[Clinical significance of electrophysiologic drug testing in the longterm therapy of class I, III and IV antiarrhythmic drugs for recurrent ventricular tachyarrhythmia].
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Biomedical subjects
Publications and source records attributed to J Umemura.
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Interactions of alpha-aminoisobutyric acid containing antibiotic peptides, trichopolyn I and hypelcin A with phosphatidylcholine bilayers were investigated to obtain some basic information on their bioactive mechanisms. Trichopolyn I as well as hypelcin A induced the leakage of a fluorescent dye, calcein, entrapped in sonicated egg yolk L-alpha-phosphatidylcholine vesicles. A quantitative analysis revealed that both the binding affinity and the 'membrane-perturbing activity' of trichopolyn I to the vesicles are about one-third of those of hypelcin A. The conformations and the orientations of the peptide and lipid molecules in the membranes were studied using polarized Fourier transform infrared-attenuated total reflection spectroscopy, circular dichroism, and differential scanning calorimetry. In phosphatidylcholine bilayers, both peptides mainly conformed to helical structures irrespective of the membrane physical state (gel or liquid-crystalline). The helix axes, penetrating the hydrophobic region of the bilayers, were oriented neither parallel nor perpendicular to the membrane normal. The disruption in the lipid packing induced by the peptide insertion seems to be responsible for the leakage by these peptides.
Study of the effects of fulgurating electric shocks on an isotropic protein gel more supple than ordinary myocardium provides better understanding of the mechanical effects of fulguration on biological tissues. With a shock and energy level of the type used clinically, a central crater is produced measuring 4 to 6 mm in diameter and a few millimetres deep, surrounded by a crown 30 mm in diameter. Damage due to the mechanical effects of fulgurating shocks is thus 3 to 15 times greater than the size of the electrode. The size of lesions is generally proportional to the energy level and is greater at the anode than cathode. It is also greater with impulses having a short rise time. When the electrode is almost parallel to the wall, the surface area of mechanical lesions is larger and more irregular and it is less deep than when the electrode is perpendicular to the gel.
A randomized, controlled study was conducted to compare the radiographic efficacy, safety and usefulness of ioversol and iopamidol in 146 patients undergoing angiocardiography at six institutions. The hemodynamic and electrocardiographic effects were clinically insignificant and comparable for both agents. Ioversol demonstrated lower incidence of adverse reactions and less heat sensation in left coronary arteriography than those with iopamidol. Overall radiographic efficacy with ioversol was slightly better than with iopamidol, according to the evaluation by both investigators and committee members. Ioversol appears to be very useful for angiocardiography. This comparative study demonstrated the value of safety and efficacy evaluation criteria suggested by the preceding clinical trial with ioversol.
A multi-center clinical study of a new nonionic iodinated contrast medium (ioversol) was performed in 26 patients undergoing left ventriculography (LVG) and coronary angiography (CAG) at four centers. The aims of this study were to try to establish a clinical evaluation method on contrast media in angiocardiography and to determine radiographic efficacy and safety of ioversol. The reliability of the method evaluating the radiographic quality of the contrast medium was also examined with statistical analysis. Excellent radiographic efficacy was observed with ioversol and morphological diagnosis was possible in all cases. The electrocardiograms (ST-segment deflection, T-wave amplitude, QT interval, corrected QT interval, arrhythmia and heart rate) and the hemodynamic parameters (left ventricular systolic and end diastolic pressures, left ventricular dp/dt max, aortic systolic and diastolic pressures) indicated no clinically significant changes. This study suggested that the monitoring of the ECGs and hemodynamic parameters for up to three minutes after injection of the contrast medium is sufficient for the evaluation in LVG and CAG, and that the monitoring in CAG during the first injection into each left and right coronary artery is also sufficient for the purpose. Heat sensation during injection was mild. A patient had a symptom of nausea after ioversol administration, but it was mild and transient and resolved spontaneously. There were no abnormal clinical laboratory data related to ioversol. The reliability of the radiographic quality evaluated by the individual clinical investigators was considered to be high and adaptable. However, the evaluation in the blinded cinefilms by the committee members involving all investigators would be more preferable for the higher objectivity. The study results suggest that ioversol is considered to be the efficacious and safe contrast medium for the cardiovascular angiography.
Polarized Fourier-transform infrared-attenuated total reflection spectroscopy has been applied to explore the temperature-dependence of molecular orientations in multibilayers of 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC) of various degrees of hydration. The order parameter of the hydrocarbon chain, evaluated from the dichroic ratios of the antisymmetric and symmetric CH2 stretching bands, was drastically decreased at the main (or gel to liquid-crystalline phase) transition temperature (Tm) irrespective of the water content, suggesting that the hydrocarbon chain is in a disordered state as a result of chain-melting associated with an increase in the number of the gauche conformers. On the other hand, the dichroic ratios of the polar bands of hydrated DPPC assignable to the symmetric PO2- stretching and asymmetric N+ (CH3)3 stretching modes were increased mainly at the pretransition temperature (Tp), except for less hydrated case. The dichroic ratios of both the OH stretching and OH2 bending bands of water showed the same temperature-dependence as those of the polar bands. These results indicate that the pretransition is ascribable mainly to the reorientation of the polar groups of the DPPC and bound water, while the main transition is due to the orientational disorder of the hydrocarbon chains. For less hydrated DPPC, the reorientation of the polar groups and water did not occur around Tp, but in the higher temperature region around Tm. This is in accord with the previously reported observation that the pretransition disappears for less hydrated DPPC. In this case, the polar groups and water may reorient following the reorientation of the hydrocarbon chains near Tm.
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The effect of hydration on the structure and molecular orientation of multibilayers of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC), cast on a germanium plate, was studied by means of polarized Fourier transform infrared (FT-IR)-attenuated total reflection spectroscopy. Compared with the dry state, the antisymmetric and symmetric CH2 stretching bands of fully hydrated DMPC in the liquid-crystalline state were shifted to the higher frequency side, indicating the increase in the number of the gauche conformers. However, the dichroism of these bands revealed that the hydrocarbon chains of DMPC were still ordered and titled. The absorption bands of the glycerol ester, phosphoryl, and choline groups were broadened upon hydration, suggesting the activation of the librational or torsional motion. Furthermore, the dichroism of the polar head group bands of DMPC indicated that these groups retained a slight orientation even in the fully hydrated and fluid multibilayers.
Regional left ventricular work is a more precise indicator of function than is simple shortening fraction. Regional work of the ventricle normalized to a unit volume of myocardium (RWM) is given by the following equation: RWM = - intergral of sigma d[ln(1/H)], where sigma is the mean wall stress and ln(1/H) is the natural logarithm of reciprocal of wall thickness. This method has been previously validated in animal experiments and it is now extended to the clinical setting for the first time. In 10 normal subjects and 6 patients with anteroseptal myocardial infarction, ventricular minor axis and wall thickness were measured by echocardiography and recorded simultaneously with high fidelity left ventricular pressure. Then, regional work of the interventricular septum and of the posterior wall of the left ventricle was calculated from the measured pressure and dimension data. In normal subjects, regional work of the septum and posterior wall was 6.1 +/- 1.7 and 7.0 +/- 1.8 mJ/cm3, respectively; the average of the septal and posterior wall regional work multiplied by the left ventricular myocardial volume correlated well (r = 0.93) with the total mechanical work done by the entire left ventricle. In patients with anteroseptal infarction, septal regional work was greatly reduced (0.6 +/- 1.7 mJ/cm3), compared with posterior wall regional work in the same patients (6.1 +/- 1.8 mJ/cm3). This simple method can be applied clinically in assessing the functional state of different regions of the myocardium.
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Continuous wave (CW) Doppler ultrasound has facilitated accurate estimates of pressure gradient (PG) across a stenotic valve. However, the severity of stenosis cannot be assessed using PG alone because it is dependent on actual flow across the valve. In this study, Doppler techniques were used to predict PG and aortic valve areas (AVA) in adults with aortic stenosis (AS). Fifty-four adult patients undergoing cardiac catheterization for suspected AS were prospectively evaluated. There were 28 men and 26 women, who ranged in age from 25 to 68 years with a mean of 56 years. These Doppler ultrasound studies were performed using a 2 MHz transducer and an Aloka SSD-730. With CW Doppler ultrasound, the highest velocities of the aortic jet were recorded from an apical approach. Left ventricular outflow flows were recorded about 1.0-1.5 cm below the aortic annulus using high PRF. Doppler waveforms were analyzed for the AT/ET (AT: acceleration time, ET: ejection time), and Doppler PG was calculated from the maximum velocity (V) of the aortic jet based on a modified Bernoulli equation (PG = 4V2), and aortic valve area was obtained using the continuity equation-(AVA = left ventricular outflow tract stroke volume divided by AS jet velocity integral). These data were compared with hemodynamic data obtained from cardiac catheterization. The following results were obtained: 1. In eight patients with substantial aortic regurgitation, whose maximum catheter PG were from 20 to 45 mmHg, the AT/ET was less than 0.30. The ratio of AT/ET correlated with the peak velocity of the aortic jet (r = 0.88) and the maximum PG (r = 0.87) obtained from cardiac catheterization. 2. In 46 patients with AS, the maximum PG by CW Doppler showed an excellent correlation with maximum catheterization PG (r = 0.97, SEE 6 mmHg), and the mean PG as calculated by the two techniques also disclosed a good correlation (r = 0.97, SEE 5.4 mmHg).(ABSTRACT TRUNCATED AT 400 WORDS)
Polarized Fourier transform infrared (FTIR)-attenuated total reflection (ATR) spectroscopy was applied to study the orientation of the linear pentadecapeptide antibiotic gramicidin D incorporated into phospholipid multibilayers, which were cast on a germanium ATR plate from chloroform solution. In DMPC and DPPC multibilayers, the CH2 stretching bands of lipid hydrocarbon chains were slightly shifted to the higher frequency side and bandwidth was increased in the presence of gramicidin. However, in DPPE multibilayers, frequencies and bandwidths of these bands were unaltered. In each case, gramicidin produced little effect on the orientation of lipid hydrocarbon chains, suggesting that gramicidin penetrates into lipid layers without noticeable perturbations. Upon incubation of cast films in contact with water above the gel-liquid-crystalline transition temperature (Tc) of lipids, the reorientation of gramicidin in lipid multibilayers occurred, the degree thereof depending upon the fluidity of the lipid hydrocarbon chains and the amount of surrounding water. In DMPC multibilayers, the helix axis of gramicidin was oriented almost parallel to the lipid hydrocarbon chains after incubation. In DPPC multibilayers, on the other hand, the helix axis of gramicidin was tilted on average about 15 degrees from the lipid hydrocarbon chains after incubation. However, in DPPE multibilayers, which are known to have the most rigid bilayer structures, the reorientation of gramicidin could not be seen.
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Addition of NaN3 to ferric protohemin biscoordinated with 1-methylimidazole (1-MeIm) or 2-methylimidazole (2-MeIm) in (CH3)2SO resulted in sizeable visible absorption changes, corresponding to the formation of the mixed ligand complexes, hemin X N-3 X 1-MeIm and hemin X N-3 X 2-MeIm. The visible absorption spectrum of the 1-MeIm complex was closely similar to those of azide hemoproteins, while the 2-MeIm derivative exhibited intensified 500 and 625 nm bands and depressed 540 and 570 nm peaks. The iron-bound N-3 of the model complexes exhibited two infrared stretching bands, which were assigned to the high- and low-spin peaks. The intensity of the high-spin infrared peaks increased at higher temperature. From the analyses of the infrared spectral changes, the thermodynamic values of the thermal spin equilibria were determined to be delta H = -3920 cal/mol and delta S = -11.1 e.u. for hemin X N-3 X 1-MeIm and delta H = -2150 cal/mol and delta S = 7.9 e.u. for hemin X N-3 X 2-MeIm. The thermodynamic values of the 1-MeIm complex are similar to the reported values for azide metmyoglobin, suggesting that the contribution from the nonbonded porphyrin-globin contacts to the spin equilibrium is small in azide metmyoglobin. Comparison of the delta H and delta S values among model systems indicates that delta H and delta S compensation similar to that observed in hemoprotein also holds in the models. This may suggest an underlying common denominator for the spin-equilibrium mechanisms in hemins and hemoproteins.