Atherosclerosis and angiogenesis. Its pathophysiological significance in humans as well as in an animal model induced by the gene transfer of vascular endothelial growth factor.
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Animals↗
Biomedical subjects
Y Nakashima
Publications and source records attributed to Y Nakashima.
Wild-type p53 gene transfer: a novel therapeutic strategy for neointimal hyperplasia after arterial injury.
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Animals↗
Purification of deoxyribonuclease I using two-step chromatography.
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Animals↗
Effect of aortic valve replacement on coronary flow velocity during metabolic stress in a patient with aortic stenosis.
The effect of aortic valve replacement on coronary flow velocity during atrial pacing and papaverine-induced-resistance vessel dilatation was tested in a patient with aortic stenosis. Although systolic flow reversal disappeared early after the valve replacement, rapid atrial pacing caused myocardial ischemia with lactate production. The coronary flow reserve also remained depressed. These results suggest that the alteration in the coronary flow profile early after the aortic valve replacement does not reflect an improvement in the flow increase during metabolic stress in a patient with aortic stenosis.
Aortic Valve↗
Comparative effects of dobutamine and amrinone on coronary blood flow in patients with idiopathic dilated cardiomyopathy.
Although amrinone has favorable hemodynamic effects in patients with congestive heart failure, little is known about its effects on coronary blood flow (CBF). We compared the effects of intravenous low-dose dobutamine and amrinone on CBF in 10 patients with dilated cardiomyopathy using a Doppler guidewire. We infused dobutamine at a dose of 5 and 10 microg/kg/min for 5 min. After the end of each stage, coronary flow velocity (CFV) and coronary arterial diameter (CAD) in the proximal left anterior descending coronary artery, and hemodynamic variables were obtained. After the CFV and hemodynamics returned to baseline, we infused 1 mg/kg of amrinone over 5 min, and obtained these variables at 5 and 10 min after the cessation of the infusion. CAD did not increase with dobutamine, but significantly increased after amrinone (% increase: 10 +/- 7%; P < 0.001 vs. baseline). CFV progressively increased with dobutamine (5 microg/kg/min: 21 +/- 26%; P < 0.05 vs. baseline; 10 microg/kg/min: 53 +/- 42%; P < 0.005 vs. baseline and 5 microg/kg/min), but slightly decreased after amrinone (-4 +/- 17%; P = not significant vs. baseline). CBF increased during dobutamine (5 microg/kg/min: 25 +/- 29%; P < 0.05; 10 microg/kg/min: 66 +/- 55%; P < 0.005) and after amrinone (19 +/- 22%; P < 0.05) compared to that at baseline. Although there was a significant correlation between the percent increase in CFV and that in dP/dt during dobutamine infusion (r = 0.82, P < 0.001), this correlation was not observed after amrinone (r = 0.23). In conclusion, although both agents significantly increased CBF in patients with dilated cardiomyopathy, they do so by different mechanisms. Amrinone mainly increases CBF by causing dilatation of epicardial coronary arteries. These results suggest that amrinone has beneficial effects on coronary flow dynamics in dilated cardiomyopathy.
Adult↗
Acute myocardial infarction in a patient during dobutamine stress echocardiography.
We report the case of a patient who developed an acute anteroseptal and inferior myocardial infarction during dobutamine stress echocardiography. The proposed mechanism for this event is discussed based on results obtained during emergency coronary angioplasty and subsequent clinical findings.
Angioplasty, Balloon, Coronary↗
Measurement of myocardial fractional flow reserve during coronary angioplasty in patients with old myocardial infarction.
Although myocardial fractional flow reserve (FFRmyo) has been demonstrated to be a useful index for determining functional significance of coronary stenosis, the data in previous studies was derived from a highly selected group of patients. The aim of this study was to investigate the value of FFRmyo in a more clinically relevant group of patients, especially in patients who also had resistance vessel dysfunction. We measured FFRmyo in 20 consecutive patients who had undergone elective coronary angioplasty. FFRmyo was calculated by the ratio of Pc/Pa during intracoronary adenosine 5'-triphosphate (ATP; 50 micrograms in the left coronary and 20 micrograms in the right coronary artery) induced maximal hyperemia, where Pa represents mean aortic pressure obtained by the guiding catheter and Pc represents mean distal coronary pressure measured by a 2.1 F infusion catheter. In total, 21 vessels were dilated and 14 of them were infarct-related arteries. The percent diameter stenosis significantly decreased from 80 +/- 14% to 27 +/- 17%, and the FFRmyo increased significantly from 0.46 +/- 0.18 to 0.77 +/- 0.15 after angioplasty. There was no significant differences in the FFRmyo between vessels with previous myocardial infarction and those without, after angioplasty (0.78 +/- 0.18 vs. 0.76 +/- 0.08). There was a significant correlation between the percent diameter stenosis and FFRmyo before (r = 0.83, P < 0.001) and after (r = 0.64, P < 0.01) angioplasty. In conclusion, FFRmyo significantly improved immediately after angioplasty in vessels with myocardial infarction as well as those without. These results led us to suggest the usefulness of FFRmyo in patients who had both epicardial stenosis and resistance vessel dysfunction. The significant correlation between FFRmyo and quantitative coronary arterial diameter stenosis would further support the more widespread use of FFRmyo in the clinical setting.
Adult↗
Plasma nitrite/nitrate level is inversely correlated with plasma low-density lipoprotein cholesterol level.
BACKGROUND: Plasma nitrite/nitrate (NOx) is a stable end product of the vasodilator nitric oxide (NO). However, there are few reports about plasma NOx levels in humans. HYPOTHESIS: The purpose of this study was to assess the availability of plasma NOx for evaluating basal endogenously-synthesized or endothelium-derived NO, and to examine whether NOx levels are lowered in patients with coronary artery disease (CAD) or its risk factors. METHODS: Plasma NOx levels were measured using an automated system based on the Griess reaction. NOx levels for a 24-h period reproducibly became lowest at 6 A.M. in restricted healthy volunteers, and became stable in inpatient volunteers at 6 A.M. within 4 days after admission. RESULTS: Based on these findings, NOx levels at 6 A.M. in inpatients can be considered as the basal levels. In 40 inpatients suspected of CAD (28 men, 12 women; mean age 60 +/- 11 years), the basal levels of NOx were not related to CAD and its risk factors, except for hypercholesterolemia. The NOx level of patients with hypercholesterolemia was significantly lower than that of patients with normal cholesterol (n = 16,34 +/- 16 mumol/l vs. n = 24, 49 +/- 23 mumol/l, p < 0.03). Furthermore, the NOx levels correlated negatively with the total cholesterol and low-density lipoprotein cholesterol levels (r = -0.40, p < 0.01; r = -0.47, p < 0.003, respectively), but not with other lipid fraction levels. CONCLUSION: The results suggest that the quantity of basal endothelium-derived NO synthesis may be decreased in the presence of hypercholesterolemia.
Case-Control Studies↗
Cervical spinal cord compression in hereditary multiple exostoses. Report of a case and a review of the literature.
Spinal cord compression is an extremely serious complication of hereditary multiple exostoses (HME). A case of HME with compression of the cervical spinal cord is reported. Complete recovery following surgery was achieved. A review of the relevant literature revealed 51 previous cases of HME with cord/cauda equina compression. Most patients were under 30 years of age with more men affected than women. The family history was positive in 60%. The cervical and thoracic areas were predominantly affected, with the symptoms usually developing slowly. Recovery following surgery is to be expected in the majority of cases. In patients with HME and suffering from neurological symptoms, the possibility of spinal cord compression should be considered. Prompt diagnosis and surgical excision provide the best prognosis.
Adolescent↗
Role of K+ channels in EDHF-dependent relaxation induced by acetylcholine in canine coronary artery.
To identify the K+ channels responsible for endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation, we studied the effects of various K+ channel blockers on acetylcholine-induced relaxation, which persists even in the presence of both an inhibitor of nitric oxide synthase and that of cyclooxygenase, in canine coronary artery rings. A nonselective K+ channel blocker, tetrabutylammonium (TBA), a large and intermediate conductance Ca2+-activated K+ channel blocker, charybdotoxin (CTX), and a voltage-dependent K+ channel blocker, 4-aminopyridine (4-AP), significantly inhibited this residual relaxation. A combined treatment with CTX and 4-AP almost completely blocked the relaxation. Neither a large (iberiotoxin) nor a small (apamin) conductance Ca2+-activated K+ channel blocker blocked the relaxation. We also investigated effects of K+ channel blockers on basal tone to determine whether or not EDHF is involved in regulating basal tone. TBA and CTX substantially raised basal tone to a greater degree in endothelium-intact preparations than in endothelium-denuded preparations. These results indicate that EDHF may exert its relaxing action through intermediate conductance Ca2+-activated and voltage-dependent K+ channels in canine coronary arteries. In addition, EDHF may play a role in maintaining basal vascular tone.
4-Aminopyridine↗
Scintigraphic evaluation along with CT and MR images in a case of huge gravitation abscess.
The authors presented a rare case of huge gravitation abscess. 67Ga scintigraphy was useful in the evaluation of the extent and activity of the disease. CT showed clearly the location and shape of the abscess. Enhanced MRI showed vertebral lesions as characteristic geographic and ring-like enhancement.
Abscess↗
A PET-study of [11C]FLB 457 binding to extrastriatal D2-dopamine receptors in healthy subjects and antipsychotic drug-treated patients.
We recently developed [11C]FLB 457 a substituted benzamide with the very high affinity of 20 pM for D2-dopamine receptors in vitro. The aim of the present exploratory study was to examine the anatomical distribution of [11C]FLB 457 binding in the human brain and to determine extrastriatal D2-receptor occupancy in antipsychotic drug-treated patients. [11C]raclopride was used to obtain reference values for D2-dopamine receptor occupancy in the putamen. After IV injection of [11C]FLB 457 there was a high concentration of radioactivity, not only in the caudate putamen but also in the thalamus and the temporal cortex. The concentration of radioactivity in the frontal cortex, the substantia nigra and the colliculi was slightly higher than in the cerebellum. Pretreatment with haloperidol and fluphenazine indicated that [11C]FLB 457 binding in extrastriatal regions to a high degree represent specific binding to D2-dopamine receptors. The D2-occupancy in antipsychotic drug-treated patients was on the same level in the thalamus and the temporal cortex as that determined with [11C]raclopride in the putamen. The study shows that [11C]FLB 457 has potential for quantitative PET-examination of D2-dopamine receptors in man.
Adult↗
Effects of lidocaine and diltiazem on recovery of electrophysiologic activity during partial reperfusion following severe myocardial ischemia in canine hearts.
The effects of lidocaine and diltiazem on recovery of electrophysiologic activity during partial reperfusion following severe myocardial ischemia were investigated in 28 dogs. The left anterior descending artery was ligated, and the distal end was connected to the carotid artery. Myocardial ischemia was induced by retrograde blood flow for 10 minutes, after which flow-limited reperfusion (30-60% of the coronary flow before ischemia) was performed. The dogs were divided according to the agent administered before ischemia into the following three groups: saline (group S, n = 11); lidocaine (group L, n = 8, 0.07 mg/kg/min by intravenous drip infusion following 2 mg/kg intravenous injection); and diltiazem (group D, n = 9, 0.02 mg/kg/min by intravenous drip infusion. There were no significant differences among the three groups in the incidence of ventricular tachyarrhythmia, which occurred as ventricular tachycardia (VT) or ventricular fibrillation (VF). In each group, the occurrence of VT was frequently preceded by delayed potential which was initiated after reperfusion, with depressed conduction in the epicardium, suggesting reentry (82%, 96%, and 87%, not significant). The determining factors for VT with degeneration into VF were long duration of VT in groups S and L (VT with degeneration into VF vs VT without, 1.2 +/- 0.2 seconds vs 0.6 +/- 0.1 seconds, P < .05, in group S and 11.6 +/- 2.5 seconds vs 2.2 +/- 0.4 seconds, P < .05, in group L), and decrease in average R-R interval during VT in groups L and D (195 +/- 8 ms vs 313 +/- 17 ms, P< .01, in group L and 201 +/- 11 ms vs 327 +/- 28 ms, P< 0.01, in group D). In addition, occurrence of epicardial electrophysiologic activity with reduced time from onset of the QRS complex in the surface electrocardiogram to the onset of the activity during VT preceded VF in group L (VT with degeneration into VF vs VT without, 130.0 +/- 15.1 ms vs 185.8 +/- 21.4 ms, P < .05), while that with prolongation of the time had this effect in group D (116.0 +/- 15.7 ms vs 69.0 +/- 10.7 ms, P < .05). It is concluded that, even when partial reperfusion is applied, neither lidocaine nor diltiazem suppresses VT because neither drug decreases delayed potential acting as a triggering factor or suppresses VF, since the alteration of the epicardial conductivity during VT can change the VT circuit to a smaller one.
Animals↗
Implication of the negative U wave during dobutamine stress echocardiography.
Although the development of negative U waves during exercise is a highly specific marker for detecting coronary artery disease, their assessment during exercise is difficult. The clinical significance of the negative U wave during dobutamine stress echocardiography was investigated in 181 patients who had suspected coronary artery disease. Dobutamine-induced negative U waves appeared in 28 patients (16%) during dobutamine infusion. Coronary angiography showed coronary artery disease in 114 of the 181 patients. The sensitivity and specificity of the negative U wave for detecting coronary artery disease were 22 and 96%, respectively, while the corresponding values for ischemic ST-T changes were 49 and 76%, respectively. The negative U wave appeared during low-dose infusion of dobutamine (5-10 microg/kg/min) in 82% of the patients with this wave. In the 21 patients who had both a negative U wave and an inducible regional wall motion abnormality during dobutamine infusion, the development of the negative U wave was either simultaneous with or earlier than that of the wall motion abnormality. Although its sensitivity was low, the negative U wave during dobutamine stress echocardiography is a highly specific marker for detecting coronary artery disease. Because of its earlier appearance as compared with that of the wall motion abnormality, the dobutamine-induced negative U wave may be considered to be an early and useful adjunctive sign for detecting coronary artery disease during dobutamine stress echocardiography.
Adult↗
Pharmacokinetic study of aniracetam in elderly patients with cerebrovascular disease.
The clinical pharmacokinetics of the cognitive enhancer, aniracetam (200 mg), was studied in elderly patients with cerebrovascular disease (CVD) and compared with those of young healthy volunteers. Six female hospitalized patients (mean age 84.5 years) were used in this study. The serum level of anisic acid and p-methoxyhippuric acid, major metabolites of aniracetam, reached a peak at 2 h after oral administration, and returned to basal level by 6 h. Mean creatinine clearance was 20-30 ml/min. The t1/2 of metabolites was increased by 4- to 7-fold in the elderly patients compared with young volunteers. This study showed that tmax, t1/2, and AUC were enlarged in the elderly; however, no clinical side effects were observed.
Adult↗
Mouse deoxyribonuclease I (DNase I): biochemical and immunological characterization, cDNA structure and tissue distribution.
Mouse urinary deoxyribonuclease I (DNase I) resembles rat and human DNase Is in terms of its proteochemical and enzymological properties. Furthermore, mouse DNase I was demonstrated to be immunologically closer to the rat than to the human enzyme. A 1176 bp full length cDNA encoding mouse DNase I was constructed from RNA obtained from the kidney and parotid glands. The amino acid sequence up to the 45th residue from the N-terminal of the mature enzyme was identical to that deduced from the cDNA sequence. This DNase I was distributed most densely in the parotid glands from the standpoint of both enzyme activity and gene transcript levels.
Amino Acid Sequence↗
Hexachlorobenzene accumulated by dams during pregnancy is transferred to suckling rats during early lactation.
The distribution of ingested stable, lipophilic environmental pollutants in dams and their transfer to fetuses and sucklings were investigated in rats fed a diet containing a small amount (35.1 nmol/100 g diet) of hexachlorobenzene (HCB). In the first experiment, we examined the distribution of HCB in pregnant and nursing rats fed the HCB diet during pregnancy and lactation. Its transfer to their sucklings was also studied. On d 16 after parturition, HCB concentrations in the blood, and subcutaneous and perirenal fat of nursing rats fed the HCB diet during pregnancy and lactation were approximately 1/3.5, 1/15 and 1/2.8, respectively, those of pregnant rats fed the HCB diet only during pregnancy. On the other hand, the HCB concentrations in the blood, and subcutaneous and perirenal fat of sucklings were approximately 6, 29 and 15 times higher than those of their dams. Therefore, a large amount of HCB apparently was transferred from dams to suckling pups through the milk. In the second experiment, we fed dams the HCB diet only during pregnancy and determined the distribution of HCB in the pregnant rats and fetuses as well as in the nursing rats and suckling pups. The estimated amount of HCB transferred from a dam to her fetuses corresponded to about 0.39% of her total intake during pregnancy. The amount of HCB detected in nursing rats on d 16 after parturition was much smaller than that in the pregnant rats, suggesting that a large proportion of the HCB that accumulated during pregnancy disappeared from the organs and fat tissues during lactation. The HCB concentration in the stomach contents of suckling pups fed by the dams who had consumed HCB before parturition was highest on d 2 after birth and decreased gradually during the 16 d after birth. In the blood, liver and fat tissues of suckling rats, the HCB concentrations increased until 7 d after birth and then decreased gradually. We conclude that the HCB that accumulated in dams during pregnancy was transferred to their suckling pups through milk in the early days after birth.
Animals↗
Radiofrequency catheter ablation of an accessory pathway in dextrocardia.
A 60-year-old woman with situs inversus and paroxysmal supraventricular tachycardias utilizing an AV accessory pathway underwent successful, uncomplicated RF ablation. Using biplane fluoroscopy, accessory pathway catheter ablation in dextrocardia is as safe, easy, and useful as that for normal heart structure cases, and does not require a lengthy procedure.
Catheter Ablation↗