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Biomedical subjects

T Kumada

Publications and source records attributed to T Kumada.

At least 145 records · Page 8Linked to original sources

Quantitative analysis of contraction band and coagulation necrosis after ischemia and reperfusion in the porcine heart.

To assess the importance of contraction band necrosis (CBN) in reperfusion, CBN, coagulation necrosis (CN), and infarct size, expressed as CBN + CN, were quantitatively analyzed in 25 porcine hearts without collateral circulation. The left anterior descending coronary artery was ligated for 20, 30, 60, and 120 min and then reperfused for 8 hr (groups 1 to 4, respectively). Five hearts were not reperfused (group 5). The areas of CBN and CN were traced at a magnification of X 100 under an inverted microscope and quantified with use of an image analyzer. There was no change in hemodynamics with either occlusion or reperfusion. Regional myocardial blood flow, measured by the generated hydrogen gas clearance method, decreased to almost zero after occlusion but recovered during reperfusion. Percent of risk area infarcted in groups 1 to 4 was 0 +/- 0%, 11 +/- 7%, 80 +/- 9%, and 96 +/- 2%, respectively, and the percent of risk area infarcted in group 4 was the same as that in hearts subjected to permanent occlusion (95 +/- 3%). The percent area of CBN was 100 +/- 0% in group 2, 68 +/- 11% in group 3, 2 +/- 1% in group 4, and 2 +/- 2% in group 5. In group 3, the inner third of the ischemic left ventricular wall showed CN and the middle and outer third CBN. These findings show that in pig hearts without collateral circulation, the transmural infarct, two-thirds of which is occupied by CBN, is evident even when reperfusion is achieved after 1 hr occlusion. Therefore, protection against CBN might reduce infarct size after reperfusion.

Animals↗

Studies on the monoexponential nature of the left ventricular pressure fall during isovolumic relaxation period in the diseased heart.

Our recent clinical studies on the negative dP/dt upstroke pattern suggested that the left ventricular pressure (LVP) deviated from the exponential curve during isovolumic relaxation period (IRP) in diseased hearts. To examine this further two types of monoexponential curve fitting were done in various heart diseases (normal (N): 8, angina pectoris (AP): 8, myocardial infarction (MI): 13, hypertrophic cardiomyopathy (HCM): 10, dilated cardiomyopathy (DCM): 8). LVP was measured by a Millar's catheter-tip transducer, and four types of time constant (T1-T4) were derived: T1 was calculated by an exponential curve fitting e-t/T1 + B (B is constant), T2 by the ratio Pm/peak (-) dP/dt (Pm is LVP at peak (-) dP/dt), T3 by the best exponential curve fit e-t/T3 + B + C (C is constant), and T4 by the ratio (Pm-C)/peak (-) dP/dt. If the exponential curve fitting was reasonable, the relation between T1 and T2, or T3 and T4, should be on the line of identity. The result was as follows: T2 = 1.4 T1 - 6.1 (r = 0.84) and T4 = 1.1 T3 - 10.7 (r = 0.94). Additionally, C (mmHg) in MI (-26 +/- 15), HCM (-36 +/- 19) and DCM (-32 +/- 20) were lower (p less than 0.05) than in N (-13 +/- 7). These findings suggest that the LVP during IRP could deviate from the monoexponential curve and that careful attention should be given to calculate the time constant in diseased hearts.

Adult↗

[Microcomputer control of a LED stimulus display device].

A visual stimulus display system controlled by a microcomputer was constructed at low cost. The system consists of a LED stimulus display device, a microcomputer, two interface boards, a pointing device (a "mouse") and two kinds of software. The first software package is written in BASIC. Its functions are: to construct stimulus patterns using the mouse, to construct letter patterns (alphabet, digit, symbols and Japanese letters--kanji, hiragana, katakana), to modify the patterns, to store the patterns on a floppy disc, to translate the patterns into integer data which are used to display the patterns in the second software. The second software package, written in BASIC and machine language, controls display of a sequence of stimulus patterns in predetermined time schedules in visual experiments.

Animals↗

The post-antimicrobial suppressive effect of quinolone agents.

A post-antimicrobial effect (PAE) was seen with all of the new 4-quinolones studied: ciprofloxacin, ofloxacin, Cl-934, Ro 23-6240, A-56619 and S-25930. The post-antimicrobial suppression of growth was for 4-8 h in the case of Escherichia coli, Klebsiella pneumoniae, Serratia marcescens and Pseudomonas aeruginosa. PEA was demonstrated both in Mueller-Hinton broth at pH 7.4 and in urine at pH 5.5 with a Mg2+ concentration of 9.5 mM. Resistant organisms, with MICs greater than 4 micrograms/ml, showed a PAE after a 2-h exposure to 200 micrograms/ml of 4-quinolones. This demonstrates that PAE is seen for 4-quinolones even under conditions in which they are less active.

Anti-Bacterial Agents↗

[Relationship between interatrial pressure gradient and motion of the interatrial septum].

To evaluate interatrial septal motion throughout the cardiac cycle, echocardiograms of the septum were obtained by esophageal echocardiography simultaneously with left and right atrial pressures using Millar's micromanometers in nine subjects with sinus rhythm. There were four patients with atypical chest pain but with normal coronary arteries, two with old myocardial infarction, one with angina pectoris, one with aortic regurgitation and one with sick sinus syndrome. The relationship between interatrial pressure gradient (IAPG: left atrial pressure minus right atrial pressure) and the motion of the septum was examined. In all nine patients, the curves of IAPG showed two peaks near the second heart sound and during the atrial contraction period, and the motion of the septum throughout the cardiac cycle showed a similar pattern except during the late diastolic period. During atrial contraction the septum moved posteriorly (decrease in left atrial dimension) against the IAPG. Therefore, except during the atrial contraction period, the motion of the atrial septum is considered to be dependent on this pressure gradient. During the atrial contraction period, the direction of the septal movement might be dependent on the force of active contraction of the left atrial muscles.

Adult↗

Acute effects of sublingual isosorbide dinitrate on global and regional left ventricular diastolic filling in normal persons.

To study the acute effects of isosorbide dinitrate (ISDN) on global and regional left ventricular (LV) diastolic filling, gated radionuclide ventriculographic studies were conducted in 21 normal persons before and after sublingual administration of ISDN. ISDN treatment caused significant increases in ejection fraction and peak LV ejection rate and it caused a delay in occurrence of peak LV filling, without statistically significant changes in peak LV filling rate globally and regionally. The ratios of peak LV filling rate to peak LV ejection rate decreased significantly both globally and regionally. These alterations induced by ISDN could be interpreted as indicating a failure of improvement of the early diastolic filling despite increased systolic function and heart rate in the global left ventricle and in regions of the left ventricle. Furthermore, ISDN caused early diastolic asynchronous filling. There was a negative correlation between this early diastolic asynchronous filling and the ratio of global peak LV filling to global peak LV ejection rate (r = -0.66, p less than 0.001), indicating that administration of ISDN to normal persons may produce early diastolic asynchronous filling associated with failure of improvement of diastolic filling despite increased systolic function and heart rate.

Administration, Oral↗

Atrial filling fraction obtained by aortic root echocardiogram in man.

Atrial filling fraction obtained by left ventricular echocardiogram (AFF by LV echo) is considered to be a reliable measure of AFF of LV. However, in patients with LV asynergy, AFF by LV echo cannot be evaluated correctly by this method. To obtain AFF, we devised a new echocardiographic index of AFF, obtained from the aortic-left atrial echogram (AFF by Ao echo), and examined the significance of this index in 9 normal subjects (Normals) and 49 patients with various heart diseases. The correlation between AFF by Ao echo and left ventricular end-diastolic pressure (LVEDP) also was examined. In an additional 20 patients with acute myocardial infarction (acute MI), the relationship between AFF by Ao echo and pulmonary arterial end-diastolic pressure (PAEDP) was studied for several days following the onset of MI. Results were as follows: In Normal patients and patients without asynergy, a significant correlation was seen between AFF by LV echo and AFF by Ao echo (r = 0.710, p less than 0.001). The value of AFF by Ao echo was always greater than that by LV echo. AFF by Ao echo in patients with hypertensive heart disease (HHD), angina pectoris (AP) and old myocardial infarction (old MI) was significantly higher than that in Normal patients. A significant curvilinear correlation was seen between AFF by Ao echo and LVEDP (r = 0.673, p less than 0.005). In patients with acute MI, AFF by Ao echo correlated well with PAEDP.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Pharmacokinetic studies on the concomitant administration of piperacillin and cefazolin, and piperacillin and cefoperazone in rabbits.

The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.

Animals↗

Fibrinolytic action of a new semi-synthetic polysaccharide sulfate, galactan polysulfate (DH 6322), in the rat.

Galactan polysulfate, DH 6322, when added to rat plasma, shortened euglobulin clot lysis time through both increase in the recovery of plasminogen activator activity in euglobulin precipitates and direct acceleration of fibrinolysis. DH 6322 treatment also resulted in accelerating plasma clot lysis induced by urokinase. The effect of DH 6322 was further studied with a purified system composed of bovine fibrinogen and plasminogen. In this system, DH 6322 was found to be a potent stimulator of both fibrinolysis and fibrinogenolysis induced by urokinase. The activation process of plasminogen was not affected by DH 6322 even in the presence of fibrin or fibrinogen. The accelerating effect of DH 6322 on fibrinolysis in the purified system was scarcely affected by addition of plasma antifibrinolytic factors. DH 6322 also stimulated fibrin clot lysis induced by a low concentration of purified plasmin in place of plasminogen and urokinase, and its accelerating effect was not observed in the presence of tranexamic acid. Formation of fibrin clot susceptible to generated plasmin was observed at relatively high concentrations of DH 6322 above 80 micrograms/ml. Additional experiments indicated that DH 6322 increased the amount of plasminogen bound to fibrin. These results suggested that DH 6322 stimulated fibrinolysis through increasing the binding of plasminogen or plasmin to fibrin.

Animals↗

Antithrombotic and thrombolytic effects of galactan polysulfate (DH 6322) in rats.

Anticoagulant, fibrinolytic and thrombolytic effects of galactan polysulfate (DH 6322), a new semi-synthetic polysaccharide sulfate of bacterial origin, were studied in the rat in vitro, ex vivo and in vivo. Addition of DH 6322 to citrated plasma gave a 50% reduction in euglobulin lysis time at around 50 micrograms/ml and a 2-fold prolongation in plasma recalcification time at 40 micrograms/ml. Intravenous injection of DH 6322 caused significant acceleration of euglobulin clot lysis and urokinase-induced plasma clot lysis at doses as low as 2 mg/kg, and also significant prolongation of plasma recalcification time. Oral application of the compound gave similar effects only at an extremely high dose of 3 g/kg. When injected intravenously before induction of pulmonary thrombosis by lactic acid infusion, DH 6322 was found to be effective in preventing thrombus formation. In progressive venous thrombosis induced by insertion of a steel coil into the inferior vena cava, DH 6322 treatment also caused a significant reduction of thrombus size together with increase in the serum levels of fibrin degradation products. The findings indicate that the antithrombotic effects of DH 6322 result from its enhancement of the fibrinolytic potential as well as its anticoagulative action.

Animals↗

In-vitro activity of ofloxacin, a quinolone carboxylic acid compared to other quinolones and other antimicrobial agents.

Ofloxacin is a new quinolone carboxylic acid compound. Its activity against 900 bacterial isolates was determined. It inhibited 90% of Escherichia coli, Klebsiella sp., Aeromonas hydrophila, Salmonella spp., Shigella spp., Citrobacter spp., Enterobacter spp., Morganella morganii, Proteus mirabilis, Yersinia enterocolitica at less than or equal to 0.8 mg/l. Branhamella catarrhalis, Haemophilus sp., Neisseria sp. were inhibited by less than or equal to 0.1 mg/l. Pseudomonas aeruginosa and other Pseudomonas species were inhibited by less than or equal to 6.3 mg/l. Although most staphylococcal species, including methicillin-resistant staphylococci were inhibited by 3.1 mg/l, many streptococcal species had higher MIC values, and most Bacteroides species were inhibited at less than or equal to 6.3 mg/l. The overall activity of ofloxacin was similar to enoxacin and norfloxacin. Ofloxacin inhibited organisms resistant to nalidixic acid, ampicillin, cephalexin, piperacillin, and gentamicin including Enterobacter spp., Citrobacter freundii and Serratia marcescens resistant to cefotaxime. The activity of ofloxacin was lower at an acid pH and in urine, but serum had no effect on MICs or MBCs. Increase in ofloxacin MICs for various bacteria could be achieved by repeated subculture in the presence of ofloxacin.

Animals↗

Comparison of aminoglycoside resistance patterns in Japan, Formosa, and Korea, Chile, and the United States.

The resistance mechanisms of more than 2,000 aminoglycoside-resistant gram-negative aerobic bacteria were estimated by a method that assigned a biochemical mechanism based on susceptibility to selected aminoglycosides. Strains from hospitals in Japan, Formosa, and Korea (the Far East) were compared with strains from Chile and the United States. Of the strains from Chile, 90% had an aminoglycoside resistance pattern indicative of the 3-N-acetyltransferase [AAC(3)-V] enzyme. Of the strains from the Far East, 78% had susceptibility patterns suggesting the presence of AAC(6') enzymes. In contrast, strains from the United States had a wider variety of resistance mechanisms including 2''-O-adenylyltidyltransferase [ANT(2'')], AAC(3), AAC(6'), and AAC(2'). Reflecting these differences in resistance patterns, the frequencies of resistance to gentamicin, tobramycin, dibekacin, and amikacin in strains from the United States were different from those in strains from the Far East. These differences seem to be correlated with different aminoglycoside usage in the two regions. In the United States, where gentamicin was the most widely used aminoglycoside, 92% of the strains were resistant to gentamicin, 81% were resistant to dibekacin, and 8.8% were resistant to amikacin. In the Far East, dibekacin and kanamycin were widely used in the past and more recently amikacin has been frequently used. Of the strains from this region, 99% were resistant to dibekacin, 85% were resistant to gentamicin, and 35% were resistant to amikacin.

Aminoglycosides↗

Severity of the regional wall motion and its effects on global left ventricular diastolic filling in patients with single-vessel coronary artery disease and previous myocardial infarction: assessment with radionuclide ventriculography.

The severity of the regional wall motion and its effects on the global left ventricular diastolic filling were analyzed with use of radionuclide techniques in 19 patients with isolated disease of the left anterior descending coronary artery with previous myocardial infarction. Regional maximum inward movements in the noninfarcted lateral region occurred at a time close to the global end-systole, but occurred far beyond the global end-systole in the infarcted septal and apical regions, resulting in the occurrence of the regional asynchronous wall motion between the infarcted and noninfarcted regions after the global end-systole. A positive correlation between this end-systolic asynchronous wall motion and the asynchronous filling in early diastole was found (r = 0.69, p less than 0.001). A negative correlation between the asynchronous filling in early diastole and the global peak filling rate was also found (r = -0.58, p less than 0.01). Thus, the end-systolic regional asynchronous wall motion causes the subsequent regional asynchronous filling in early diastole, which may cause impairment of the global left ventricular filling in patients with single-vessel coronary artery disease with previous myocardial infarction.

Adolescent↗