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Biomedical subjects

F Ohsuzu

Publications and source records attributed to F Ohsuzu.

At least 73 records · Page 4Linked to original sources

Protective effects of verapamil and adenosine treatment on high energy phosphate metabolism in ischemic and reperfused myocardium.

Isolated rat hearts were subjected to retrograde perfusion to investigate the protective effects of adenosine and verapamil on the myocardium. In group 1, the perfusate was standard Krebs-Henseleit buffer solution. The perfusate was changed to Krebs-Henseleit buffer containing verapamil (100 nM) in group 2, adenosine (100 microM) in group 3 and both drugs in combination in group 4 for 30 min before ischemia and during 20 min of reperfusion. Group 2 displayed a recovery of creatine phosphate but not of ATP at the end of reperfusion. In group 4, the recovery of both ATP and creatine phosphate was significantly greater than in group 1. The coronary flow of group 4 was significantly higher than that of the other groups. Treatment with both verapamil and adenosine before and after global ischemia may protect the ischemic myocardium by improving high energy phosphate metabolism and coronary circulation.

Adenosine↗

[The present state of arts and the future prospects of coronary angioscopy].

The angioscope catheter is 1.55 mm in outer diameter and 1.2 m in length. This distal end is tapered, therefore its outer diameter decreased to 1.1 mm. It has an inflatable balloon at the distal tip and four circular channels. Through one of the lumina, 0.014 inch PTCA guide wire can be used. The steerable guide wire enable the angioscope to be inserted to the target lesion safely and accurately. Recently we investigated the appearance of coronary artery in acute coronary syndromes. The results have indicated that thrombi, intimal irregularities, and xanthomatous atheromas were observed more frequently in patients with acute myocardial infarction, recent myocardial infarction and unstable angina. It is concluded that a thrombus overlying a rupture in the lining of plaque plays a major role in an acute coronary disorders, and that the fragile, lipid-rich gruel atheroma may procede its rupture. Coaxial alignments of the coronary artery were obtained in more than 80% of attempted patients. However, a finer controllable distal tip to allow good coaxial alignment and a larger balloon to reduce the coronary good flow and make the angioscopic catheter easier to track, are necessary for more complete visualization.

Angioscopy↗

Early release of neutrophil chemotactic factor from isolated rat heart subjected to regional ischaemia followed by reperfusion.

OBJECTIVE: The study was designed to demonstrate the time course of neutrophil chemotactic factor (NCF) release from blood-free isolated rat hearts and to clarify the characteristics of NCF in order to facilitate its identification. METHODS: Coronary effluents were collected every minute from Langendorff perfused rat hearts during ligation of the left coronary artery for 40 min and reperfusion for 60 min. The neutrophil chemotactic activity in the effluents was assayed using modified Boyden's chambers with rat neutrophils isolated from peripheral blood as the indicator cells. RESULTS: The NCF release started at 10 min of coronary artery occlusion. During the reperfusion period, NCF release peaked at 5 min (230% of preischaemic value). To clarify the characteristics of NCF, the changes in chemotactic activity were examined using various inhibitors and inactivators of possible NCF candidates (LTB4, PAF, 5-lipoxygenase, and thromboxane synthase). The heat stability of NCF was also examined to exclude heat labile molecules such as adenosine or complements appearing as NCF. Among the various substances examined, only PAF antagonists (CV-6209 and TCV-309 at concentrations of 10(-6) M and 10(-5) M respectively) abolished the chemotactic activity. However direct measurement of PAF in the effluents was unsuccessful. CONCLUSION: NCF is released from the heart early after ischaemic insult, with the highest peak occurring at 5 min of reperfusion. PAF related substances might be the primary NCF in the effluent but this remains to be determined.

Animals↗

Iodine 125-phenylpentadecanoic acid and its beta-methyl substitute metabolism in cultured mouse embryonal myocytes--iodine-labelled fatty acids as tracers of myocardial high energy phosphate.

Iodine-labelled fatty acids have been proposed as new tracers of cardiac metabolisms. However, it is not clear how these tracers would reflect the intracellular metabolism. Therefore, we measured the uptake and release of iodine 125-labelled phenylpentadecanoic acid (IPPA), its beta-methyl substitute (BMIPP) and 201Tl in cultured myocytes of mouse embryos, and compared these values to intracellular adenosine triphosphate (ATP) content after metabolic inhibitions of oxidative phosphorylation by sodium cyanide (CN), glycolysis by 2-deoxyglucose (2-DG) or fatty acid beta-oxidation by lactate. The uptake and release of BMIPP was not changed by any inhibitors suggesting BMIPP would not be metabolized in the myocytes. The uptake of IPPA was significantly reduced by 2DG and 60-80% of IPPA was metabolized to hydrophilic catabolites. The correlation of BMIPP and IPPA uptake to intracellular ATP content were high (r = 0.89, p < 0.05; r = 0.86, p < 0.1), but there was poor correlation of 201Tl to ATP values (r = 0.53, n.s.). These results suggested that iodine-labelled fatty acids could be used as better tracers of myocardial metabolism than 201Tl.

Adenosine Triphosphate↗

Enhanced myocardial adenylate cyclase activity in spontaneously hypertensive rats.

This study was designed to clarify the state of beta-adrenergic signal transduction and the disordered level of its transduction in hypertensive hearts, using myocardium from spontaneously hypertensive rats (SHR) as a generic model of essential hypertension. Beta-adrenergic receptor binding sites and dissociation constants in the extracted membranes of adult (70-100 days of age) SHR heart were not significantly different from those of Wistar-Kyoto (WKY) rats, the non-hypertensive control. The adenylate cyclase activities stimulated by isoproterenol with GTP, NaF and forskolin were significantly higher in SHR compared to those in WKY. To determine whether differences in signal transduction are natural or are a result of hypertension, we evaluated chronotropic responses in cultured cells of fetal hearts which had not been exposed to hypertension. Fetal cardiac muscle cells of SHR were more sensitive than WKY to isoproterenol stimulation over a wide concentration range. However, there were no statistically significant differences between these two strains with respect to the density of binding sites. These results suggest that in the transduction of adrenergic signals, alterations distal to the beta-receptors are present in the adult hearts of hypertensive rats, and, that the adrenergic signal transduction is already exaggerated in the pre-hypertensive fetal stage.

Adenylyl Cyclases↗

Differential extractability of creatine phosphate and ATP from cardiac muscle with ethanol and perchloric acid solution.

To compare the extractability of creatine phosphate with that of ATP by alcohol extraction, both compounds were extracted from normal perfused rat heart tissues by using various stepwise concentrations of ethanol and 0.4 M HClO4. Powdered samples (6-15 mg wet wt) from the freeze-clamped tissues were homogenized in 2 ml of the ethanol solutions. After centrifugation, the supernatant was removed; each centrifuged sediment was rehomogenized with 2 ml of 0.4 M HClO4 and centrifuged. The supernatant was neutralized with 0.4 m KHCO3. The same powdered samples were directly homogenized with 2 ml of 0.4 M HClO4 and treated in the same manner. Only a small amount of ATP in the tissues was extracted by an 85% or higher concentration of ethanol. Further, about 13% of the tissue ATP was not extractable by the subsequent perchloric acid extraction. In contrast to ATP, creatine phosphate in the tissues was partially extracted by 95% ethanol and nearly all of the tissue creatine phosphate was extracted by 70% ethanol. The total creatine phosphate obtained by 70% ethanol and by subsequent perchloric acid extraction was significantly higher than that obtained by direct perchloric acid extraction. From these results, it was concluded that the extractability of creatine phosphate in the tissue by alcohol extraction is clearly different from that of ATP. Additionally, the stepwise extraction is recommended as a useful method for the extraction of energy metabolites in perfused rat heart tissue.

Adenosine Triphosphate↗

[Diagnosis of left ventricular aneurysm by exercise thallium-201 myocardial single photon emission computed tomography].

To diagnose and characterize post-infarction left ventricular aneurysms, we performed exercise thallium-201 myocardial single photon emission computed tomography (SPECT) combined with selective coronary angiography and left ventriculography. The subjects consisted of 79 patients with acute myocardial infarction; 42 with anteroseptal, three with both anterior and inferior, 29 with inferior and five with posterior infarction. Visual classification of ventricular wall morphology by either a horizontal or a vertical long-axis image was designed into convergent (C), parallel (P) and divergent (D) types, according to the interrelationship between either septal and lateral wall or anterior and inferior wall, respectively. This method was applied in post-stress and delayed images, and these patients were divided into five groups (Group A-E) in accordance with varying morphological types from the post-stress to the delayed as follows: C-C (Group A, 36 patients), P-C (Group B, 8), P-P (Group C, 7), D-P (Group D, 5) and D-D (Group E, 23). A high incidence (21/23) of a left ventricular aneurysm by left ventriculography was recognized in Group E patients in comparison with other Groups. Provided that either Group D or E (all patients had anterior infarction) had left ventricular aneurysms, the diagnostic sensitivity, specificity and accuracy were 89%, 92% and 86%, respectively. Two of three patients with false negative diagnosis had only apical involvement. Furthermore, these two Groups had significantly larger defect scores as calculated by polar maps than did the other three Groups. When patients with anterior infarction with defect scores of 200 or greater were defined positive, the sensitivity, specificity and accuracy of ventricular aneurysms were 96%, 75% and 86%, respectively. One false negative case was apical infarction, and one of the two false positive cases were extensive anteroseptal infarction involving the apex. These results suggest that a left ventricular aneurysm which is important in predicting prognostic sequence could be diagnosed only by exercise SPECT, and that it could be characterized by extensive and severe apicoanterior infarction and a divergent-type ventricular wall arrangement on a post-stress SPECT image.

Exercise Test↗

Effects of calcium antagonists and free radical scavengers on myocardial ischemia and reperfusion injury: evaluation by 31P-NMR spectroscopy.

The Langendorff perfused rat heart was used to investigate whether myocardial damage during ischemia and reperfusion could be protected by free radical scavengers, calcium antagonist and adenosine. Myocardial high energy phosphates were measured by phosphorus-31 NMR spectroscopy during normal perfusion, 20 min of ischemia and 20 min of reperfusion. In hearts, which were treated both with free radical scavengers (FRS) (Superoxide dismutase): 24 IU/ml and catalase 22 IU/ml) and verapamil (10(-7) M), beta-ATP was significantly higher than that of FRS at the end of ischemia. However, beta-ATP recovered only to 83% of baseline value at the end of reperfusion. In view of myocardial metabolism, verapamil treated hearts were good for recovery of creatine phosphate (PCr) but not ATP at the end of reperfusion. Hearts which were treated with only adenosine did not differ from control hearts. However, when hearts were treated with both verapamil and adenosine (10(-4) M), recovery of both ATP and PCr content was significantly greater than that of control hearts. These results suggested that pretreatment with both verapamil and adenosine before and after global ischemia could protect ischemic myocardium, but, further studies are necessary to clarify the precise mechanism of protection.

Adenosine↗

[Quantitation of the severity of coronary artery disease using thallium-201 tomographic scores].

To evaluate coronary artery disease, a new quantitative thallium-201 (201T1)-tomographic scintigraphic score (TSS: modified Massie's score) using oxygen consumption (METS) was developed and compared with coronary angiographic score (CAG-S) in 27 patients (eight patients with normal coronary angiograms, and five, eight and six patients with one, two and three vessel disease, respectively) without previous myocardial infarction. All patients received both coronary angiography and the treadmill exercise test using 201T1-myocardial single photon emission computed tomography (SPECT) within two weeks. The redistribution area (RA) and washout rate area (WA) were derived from the circumferential profile analysis using apical (A), midventricular (M) and basal (B) short-axis images. To obtain TSS values, the sum of these values was divided both by percentage of the age-predicted maximal heart rate (%PMHR) and the METS value as follows: TSS = [RA (A, M, B) + WA (A, M, B)]/(%PMHR x METS). The results were as follows: 1. TSS values were 6.4 +- 1.6, 9.4 +/- 2.2, 24.2 +/- 12.0 and 30.6 +/- 5.0 (mean +/- SD) in normal, one, two and three vessel disease groups, respectively. Significant differences were found among each group except between two and three vessel disease groups. 2. The detectability of significant coronary artery disease was 89% (17/19) except in two patients with one vessel disease. 3. A high correlation coefficient was found between TSS (X) and CAG-S (Y), i.e., Y = 0.8X - 3.5 (r = 0.944, p less than 0.001). It was concluded that the tomographic scintigraphic score (TSS) is useful not only for detecting, multivessel disease but also for totally-evaluating its severity, extent and influence on collateral supply, and could be used for analyzing prognosis and the selection of therapeutic interventions.

Aged↗

Evolutionary changes in left and right ventricular function in acute myocardial infarction.

To determine the evolutionary changes in right and left ventricular function in acute myocardial infarction, 3 serial gated blood pool scans were performed in 76 patients within 24 hours (24 H), at 10 days (10 D) and 3 months (3 M) following the onset of myocardial infarction. The patients were divided into 3 groups: ANT (anterior MI), INF (inferior MI without right ventricular dysfunction) and RVF (inferior MI with right ventricular dysfunction). LVEF in ANT was significantly lower than that of INF and RVF at 24 H, 10 D and 3 M. The ratio of right ventricular volume to LV volume (RVV/LVV) was compared among 3 groups. The mean values of RVV/LVV in RVF were 1.3 through 24 H and 3 M and they were significantly higher than the other two groups. The RVV/LVV in ANT and INF were around 1.0. LVEDVI in RVF was rather smaller than that of ANT and INF. LVESVI in ANT at 24 H was significantly larger than that of INF and RVF and the mean value of LVESVI in ANT were around 60 ml/M2 from 24 H to 3 M. LVEF in ANT, RVF and INF did not increase significantly during peak exercise at 3 M. However, quantitative regional wall motion analysis revealed that regional wall motion of R2 (posterolateral wall motion) in ANT and R5 (septal wall motion) in INF decreased significantly during peak exercise. These impairments in regional wall motion might be due to the exacerbation of ischemia of non-infarcted area.

Adult↗

[Radionuclide ventriculographic evaluation of left ventricular systolic function in acute myocardial infarction].

Within 18 hours of acute myocardial infarction, global left ventricular (LV) function was evaluated by radionuclide ventriculography for 127 patients. Ejection fraction (EF) was calculated using a variable region of interest counts method. LV end-diastolic volume index (EDVI) was calculated from the LV outlines in the anterior and LAO projections using the area-length method. To validate the determination of EDV by the area-length method, the radionuclide EDV correlated with that derived from direct contrast angiography in 44 other patients who had both studies within two weeks, with an overall correlation coefficient of 0.84. To minimize any potential problems with the geometric ellipsoid model, the end-systolic volume index (ESVI) was calculated from EF and EDVI. Peak systolic blood pressure (PSP) was recorded with a cuff during imaging and the PSP/ESV calculated as a measure of LV contractile function. The regional wall motion of five segments in both the anterior and LAO projections were each scored on a scale, from 4 (= normal) to 0 (= dyskinesis). The wall motion index (WMI) derived from the sum of the 10 segment scores represented an overall index of wall motion (maximum = 40). In addition, the more widely used % abnormally contracting segments (%ACS) was calculated. The severity of wall motion abnormalities were associated with significant increases in heart rate and ESVI, whereas EDVI began to increase under more severe damage to the myocardium. Our data are consistent with those of Klein who found that the LV enlarges only when 20 to 25% of the surface area is rendered akinetic. There were significant decreases in EF and PSP/ESV with moderate reduction in wall motion, and the relation between EF and PSP/ESV was curvilinear. Information about ventricular volume and systolic blood pressure might be of additional value to EF for a more complete understanding of the changes in the functional state of the LV. Global LV function was compared between anterior and inferior myocardial infarcts. The size of %ACS was larger in anterior than in inferior infarction and a greater decrease in WMI in the former suggested larger infarct size in anterior infarction. As a result, ESVI was significantly larger in anterior infraction than in anterior infraction. However, an increase in EDVI was not significantly different between the two groups. EF was reduced to a greater extent in anterior than in inferior infarction. The overall data indicate that patients with anterior infarction have more severe impairment of left ventricular global function than do those with inferior infarction.

Cardiac Volume↗

The lung beta-receptor in the spontaneous hypertensive rat.

The basic mechanism underlying the abnormal systemic vascular resistance in the spontaneously hypertensive rat (SHR) is poorly understood. To categorize the beta-receptor system in the lungs of these animals, we evaluated receptor number and affinity as an index of this subclass of beta receptors. The lung was chosen because it is not directly affected by the alteration in blood pressure and provides a ready supply of beta-receptors. The aortic blood pressure and heart rate were measured directly through cannulation of the carotid artery. Twenty-four hours later, lung membranes from the SHR and control animals were extracted and partially purified. The affinity and number of receptors were measured by saturation analysis employing 3H-dihydroalprenolol (3H-DHA). Scatchard analysis demonstrated that the number of receptors was identical and of a single class in both sets of animals. However, the beta-receptor from the SHR had a higher affinity than that of normal rats. It is not clear whether this represents an adaptive mechanism following the development of hypertension in the SHR or it represents a basic alteration in this strain of rat. Further studies aimed at categorizing the development of this defect during ontogeny as well as its physiologic consequences should prove valuable in understanding the mechanism of spontaneous hypertension.

Animals↗

Relation of segmental wall motion to global left ventricular function in acute myocardial infarction.

The relation of left ventricular regional wall motion to global ventricular function was evaluated by radionuclide ventriculography in 127 patients within 18 hours of acute myocardial infarction. No patient had evidence of previous myocardial infarction. The following parameters were measured: (1) wall motion index; (2) percent of abnormally contracting segment; (3) ejection fraction (EF); (4) end-diastolic volume (EDV) and end-systolic volume (ESV); and (5) peak systolic cuff pressure/end-systolic volume ratio (PSP/ESV). The measurements of global function correlated well with wall motion index (r = 0.83, p less than 0.001 for EF; r = -0.69, p less than 0.001 for ESV; and r = 0.061, p less than 0.001 for PSP/ESV), but EDV correlated less well (r = -0.35, p less than 0.001). Multiple linear regression analysis revealed that EF correlated best with wall motion index, and no other parameters of global left ventricular function added significantly to the regression. The correlation of motion in each segment with EF was determined by multiple linear regression analysis. Ejection fraction correlated best with motion in the anterobasal, then in order of correlation, in the apical-septal, inferoapical, anterolateral, and superlateral walls. The relation of EDV, ESV, and degree of percent abnormally contracting segments was as follows: EDV did not increase with a mild regional wall motion abnormality; however, ESV did increase and reduced stroke volume. As percent abnormally contracting segments worsened, enlargement of both EDV and ESV was seen and was associated with further reduction in systolic volume. These data suggest that EF is the best global left ventricular function correlate of the severity of the regional wall motion abnormality, and that abnormal motion in the territory of the left anterior descending coronary best predicts reduction in global left ventricular function. Radionuclide ventriculography is useful in characterizing global and regional left ventricular function in the early hours of acute myocardial infarction.

Aged↗

Postoperative thallium-201 myocardial images. Evidence of regression of right ventricular hypertrophy in man.

Thallium-201 myocardial scintigraphic studies were performed on 24 patients with chronic right ventricular overload before and after surgical correction of haemodynamic overload. The ages of the patients ranged from 20 to 65 years (mean 39 years) at operation. The degree of right ventricular visualisation remained essentially unchanged in an early postoperative study (four to 60 days), though a decrease in right ventricular cavity size was noted in patients with right ventricular volume overload. On later follow-up (18 to 36 months), thallium uptake in the right ventricle was definitely less than before operation in all 13 patients studied at this time. Because thallium-201 radioactivity reflects myocardial blood flow and mass, our study indicates that right ventricular hypertrophy is largely reversible. Thus, thallium-201 myocardial scintigraphy can be used to assess non-invasively regression of right ventricular hypertrophy in patients with right ventricular overload.

Adult↗

Relationship between changes in regional myocardial contraction and energy metabolism following coronary flow reduction.

To investigate the relationship between mechanical and metabolic deterioration in the ischemic myocardium following a decrease of coronary blood flow, the patterns of regional myocardial contraction and myocardial adenosine triphosphate (ATP) content were analyzed simultaneously in canine left ventricles with constriction of the left anterior descending coronary artery (LAD). The patterns of contraction in the ischemic region were monitored by means of ultrasonic dimension gauges implanted in the endocardial surface and were classified into 5 types; Type 0 = normal, Type I = late systolic lengthening, Type II = early and late systolic lengthening with end diastolic length elongation, Type III = systolic bulge with early diastolic shortening, and Type IV = holosystolic bulge. Type I developed in 6/8 dogs with 1-49% LAD flow reduction, Type II in 6/8 dogs with 50-74% reduction, and Types III and IV in all dogs with 75-100% reduction. The myocardial ATP content (microM/Gm tissue) at the sites of the patterns of myocardial contraction measurement was analyzed. No differences in ATP content were noted between Type 0 and Type I (3.70 +/- 0.51 vs. 3.60 +/- 0.36). In contrast, the ATP content in Type II was significantly reduced (2.94 +/- 0.20) compared to Type I (p less than 0.005). In Types III + IV with systolic bulge, the ATP reductions were severer (2.59 +/- 0.36) than in Type II (p less than 0.05). In conclusion, it can be said that as the LAD flow reduction advanced, the patterns of myocardial contraction were transformed from Type 0 to Type IV with accompanying ATP reductions.

Adenosine Triphosphate↗

The changes in pattern of myocardial shortening by reduction of regional coronary blood flow.

The relationship between the grade of a decrease in the regional coronary blood flow and the movement of ventricular myocardium of that region was investigated in open chest dog. Blood flow in left anterior descending artery (FLAD) was reduced by stepwise constriction of LAD with ligature. Ventricular segment length was measured in a circumferential plane on the endocardial surface by ultrasonic dimension system. For the elimination of the noise caused by ultrasonic dimension system, the synchronizer was inserted between sample clock of the dimension system and the trigger circuit of the electromagnetic flowmeter. A 20% reduction of FLAD affected the pattern of ischemic myocardial shortening very little. Discontinuance of shortening to the end of systole was occurred by a 20 to 60% reduction in FLAD. Early and/or late systolic bulging was induced by a 60% reduction of FLAD. Systolic bulging with early diastolic shortening was seen in the cases with a 60 to 80% reduction in FLAD. Frank systolic bulging which was always seen by complete occlusion of LAD was produced by a 60 to 90% reduction of FLAD in few cases.

Animals↗