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Biomedical subjects

H Kusuoka

Publications and source records attributed to H Kusuoka.

At least 37 records · Page 2Linked to original sources

Detection of viable cortical neurons using benzodiazepine receptor imaging after reversible focal ischaemia in rats: comparison with regional cerebral blood flow.

To elucidate the utility of benzodiazepine receptor imaging for the detection of viable cortical neurons, dual-tracer autoradiography using iodine-125 iomazenil (IMZ) and iodine-123 N-isopropyl-4-iodoamphetamine (IMP) was performed in a model of reversible focal ischaemia during the acute and subacute phases. The right middle cerebral artery of anaesthetized rats was occluded for 60 min using an intraluminal filament and reperfused. In the acute phase study, 125I-IMZ (370 kBq) was injected via the femoral vein at 2 h after reperfusion, and 123I-IMP (37 MBq) was injected at 50 min post-injection. Rats were sacrificed 10 min after the injection of 123I-IMP. In the subacute phase study, the same procedure was performed at 5 days after reperfusion. In the acute phase, the IMP uptake was significantly decreased in almost all areas of the lesioned hemisphere, an exception being the cerebellum; however, the IMZ uptake was significantly decreased only in ischaemic cores. The discrepancy between IMZ and IMP uptake was observed in the lateral neocortex and the lateral caudate putamen (CPu), which were most frequently damaged in this ischaemic model. In the subacute phase, the IMZ uptake in lesioned rats was significantly decreased only in the parietal lobe and hippocampus, though the IMP uptake was decreased in many regions of lesioned hemispheres (the frontal, parietal cortex, CPu, hippocampus and thalamus). Histopathological findings indicated that both the IMP and the IMZ uptake was markedly decreased in necrotic areas. Although the IMP uptake was significantly decreased in the ischaemic areas, the IMZ uptake was maintained in these areas. These results suggest that benzodiazepine receptor imaging is superior to regional cerebral blood flow imaging for the detection of viable cortical neurons in both the acute and subacute phases of ischaemia.

Animals↗

Frequency-dependent changes in calcium cycling and contractile activation in SERCA2a transgenic mice.

OBJECTIVE: This study was undertaken to investigate the mechanism of altered contractility in hearts from transgenic mice overexpressing the sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2a). In particular, we sought to determine whether the reported increase in contractility is frequency-dependent, as might be expected if attributable to changes in SR Ca2+ loading. METHODS: Intracellular [Ca2+] and contractile force were measured at room temperature (22 degrees C) simultaneously in fura-2-loaded isometrically-contracting trabeculae dissected from the hearts of FVB/N control (n = 6) or SERCA2a transgenic (n = 6) mice. RESULTS: SERCA transgenics exhibit a positive force-frequency relationship, but this was flat in age- and strain-matched controls. SERCA transgenics exhibit a sizable increase in calcium transient amplitude relative to controls, with a concomitant increase in force generation at higher frequencies of stimulation. Amplitudes of Ca2+ transients (transgenics: 1.56 +/- 0.09 micromol/L, controls: 1.21 +/- 0.14) and twitches (transgenics: 21.71 +/- 0.91 mN/mm2, controls: 13.74 +/- 1.67) were significantly different at 2.0 Hz stimulation (P < 0.05). CONCLUSION: An increase in SERCA expression increases the ability of the sarcoplasmic reticulum to store calcium, such that more calcium is available to be released during each heartbeat at higher stimulation rates.

Animals↗

Kinetics of a putative hypoxic tracer, 99mTc-HL91, in normoxic, hypoxic, ischemic, and stunned myocardium.

UNLABELLED: 99mTc-4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime (HL91) was developed as a putative hypoxic reagent. This study focused on the myocardial kinetics of 99mTc-HL91 in various oxygen levels and perfusion states. METHODS: The time-activity curve of 99mTc-HL91 was measured in isolated perfused rat heart after the bolus infusion. RESULTS: 99mTc-HL91 was cleared quickly from normoxic hearts, and retention at 30 min after injection was 0.18 +/- 0.02 percentage injected dose per gram of wet weight (mean +/- SE; n = 6). When the concentration of oxygen bubbling through the perfusate was reduced from 100% to 50%, 20%, 5%, and 0%, retention of 99mTc-HL91 increased to 0.47 +/- 0.03 (n = 5), 0.48 +/- 0.03 (n = 5), 0.71 +/- 0.01 (n = 5), and 0.70 +/- 0.02 (n = 5), respectively (P < 0.05). Compartment analysis revealed that the trapping mechanism, which was dependent on tissue oxygen concentration, determined the retention rate. Although not retained in stunned myocardium (0.17 +/- 0.02, n = 5; P = not significant), 99mTc-HL91 was significantly retained when injected before ischemia (1.06 +/- 0.06, n = 5; P < 0.05). CONCLUSION: These results indicate that retention of 99mTc-HL91 correlates well with oxygen level in the perfusate, suggesting that the agent may be a useful marker of the severity of myocardial hypoxia.

Animals↗

Intracellular sodium accumulation during ischemia as the substrate for reperfusion injury.

To elucidate the role of intracellular Na+ kinetics during ischemia and reperfusion in postischemic contractile dysfunction, intracellular Na+ concentration ([Na+]i) was measured in isolated perfused rat hearts using 23Na nuclear magnetic resonance spectroscopy. The extension of the ischemic period from 9 minutes to 15, 21, and 27 minutes (at 37 degrees C) increased [Na+]i at the end of ischemia from 270.0+/-10.4% of preischemic level (mean+/-SE, n=5) to 348.4+/-12.0% (n=5), 491.0+/-34.0% (n=7), and 505.3+/-12.1% (n=5), respectively, whereas the recovery of developed pressure worsened with the prolongation of the ischemic period (95.1+/-4.2%, 84.3+/-1. 2%, 52.8+/-13.7%, and 16.9+/-6.4% of preischemic level). The kinetics of [Na+]i recovery during reperfusion was analyzed by the fitting of a monoexponential function. When the hearts were reperfused with low-[Ca]o (0.15 mmol/L) solution, the time constants of the recovery (tau) after 15-minute (8.07+/-0.85 minutes, n=5) and 21-minute ischemia (6.44+/-0.90, n=5) were significantly extended, with better functional recovery (98.5+/-1.4% for 15-minute [P<0.05]; 98.0+/-1.0% for 21-minute [P<0.05]) compared with standard reperfusion ([Ca]o=2.0 mmol/L, tau=3.58+/-0.28 minutes for 15-minute [P<0.0001]; tau=3.02+/-0.20 for 21-minute [P<0.0001]). A selective inhibitor of Na+/Ca2+ exchanger also decelerated the [Na+]i recovery, which suggests that the recovery reflects the Na+/Ca2+ exchange activity. In contrast, high-[Ca]o reperfusion (5 mmol/L) accelerated the [Na+]i recovery after 9-minute ischemia (tau=2.48+/-0.11 minute, n=5 [P<0.0001]) and 15-minute ischemia (tau=2.10+/-0.07, n=6 [P<0. 05]), but functional recovery deteriorated only in the hearts with 15-minute ischemia (29.8+/-9.4% [P<0.05]). [Na+]i recovery after 27-minute ischemia was incomplete and decelerated by low-[Ca]o reperfusion, with limited improvement of functional recovery (42. 5+/-7.9%, n=5 [P<0.05]). These results indicate that intracellular Na+ accumulation during ischemia is the substrate for reperfusion injury and that the [Na+]i kinetics during reperfusion, which is coupled with Ca2+ influx, also determines the degree of injury.

Animals↗

Genetic polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma.

We have investigated the association between the polymorphisms of drug-metabolizing enzymes and susceptibility to head-and-neck squamous-cell carcinoma (HNSCC). PCR-based analysis was performed on 145 Japanese patients and 164 healthy Japanese controls to determine genotypes of polymorphisms in CYP1A1, CYP2E1, GSTM1, GSTP1, and NAT2. Patients and controls were compared by multivariate analysis. The CYP1A1 Val/Val genotype was seen more frequently in patients than in controls [odds ratio (OR) 4.1, p = 0.038). The frequency of the slow plus intermediate NAT2 genotypes was also higher in patients (OR 2.0, p = 0.039). When we analyzed the distributions of the genotypes in 69 laryngeal and 45 pharyngeal cancer patients, laryngeal cancer patients had a higher frequency of NAT2 slow or intermediate genotype (OR 2.7, p = 0.011) and GSTP1 AA genotype (OR 2.4, p = 0.047) than controls. Pharyngeal cancer patients had a higher frequency of the CYP1A1 Val/Val genotype than controls (OR 5.7, p = 0.034), suggesting that different organs may be responsive to different chemicals from the environment. Furthermore, 23 patients who developed multiple cancers (HNSCC plus other) were compared with 115 patients with HNSCC alone. There was no significant difference in the polymorphisms between the 2 groups, though excessive alcohol consumption (more than 50 g/day of ethanol) appeared to be a risk factor for multiple cancers (p = 0.053).

Aged↗

Comparison between the decrease of dopamine transporter and that of L-DOPA uptake for detection of early to advanced stage of Parkinson's disease in animal models.

Early diagnosis of Parkinson's disease (PD) is important for the potential application of neuroprotective therapies. The purpose of this study was to assess the detection of the early changes of PD by either imaging the dopamine transporter (DAT) or uptake of L-3,4-dihydroxyphenylalanine (L-DOPA). An early to advanced stage model of PD was induced in rats by stereotaxic injection of 1-10 microg 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta. Using adjacent sections of the same animals, the binding of [I-125]beta-CIT, which labels DAT and the uptake of [C-14]L-DOPA, were evaluated 4 weeks after induction of the lesion. Any decrease in dopaminergic neurons was evaluated by in situ hybridization histochemistry (ISH) by detection of DAT mRNA-positive neurons. In addition, the expression levels of DAT, dopa decarboxylase (DDC), and vesicular monoamine transporter (VMAT2) in each neuron were studied with ISH. Our results show a decrease in both [I-125]beta-CIT binding and [C-14]L-DOPA uptake in parallel with a decrease in DA neurons from early to advanced stage models of PD. The decrease in [C-14]L-DOPA uptake was smaller than that in [I-125]beta-CIT binding in the same animal (P < 0.0001). Expression levels of DAT, DDC, and VMAT2 mRNAs were also decreased with the progression of the disease. Although ISH failed to detect the origin of the discrepancy between [I-125]beta-CIT and [C-14]L-DOPA levels, it was concluded that [C-14]L-DOPA levels underestimated the decrease of dopaminergic neurons and that [I-125]beta-CIT levels more precisely reflected the decrease.

Animals↗

Mechanism for abnormal thallium-201 myocardial scintigraphy in patients with left bundle branch block in the absence of angiographic coronary artery disease.

Patients with left bundle branch block (LBBB) often show abnormal images on exercise thallium (T1)-201 scintigraphy without evidence of significant coronary stenosis. We investigated the mechanism for this phenomenon. Six patients with LBBB and without significant coronary stenosis underwent T1-201 SPECT, ECG-gated SPECT imaging with Tc-99m-methoxyisobutyl-isonitrile (MIBI), and atrial pacing stress test. The % count amplitude in Tc-99m-MIBI images was calculated as [(maximal counts) - (minimal counts)]/(minimal counts) x 100. Though all patients had a low count in the septal and inferior wall in T1-201 SPECT images, there was no ischemic production of lactate during an atrial pacing stress test. Nevertheless, gated SPECT images showed attenuated septal activity during systole. In patients with LBBB, the ratios of % count amplitude at the septum to that at the lateral wall at rest (0.47 +/- 0.05, mean +/- SE) were significantly less than the controls (n = 5, 0.83 +/- 0.12, p = 0.014). In conclusion, these results suggest that abnormal T1-201 SPECT images of the septum in patients with LBBB are partially caused by impaired septal wall thickening during systole. Such an abnormal wall motion may reduce blood flow demands to the septum, resulting in reduction of coronary blood flow with little ischemia.

Bundle-Branch Block↗

Technetium-99m HL91 uptake as a tumour hypoxia marker: relationship to tumour blood flow.

Technetium-99m HL91 (HL91) is a potential agent for imaging hypoxic tissue in vivo. To elucidate the relationship between hypoxia and blood flow in a tumour, dual-tracer autoradiography with HL91 and carbon-14 iodoantipyrine (IAP) was performed in a tumour-bearing rat model. The distribution of each tracer was analysed visually and semiquantitatively. In the tumours with central necrotic areas, HL91 uptake was marked around the necrotic areas whereas IAP uptake was marked at the periphery of the tumours, around the areas of marked HL91 uptake. Normalized HL91 uptake (%HL91) was highest in the low normalized IAP uptake (%IAP) fraction in the non-necrotic areas. There was a weak negative correlation between %HL91 and %IAP in the non-necrotic areas (r = -0.322, P<0.0001). In tumours with few or no necrotic areas, HL91 uptake was heterogeneous throughout the tumours, while IAP uptake predominantly occurred at the periphery of the tumours. %HL91 was higher in the inner two-thirds of the tumour than in the outer third. There was again a weak negative correlation between %HL91 and %IAP (r = -0.354, P<0.0001). This study confirmed that high HL91 uptake is related to low blood flow. The marked HL91 uptake around the necrotic region suggests the presence of chronic hypoxia in a tumour.

Animals↗

Correlation of sequential MR images of microsphere-induced cerebral ischemia with histologic changes in rats.

OBJECTIVE: To determine the time course of changes in MRI findings of multiple cerebral microembolism, the authors induced experimental multiple microinfarctions in rats using microspheres and then examined sequential MRI and histopathologic findings. The authors also evaluated how the amount of injected embolic materials affected the findings. METHODS: The authors injected 25-microm microspheres (range, 2000-8000 gm) into the unilateral internal carotid arteries of rats. The animals were assessed by MRI and histopathology at 1 day or 8 days after embolization. RESULTS: One day after embolization, multiple high-intensity areas on T2-weighted images were related to the number of injected microspheres and were associated with regions of cerebral edema on histopathologic specimens. On day 8, the high-intensity areas on T2-weighted images observed on day 1 were markedly diminished in the groups receiving up to 6000 microspheres. In the group injected with 8000 microspheres, however, the high-intensity areas were less diminished, and these areas were significantly larger than in the other groups (P < 0.05). CONCLUSIONS: The MRI features of cerebral ischemia or infarction induced by microsphere embolism vary depending on the number of injected microspheres. Recovery from acute cerebral embolism has a threshold based on ischemic cell volume.

Analysis of Variance↗

Lumped constant for deoxyglucose is decreased when myocardial glucose uptake is enhanced.

Quantification of myocardial glucose uptake by positron emission tomography with [18F]fluorodeoxyglucose (FDG) requires the "lumped constant" (LC), which corrects the difference of affinity between glucose and FDG to glucose transporters and phosphorylating system. Since LC was introduced, it has been considered to be constant. However, this has recently been questioned. To elucidate the constancy of LC by other than radioisotope techniques, the accumulation rate of sugar phosphates (d[SP]/dt) was measured in isolated, perfused rat hearts by 31P NMR spectroscopy with 2-deoxyglucose (DG). We postulate alpha as the affinity of DG to transporters and the phosphorylating system relative to that of glucose. Theoretically, alpha is equivalent to LC. We determined alpha by measuring d[SP]/dt at DG concentration ([DG]) = 10, 7, 5, and 3 mmol/l, keeping the total of glucose concentration ([glucose]) and [DG] to 10 mmol/l. When the glucose uptake was enhanced by insulin (10 mU/ml) or stunning, calculated alpha was reduced (insulin stimulated, 0.15; stunning, 0.19) compared with the control (0.59). These results indicate that LC can be evaluated by methods without radiolabeled tracers and is smaller when glucose uptake is augmented.

Animals↗

Feasibility of fluorodeoxyglucose dual-head gamma camera coincidence imaging in the evaluation of lung cancer: comparison with FDG PET.

UNLABELLED: The purpose of this study was to elucidate the feasibility of fluorodeoxyglucose gamma camera coincidence imaging (FDG GCI) in the evaluation of lung cancer in comparison with FDG PET. METHODS: Twenty-three patients with recently diagnosed lung cancer were examined with both FDG PET and FDG GCI on the same day. Pulmonary lesions were analyzed visually and semiquantitatively using the ratio of lesion-to-background counts (L/B ratio). The L/B ratio of FDG PET without attenuation correction (AC) was also calculated and compared. Nodal stations were only visually analyzed. RESULTS: FDG GCI and FDG PET could detect 22 and 23, respectively, of 23 pulmonary lesions by visual analysis (95.7% versus 100%). The L/B ratio of FDG GCI was 4.26 +/- 2.55, and significantly lower than that of FDG PET (9.29 +/- 4.95; P < 0.01). The L/B ratio of FDG PET was significantly higher with AC than that without AC (9.29 +/- 4.95 vs. 6.66 +/- 4.65; P < 0.01). When the L/B ratio threshold was set at 5.0 for FDG PET and 2.7 for FDG GCI, their sensitivity was 87.0% and 73.9%, respectively. Of the 3 and 6 patients with false-negative results on semiquantitative analysis, the lesions in 3 patients on FDG PET and 4 patients on FDG GCI were less than or equal to 2.0 cm in greatest diameter, respectively. In the assessment of mediastinal involvement, FDG PET was 77.8% sensitive, 78.6% specific and 78.3% accurate, whereas FDG GCI was 77.8% sensitive, 92.9% specific and 87.0% accurate. In the hilar regions, FDG PET was 100% sensitive, 84.2% specific and 87.0% accurate, whereas FDG GCI was 75.0% sensitive, 89.5% specific and 87.0% accurate. CONCLUSION: In this study, FDG GCI yielded results comparable to FDG PET on visual analysis to detect pulmonary lesions and lymph node metastases. However, the lesion-to-background contrasts of pulmonary lesions and nodal involvement were lower in FDG GCI than in FDG PET. Comparison between the L/B ratio of FDG PET with and without AC indicated that, with AC, FDG GCI would be closer to FDG PET in the evaluation of lung cancer.

Adenocarcinoma↗

Applicability of 99mTc-HL91, a putative hypoxic tracer, to detection of tumor hypoxia.

UNLABELLED: To elucidate the applicability of 99mTc-HL91 (HL91) a putative hypoxic tracer, to the imaging of hypoxia in tumors, a biodistribution study of the tracer was performed. The intratumoral distribution of HL91 was compared with that of 14C-deoxyglucose (DG) and the expression of glucose transporter 1 (GLUT1) in an implanted tumor. METHODS: Biodistribution of HL91 after intravenous injection into Wistar rats with rat mammary tumor (Walker-256) was studied by determining blood and tissue levels of radioactivity from 15 min to 6 h after injection. Dual ex vivo autoradiography was performed on sections of the tumor using HL91 (74 MBq) and DG (185 kBq). The same sections were immunohistologically analyzed with anti-GLUT1 antibody. Tumor tissue was histologically divided into areas of viable cancer cells, necrosis and granulation tissue. The viable cancer cell area was further divided into normoxic and hypoxic areas. Uptake of both tracers in each area was measured quantitatively. The intensity of GLUT1 staining (relative optical density [ROD]) in each area was evaluated by densitometry. RESULTS: The uptake of HL91 in the tumor reached a maximal value (0.897 +/- 0.118% ID [injected dose], mean +/- SD, n = 5) at 120 min after intravenous injection of HL91, then gradually decreased. The tumor-to-muscle ratio continued to increase until 360 min (4.34 at 120 min, 7.01 at 240 min and 10.4 at 360 min). HL91 accumulated to significantly higher levels in the hypoxic area than those in the other tissues (P < 0.0001). Uptake of DG and expression of GLUT1 were significantly higher in the hypoxic area than in the normoxic area (P < 0.0001). In the viable cancer cell area, uptake of HL91 and expression of GLUT1 were strongly correlated (r = 0.624-0.868, mean r = 0.743, P < 0.0001), and DG uptake was moderately correlated with GLUT1 expression (r = 0.328-0.669, mean r = 0.505, P < 0.0001). CONCLUSION: These results indicate that HL91 can be used to detect tumor hypoxia.

Animals↗

Comparison of dual-head coincidence gamma camera FDG imaging with FDG PET in detection of breast cancer and axillary lymph node metastasis.

UNLABELLED: Dual-head coincidence gamma camera 18F-fluorodeoxyglucose (FDG) imaging was compared with FDG PET in the detection of breast cancer and axillary lymph node metastasis. METHODS: Both coincidence gamma camera FDG imaging and FDG PET were performed in a cylindrical phantom containing spheres of different sizes and activity ratios (5:1, 10:1 and 15:1) and in 30 women (age range 32-78 y) with suspected breast cancer. Biopsies or mastectomies were performed in all patients. Images were visually assessed, and the count ratio between tumor and normal tissue (T/N ratio) was calculated. RESULTS: In the phantom studies, coincidence gamma camera imaging visualized the smallest sphere (1.0 cm) at a ratio of 15:1 but not at ratios of 5:1 and 10:1. Coincidence gamma camera imaging visualized the other spheres (> or =1.3 cm) at all ratios. PET visualized all spheres at all ratios. In the clinical studies, 22 of 26 breast carcinomas detected by PET were also detected by coincidence gamma camera imaging.. Coincidence gamma camera imaging detected all of the carcinomas > or =2 cm in diameter (n = 10) and 12 of 16 carcinomas <2 cm. In breast carcinomas detected by both PET and coincidence gamma camera imaging, the T/N ratio in non-attenuation-corrected PET (7.12 +/- 7.13) was significantly higher than in coincidence gamma camera imaging (2.90 +/- 1.47, P < 0.005). Four of 8 axillary lymph node metastases detected by PET were detected by coincidence gamma camera imaging. Of 9 axillary lymph node metastases <1.0 cm in diameter, 7 and 3 were detected by PET and coincidence gamma camera imaging, respectively. CONCLUSION: Coincidence gamma camera imaging is useful in detecting breast carcinoma > or =2 cm in diameter but is not reliable for breast carcinoma <2 cm in diameter. Coincidence gamma camera imaging may be useless or even dangerous in the detection of axillary lymph node metastasis.

Adult↗

Validity of 18F-fluorodeoxyglucose imaging with a dual-head coincidence gamma camera for detection of myocardial viability.

UNLABELLED: This study investigated the validity of myocardial 18F-fluorodeoxyglucose (FDG) imaging with a dual-head gamma camera operated in coincidence detection mode (DCD-I) by comparing this technique with conventional PET and SPECT with ultra-high-energy general-purpose collimators (UHGPs). METHODS: The subjects included 5 healthy volunteers and 20 patients with a history of myocardial infarction. FDG (370 MBq) was injected intravenously after 75-g oral glucose loading, and PET, UHGP SPECT and DCD-I were performed 45, 60 and 210 min, respectively, after the injection. The target-to-background ratio of each imaging method was evaluated for the healthy volunteers by comparing myocardial uptake with uptake in the upper lungs or left ventricular cavity. Agreement between the results of the various imaging methods was investigated for the myocardial infarction patients, as was the validity of DCD-I for assessing myocardial viability as judged by comparison with myocardial perfusion SPECT. The left ventricular wall was divided into 18 regions, and uptake was evaluated using a five-grade defect score (0 = normal; 1-3 = low uptake; 4 = defect). RESULTS: The mean ratio of myocardial counts to lung counts was lower on the DCD images (2.77 +/- 1.12) than on the UHGP SPECT images (3.69 +/- 0.98) (P < 0.05). In contrast, the mean ratio of myocardial counts to left ventricular cavity counts was higher on the DCD images (2.76 +/- 1.36) than on the UHGP SPECT images (1.98 +/- 0.70) (P < 0.05). For the patients, only 30.6% of the defect scores obtained by DCD-I agreed with the scores obtained by PET, and the defect scores in the inferior and septal walls were higher for the DCD images than for the PET images. When DCD-I was compared with PET without attenuation correction (AC), agreement improved to 58.3%. When corrected by a modified AC method, DCD-I improved to 48.1%. Agreement between UHGP SPECT and PET was 55.0%. Of the segments (64) for which the defect score of the myocardial perfusion image was greater than that for the FDG PET image, DCD-I without AC, DCD-I with AC and UHGP SPECT allowed an accurate diagnosis in 12 (18.8%), 31 (48.4%) and 43 (67.2%), respectively. CONCLUSION: The image quality of DCD-I is superior to that of UHGP SPECT. However, because the effect of attenuation is marked, accurate AC, by the transmission method, for example, is required to equal the validity of PET.

Female↗

Estimation of shunt flow in coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin.

The shunt flow from the coronary artery to pulmonary arteries was evaluated in 6 patients with coronary-pulmonary fistula by lung perfusion scintigraphy with technetium-99m macroaggregated albumin. In 2 patients, whose degree of visualization of pulmonary arteries by coronary angiography was relatively high, lung perfusion scintigrams demonstrated the defects at the distal of coronary-pulmonary fistulas.

Aged↗

Metabolic changes in hibernating myocardium after percutaneous transluminal coronary angioplasty and the relation between recovery in left ventricular function and free fatty acid metabolism.

To elucidate the changes in oxidative metabolism in hibernating myocardium after coronary revascularization, we performed myocardial single-photon emission computed tomography with a free fatty acid analog, I-123 beta-methyliodophenylpentadecanoic acid (BMIPP), and thallium-201 before and 1 month after percutaneous transluminal coronary angioplasty (PTCA) in 11 patients with angina pectoris caused by single artery stenosis. All patients had improvement in wall motion after PTCA at the region with coronary stenosis; the wall motion abnormality score evaluated by left ventriculography decreased from 5.5+/-0.8 (mean +/- SE) to 2.1+/-0.9, p <0.01) after PTCA. The defect score of I-123 BMIPP images was significantly larger than that of thallium-201 images either before (14+/-1.3 vs 8.9+/-1.1, p <0.01) or 1 month after (7.4+/-1.5 vs 3.7+/-0.8, p <0.01) PTCA. The decrease in the defect score of both images was significant (p <0.01). Changes in the wall motion abnormality score showed a significant correlation with both the change in the defect score of thallium-201 images (r = 0.58, p < 0.01) and that of I-123 BMIPP images (r = 0.75, p <0.01). These results indicate that the metabolism of free fatty acid is impaired in hibernating myocardium, and that improvement in left ventricular function after successful PTCA is strongly associated with the recovery of oxidative metabolism.

Adult↗

Alteration of intracellular Na+ during ischemia in diabetic rat hearts: the role of reduced activity in Na+/H+ exchange against stunning.

To elucidate the contribution of reduced activity of Na+/H+ exchange in streptozotocin-induced diabetic hearts against stunning, intracellular Na+ concentration ([Na+]i) was measured in isolated rat hearts using 23Na-MRS. The recovery of left ventricular developed pressure in hearts reperfused after 15 min global ischaemia at 37 degreesC was significantly better in diabetic ones (102.9+/-2.0% of pre-ischemic level, mean+/-s.e., n=6; P<0.05), and non-diabetic ones pre-treated with potent Na+/H+ exchange inhibitor, EIPA (1 mu mol/l; 93.8+/-2.3%, n=5; *P<0.05) than non-treated, non-diabetic hearts (75.1+/-2.5%, n=8). When diabetic hearts were pre-treated with EIPA, the recovery (101.2+/-2.6%, n=5) was identical to that of non-treated, diabetic hearts. [Na+]i in non-diabetic hearts increased to 329.1+/-8.1% of pre-ischemic level during 15 min ischemia, whereas the increase in [Na+]i in diabetic hearts significantly suppressed to 199.8+/-10.3% (P<0.001). EIPA attenuated the increase of [Na+]i during ischemia to 189.1+/-9.0% in non-diabetic hearts ( P<0.001) and to 155.3+/-4.6% in diabetic hearts (P<0.05). Thus, the EIPA-dependent Na+ accumulation during ischemia, i.e. Na+ influx probably mostly via Na+/H+ exchange was smaller in diabetic hearts by 69.7% compared with that in non-diabetic hearts. These results indicate that the cardiac protection against stunning in streptozotocin-induced diabetic hearts is mediated by the attenuation of Na+ accumulation during ischemia, which is caused by the reduced activity in Na+/H+ exchanger.

Adenosine Triphosphate↗