher than in WKY rats at 20 and 40 weeks old. In contrast, PGI2 receptor mRNA levels in SHR were consistently lower than in WKY rats at all ages. CONCLUSIONS: These results provide evidence that hypertension elicits alterations in levels of arachidonic acid metabolites, including PGH2 and PGI2. They also suggest that the decreased expression of PGI2 receptor mRNA in prehypertensive SHR could be one of the causes of hypertension in SHR.

Aging↗

PubMed1999

Relationship between the apolipoprotein E and angiotensin-converting enzyme genotypes and LDL particle size in Japanese subjects.

We investigated whether the apolipoprotein E (apoE) and the angiotensin-converting enzyme (ACE) genotypes contribute to the variance in low-density lipoprotein (LDL) particle size in Japanese subjects (n = 136; M/F= 106/30). ACE polymorphism was associated with neither LDL size nor individual lipid levels. In contrast, the subjects with the epsilon2 allele of the apoE genotype had significantly lower levels of total cholesterol (P = 0.002) and LDL cholesterol (P = 0.004) compared with those without the epsilon2 allele. The subjects with the epsilon4 allele had a significantly smaller LDL particle size than those without the epsilon4 allele (P = 0.012). Separate analyses of the male subjects showed similar associations. A stepwise regression analysis revealed the epsilon4 allele to be an independent contributing variable that could affect LDL particle size. Our results suggest that the apoE genotype is associated with the development of atherosclerotic disease, since the epsilon2 and epsilon4 alleles relate to a decrease in LDL cholesterol levels and a decrease in LDL particle size, respectively.

Adult↗

PubMed1999

Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats.

Carvedilol (CAR) is a vasodilating beta-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg/kg) was administered intraperitoneally, and CAR (30 mg/kg daily) or ATN (150 mg/kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104+/-4 vs. 120+/-4 mmHg, P<0.05) and left ventricular fractional shortening (38.8+/-3.1 vs. 55.4+/-1.3%, P<0.01), and resulted in a significant accumulation of ascites (14.4+/-4.9 vs. 0 ml, P<0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4+/-7.1 vs. 51.5+/-1.2 nmol/g heart, p<0.01). CAR prevented the increase in TBARS content (48.8+/-3.0 nmol/g heart, P<0.01 vs. DOX group), whereas ATN had no significant effect (74.3+/-5.2 nmol/g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its beta-blocking property.

Animals↗