[Arrhythmia and sudden cardiac death].
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Biomedical subjects
Publications and source records attributed to I Yamaguchi.
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Intra-arterial infusion chemotherapy through a catheter incubated at the recurrent radial artery and connected to an implantable reservoir was performed in eight patients with supraclavicular lymph node metastasis including four locally advanced recurrent breast cancers and two inflammatory breast cancer. Clinical response in breast cancer patients was 1 CR, 3 PR, 1 NC, and 1 PD. There was no complication related with catheter insertion. Therefore from the aspect of quality of life, this system was considered useful for treatment of advanced breast cancer, especially locally advanced recurrent breast cancer.
In order to examine the aging effects on blood biochemical parameters, 25 aged females (70 +/- 8 years old at the beginning of this investigation) were studied prospectively for 7 years. Biochemical parameters were measured in 1982, 1985, 1987, and 1989. Component scores were obtained by principal component analysis applied to all of these 100 data. The data of 13 biochemical parameters and 4 component scores were analyzed for aging, cohort, and time effects by utilizing 3 types of approach i.e., longitudinal, cross-sectional, and time-series. Positive aging effects were observed on blood urea nitrogen and 4th component score. Fourth component score had positive relations to blood urea nitrogen and total bilirubin, and a negative relation to total protein. This 4th component score increased with longitudinal age changes among all cohorts divided by decade, and it increased markedly over 70 years old. These results suggest that the aging effects on biochemical parameters are related with both the decrease in glomerular and hepatocellular functions and the increase in breakdown of tissue protein.
Penile erection was studied in rats injected with pilocarpine, amantadine and apomorphine. Pilocarpine and apomorphine are direct stimulants of muscarinic and dopaminergic receptors, respectively, while amantadine is reported to be an indirect stimulant of dopaminergic nerves. Single intraperitoneal injection of pilocarpine (0.1-3.2 mg/kg), amantadine (1-32 mg/kg) and apomorphine (0.01-1 mg/kg) increased the number of penile erections with bell-shaped dose-response curves. The penile erections, irrespective of the stimulant used, were antagonized by doses (0.032-1 mg/kg) of scopolamine but not by those of methylscopolamine. Sulpiride treatment (1-32 mg/kg) had little effect on pilocarpine-induced penile erection while it attenuated dose-dependently the apomorphine- and amantadine-induced ones. Medial septum and fimbria-fornix lesions abolished penile erections by amantadine and apomorphine but not by pilocarpine. The similar results with amantadine and apomorphine suggest that the drugs activate postsynaptic dopamine receptors, which indirectly activate the septohippocampal cholinergic pathway to induce penile erections. Possible linkage between dopaminergic and cholinergic nerves is discussed.
Seventeen patients with a previous myocardial infarction were studied during pacing to characterize the clinical correlates of ST elevation, to analyze the relation between ST elevation and negative T-wave normalization and to investigate the mechanism of these electrocardiographic changes. Myocardial ischemia was evaluated by measurement of blood lactate, and wall motion was analyzed using cardiokymographs concurrently and serially. Results show that ST elevation and negative T-wave normalization were most marked in leads containing abnormal Q waves, that ST elevation greater than or equal to 1 mm during pacing was associated with a significant increase in left ventricular end-diastolic pressure and deterioration of left ventricular wall motion and that the magnitude of ST elevation and negative T-wave normalization was significantly correlated, but the latter appeared earlier and more markedly. In addition, there was no significant correlation between the extent of either ST elevation or negative T-wave normalization and myocardial lactate production. Thus, ST elevation and negative T-wave normalization are caused by abnormal left ventricular wall motion rather than myocardial ischemia. Negative T-wave normalization is a more sensitive marker of abnormal wall motion than ST elevation in patients with a previous myocardial infarction.
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Blasticidin S (BS), a fungicide of microbial origin, is used for the practical control of rice blast disease. It has broad antimicrobial activity but occasionally exhibits adverse phytotoxic effects on some dicot plants. An inactivating enzyme, BS deaminase, was discovered in the BS resistant strain, Bacillus cereus K55-S1, and the structural gene, bsr, for the enzyme has been cloned. We introduced the bsr gene into tobacco plants using the Ti plasmid vector system and demonstrated that the bsr gene conferred a BS resistant phenotype to the plants. Thus the bsr gene could be useful as a selective marker for plant transformation and provides an example for a new approach to the solution of phytotoxicity problems associated with the use of some types of fungicide.
The authors conducted this study to find the difference in body surface isopotential maps in 46 patients with previous anterior infarction with and without septal involvement. Thallium-201 myocardial-perfusion imaging identified 25 patients with septal infarction (group P) and 21 without (group N). In contrast to group N, group P had a prominent minimum on the anterior chest during the early phases of the QRS. According to the results obtained, the following criteria for identifying patients with septal infarction (group P) were proposed (1). Criterion 1: The absolute value of the voltage of the minimum is equal to or greater than that of the maximum at 5 ms after the onset of the QRS; (2) Criterion 2: During the early portion of the QRS the voltage of the minimum reaches -0.10 mV at the same time or earlier than the maximum reaches 0.10 mV. Both criteria had higher sensitivities (100% and 100%), specificities (71.4% and 90.5%), and predictive accuracies (87.0% and 95.7%) than either Franklead vectorcardiograms or standard 12-lead electrocardiograms in the study population. Thus, body surface isopotential mapping is considered to be useful for the diagnosis of septal involvement in patients with previous anterior myocardial infarction.
The blasticidin S resistance gene (bsr), originally isolated from Bacillus cereus, was studied in Bacillus subtilis. It was found that a 617 bp fragment including the intact bsr gene and its 5' flanking region could confer BS resistance on B. subtilis when integrated in its chromosome, even in a single copy state. The construction of a bsr gene cassette and its practical application as a novel selection marker for B. subtilis are reported.
The effect of TA-870, a novel dopamine prodrug, on the cardiovascular system was studied in anesthetized open- and closed-chest dogs. Intraduodenal administration of less than or equal to 12 mg/kg TA-870 to anesthetized dogs increased left ventricular (LV) dP/dtmax and dP/dt/Pmax. Furthermore, at a lower dose of TA-870 (2 mg/kg), renal vascular resistance (RVR) decreased and renal blood flow (RBF) increased. Similarly, total peripheral resistance (TPR) decreased and cardiac output (CO) increased at less than 4 mg/kg. In an intravenous cumulative dose-response study of TA-870, the plasma-free-dopamine concentration was elevated depending on the dose of TA-870. Renal vasodilation occurred at a low plasma-free-dopamine concentration, whereas a positive inotropic action required higher plasma-free-dopamine. However, the dose-response curve for LVdP/dt/Pmax was steeper than that for RBF or CO. Heart rate was less affected than LVdP/dt/Pmax in open-chest dogs and decreased in closed-chest dogs. Propranolol strongly inhibited the effect of TA-870 on LVdP/dt/Pmax. It also inhibited the effects of TA-870 on TPR and CO to a lesser extent, and the remaining effects were almost completely inhibited by an additional treatment with the dopamine blocker, RS-sulpiride. In conclusion, TA-870 increased myocardial contractility and output by the enteral route, and the latter effect was produced at lower doses with the help of peripheral vasodilation due to the activation of dopamine receptors.
Subcutaneous administration of Z-100 twice a week starting immediately after supralethal whole-body irradiation of mice produced a prolongation of survival time. The effect of Z-100 on the hematopoietic system was thought to have contributed to the prolongation and was thus investigated. A single subcutaneous dose of Z-100 immediately after irradiation inhibited reduction of the total number of nucleated cells in the femoral bone marrow of the treated mice, although the inhibition was not by promotion of the proliferation of specific cells but by promotion of the recovery of multiple cell lines. Treatment with Z-100 promoted colony formation in the spleen of the treated mice and CFU-S formation in the femoral bone marrow, indicating that the drug accelerated the recovery of hematopoietic stem cells. The recovery of CFU-C count was also promoted by Z-100, which suggested that the drug has a restoring effect on the recovery of granulocytic and macrophagic precursor cells. Furthermore, Z-100 produced a greater increase in the CSF activity in the serum of irradiated mice, leading to the presumption that CSF induced by Z-100 was greatly involved in promoting the recovery of the above-mentioned hematopoietic stem cells. We conclude that Z-100 prolonged survival time of irradiated mice by promoting recovery of hematopoiesis of the mice.
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The localization of creatine kinase M (CK-M) in both normal and acute ischemic canine myocardial cells was studied by immunoelectron microscopy using the anti-CK-M Fab'-horseradish peroxidase conjugate. Myocardial ischemia was induced by occlusion of the left anterior descending coronary artery for 15, 60, or 180 minutes. In the normal myocardial cells, CK-M was localized mostly in the A-band and some in the Z-line, M-line, sarcolemmal membrane, and membrane of sarcoplasmic reticulum. Most CK-M in the A-band appeared to associate with thick fibers. This finding strongly suggests that the CK associated with thick fibers may be the enzyme to rephosphorylate ADP produced by myosin ATPase. In 15 minutes of myocardial ischemia, CK-M showed only minimal changes in its location, i.e., almost similar to normal, indicating that the CK in the A-band still has the ability to couple with myosin ATPase. However, in 60 and 180 minutes of ischemia, the A-band CK dissociated markedly from thick fibers, diffused to the I-band and leaked out to the intercellular spaces. These results suggest that the dissociation and disappearance of the A-band CK from thick fibers induced by progress of myocardial ischemia disrupt the myocardial energy transport system via CK reaction, and lead to the irreversible injury of myocardial cells.
Intraduodenal administration of N-(N-acetyl-L-methionyl)-O, O-bis(ethoxycarbonyl)dopamine (TA-870), a newly synthesized dopamine derivative, increased the renal blood flow (RBF) and mesenteric blood flow in anesthetized dogs, while blood pressure and heart rate were less affected. It also increased the glomerular filtration rate, urine volume, and urinary sodium excretion in saline-loaded anesthetized dogs. In conscious dogs, TA-870 and dopamine hydrochloride (DA-HCl) increased RBF in parallel with increases in plasma free dopamine (free-DA) concentration. At an equimolar dose of 71 mumols/kg, p.o., the effect of TA-870 continued for greater than 4 h, while that of DA-HCl lasted for only 2 h: the peak free-DA concentration and maximum increase in RBF were 155 +/- 57 ng/ml and 56 +/- 15%, respectively, for TA-870, and those for DA-HCl were 32 +/- 13 ng/ml and 36 +/- 10%. Similarly, TA-870 showed greater increases in both RBF and plasma free-DA concentration than DA-HCl in anesthetized rats. In contrast to enteral administration, intravenously administered TA-870 exhibited weaker effects than intravenous DA-HCl in anesthetized dogs. In conclusion, TA-870 is an orally effective dopamine prodrug capable of producing higher and more sustained plasma concentrations of dopamine than DA-HCl when administered by the enteral route.
The mechanism of action of a new orally active dopamine (DA) prodrug, TA-870 (N-(N-acetyl-L-methionyl)-O,O-bis(ethoxycarbonyl)(DA) was studied. When TA-870 (1 mg/kg) was injected in anesthetized dogs, renal vascular resistance was decreased and renal blood flow was increased. The renal vasodilatory effect of TA-870 correlated with the plasma level of DA but not with the level of de-ethoxycarbonyl metabolite of TA-870 (i.e., N-(N-acetyl-L-methionyl)DA; DEC-TA-870). The renal vasodilatory effect of TA-870 was inhibited strongly by haloperidol and slightly by propranolol. Pretreatment with phenoxybenzamine enhanced the renal vasodilatory effect of TA-870. In the isolated rabbit splenic artery, TA-870 and DEC-TA-870 showed no effects, whereas dopamine showed a contracting effect, which was inhibited by phentolamine. In the propranolol- and phentolamine-treated splenic artery, TA-870 and DEC-TA-870 caused weak relaxant effects on PGF2 alpha-induced contraction. These effects were not antagonized by metoclopramide. On the other hand, DA showed a strong relaxant effect, which was competitively inhibited by metoclopramide. In addition, TA-870 and DEC-TA-870 further relaxed the artery that had been maximally relaxed by DA. We concluded that TA-870 and DEC-TA-870 exert weak vasodilatory effects that are different from that of DA in vitro, and that TA-870 exerts its vasodilatory effect after its conversion to free DA in vivo.
Cardiovascular response to supine exercise was studied in 11 patients with chronic ventricular pacing for complete atrioventricular block whose heart rate was fixed during exercise, and compared with 11 age- and sex-matched normal subjects. Oxygen uptake increased linearly with increasing work rate, and attained maximum values of 15.7 +/- 0.7 and 29.5 +/- 1.1 ml/min.kg, respectively. In both groups, cardiac output increased in association with oxygen uptake, although the maximum value in the patients was less than one half that in the controls (6.8 +/- 0.5 and 15.1 +/- 0.3 l/min). Stroke volume, however, could change in patients, as in the controls under similarly increased afterloads (maximum values were 96 +/- 7 and 93 +/- 3 ml/beat, respectively). During exercise, the systolic arterial pressure elevated to a similar extent in both groups (221 +/- 14 and 235 +/- 12 mmHg, respectively). The increase in stroke volume in the patients was achieved by complete systolic emptying and the Frank-Starling mechanism. It is considered that in patients with ventricular pacing, exercise can produce an increase in stroke volume when myocardial function is not impaired.
To study the age-related changes of the sinus node function and the variations of influence of autonomic nervous system, pharmacologic total autonomic blockade (TAB) was conducted in 35 patients with symptomatic sinus bradycardia (21 men and 14 women, 50 +/- 21 years, mean +/- SD). Twenty-one patients [Group I, consisting of 14 patients younger than 60 years (group IY) nd 7 patients 60 years or older (group IE)] had a normal intrinsic heart rate (IHRo), and 14 patients had an abnormal IHRo [Group II, consisting of 8 patients younger than 60 years (group IIY) and 5 patients 60 years or older (group IIE)]. The basic cycle length was significantly longer in group II than in group I, suggesting that intrinsic sinus node function was more seriously deteriorated in group II in spite of the compensatory effect of autonomic regulation. In group II it was characteristic that the cycle length (CL) after atropine sulfate administration was longer than the CL of the predicted intrinsic heart rate (IHRp). Otherwise, some group II patients might be regarded as normal by atropine sulfate administration alone. Parasympathetic tone showed a negative correlation with age, and it was most enhanced in group IIY, suggesting that parasympathetic negative chronotropy was stronger in this group. In the course of propranolol administration, prolongation of CL was significantly larger in group IIE than in group IIY, but there was no age-related difference in group I. In group II, beta-adrenergic blockade with propranolol administration showed that sympathetic positive chronotropy was a critical compensatory factor around the upper limit of the CL of IHRp.(ABSTRACT TRUNCATED AT 250 WORDS)