Junko Sano

Clinical significance of increased plasma concentration of macrophage colony–stimulating factor in patients with angina pectoris

OBJECTIVES To determine the effect of macrophage colony-stimulating factor (MCSF) on atherogenesis in patients with coronary artery disease (CAD), we assessed the relation between the plasma concentration of MCSF and the incidence of acute coronary events in patients with CAD. BACKGROUND Cytokines such as MCSF play a central role in inflammatory and proliferative responses in patients with acute coronary syndromes. However, the effect of MCSF on the clinical course in patients with CAD is still not known. METHODS We measured the plasma MCSF concentration in 142 patients with documented CAD (62 +/- 9 years) and followed up for a mean period of 14 +/- 6 months. The study included 97 patients with stable angina (SA), 45 patients with unstable angina (UA) and 22 age-matched control subjects. The predictors of coronary events were analyzed by using a Cox proportional hazards model. RESULTS The mean plasma MCSF concentration in patients with UA was significantly higher than that in patients with SA and in control subjects (981 +/- 277 vs. 693 +/- 223 vs. 680 +/- 158 pg/ml, p < 0.001). The mean plasma MCSF concentration in the 20 patients with coronary events was significantly higher than that in patients without coronary events (1,192 +/- 232 vs. 690 +/- 213 pg/ml, p < 0.001). The predictors of unfavorable outcome were an increased MCSF concentration, the presence of CAD and a low ejection fraction. CONCLUSIONS These findings suggest that an increased circulating MCSF concentration reflects atherosclerotic progression in patients with CAD and predicts future cardiac events.

Simultaneous assessment of Tc-99m-sestamibi and I-123-BMIPP myocardial distribution in patients with myocardial infarction: evaluation of left ventricular function with ECG-gated myocardial SPECT.

Abstract123I-labeled 15-(p-iodophenyl)-3R,S-methyl pentadecanoic acid (BMIPP) is a branched-chain free fatty acid that is used to evaluate various cardiac diseases. The aim of the present study was to investigate the relationship between myocardial perfusion (99mTc-sestamibi) and BMIPP uptake, and to correlate perfusion and metabolic alterations with regional left ventricular dysfunction in patients with myocardial infarction (MI). ECG-gated dual-isotope myocardial SPECT was performed on 130 patients with MI with sestamibi (555 MBq) and BMIPP (148 MBq). The patients were classified into 3 groups according to PTCA therapy and the interval between the onset of infarction and RI injection (OR time). Group A (n-56) included patients whose OR time was less than one month and who had undergone successful PTCA, Group B (n=36) had OR times of less than one month and had conservative medical therapy, and Group C (n=38) had OR times of over one month. The severity scores of the dual-isotope images were calculated from the defect scores in 9 segments. From the ECG-gated SPECT data with sestamibi, the left ventricular ejection fraction (LVEF; %) and regional wall motion were determined automatically using the QGS programTM. LVEF obtained from gated SPECT correlated well with the severity scores for sestamibi and BMIPP (r=−0.68 and −0.76, respectively). The Δ severity scores (BMIPP scores — sestamibi scores) of Group A were significantly higher than those of the other two groups (3.6±3.0 vs. 1.5±1.7 and 1.0±1.4, p<0.001). The rate of dysfunctional segments with normal sestamibi distribution was significantly higher in Group A than in Group C (20.7% vs. 6.7%, p<0.001). ECG-gated dual-isotope SPECT is useful since myocardial perfusion, fatty acid metabolism and left ventricular function can be analyzed during a single examination, so that this procedure has the potential to provide comprehensive information when evaluating patients with ischemic heart disease.

Rapid data acquisition protocol in ECG-gated myocardial perfusion SPECT with Tc-99m-tetrofosmin

Into 25 patients with heart disorders,99mTc-tetrofosmin 555–740 MBq was injected intravenously at rest. After 40 minutes, ECG-gated myocardial perfusion SPECT was performed with a two detector gamma camera VERTEX (ADAC), setting up two detectors to form a 90-degree angle. Sixteen frames per R-R interval were acquired during a 180° rotation from the RAO 45° to the LPO 45°. A pair of data sets with standard (SDA) and rapid data acquisition (RDA) protocols was collected. In an SDA protocol, SPECT imaging was performed for 50 sec per step in 5° angular steps (total acquisition time; 15 minutes). An RDA protocol was conducted with 12 sec per step, 6° angular steps (acquisition time, 3 minutes). LVEF (%) and LVEDVml quantitated automatically with a QGS program showed excellent correlations between two protocols with correlation coefficients of 0.980 (p < 0.01) and 0.983 (p < 0.01), respectively. Subsequently visual assessment of regional wall motion based on a four-point grading system was carried out with a 3-D cine LV display. High complete agreement was gained with 158 (90.3%) out of total 175 segments, so that assessment of the global and regional LV function with the RDA protocol demonstrated high reliability and feasibility.

Assessment of contractile response to dobutamine stress by means of ECG-gated myocardial SPECT: Comparison with myocardial perfusion and fatty acid metabolism

The present study assessed left ventricular performance during dobutamine stress measured using gated SPECT, and compared the results to myocardial perfusion and fatty acid metabolism.MethodsThirty-six patients with myocardial infarction given99mTc-sestamibi or99mTc-tetrofosmin were examined by gated SPECT at rest and during dobutamine stress (4-20 µg • kg-1 • min-1). After acquiring data at the highest dose,201T1C1 was injected and dual-isotope SPECT was performed to assess myocardial ischemia. Thirty of 36 patients also underwent myocardial SPECT with123I-BMIPP. Regional wall motion changes during dobutamine infusion were determined from the gated SPECT data and classified as: (1) Improvement, (2) Worsening, (3) No change, and (4) Biphasic response. For myocardial segments of each infarct area, stress201Tl, rest99mTc and123I-BMIPP uptakes were graded on a five-point scoring system of defects from 0 (normal) to 4 (grossly defective).ResultsRest99mTc defect score index (DSI) in No change area was significantly higher than that in Biphasic area. The ΔDSI (stress201T1 – rest99mTc) in Biphasic area was significantly higher than those in Improvement and No change areas. The ΔDSI (BMIPP –99mTc) in Worsening area tended to be higher than that in No Change area.ConclusionsRegional contractile response to dobutamine stress analyzed by gated SPECT showed that the response in-myocardial infarct areas could be classified by rest and stress myocardial perfusion and BMIPP accumulation.

Serial assessment of left ventricular performance at rest and during bicycle exercise by ECG-gated myocardial perfusion SPECT.

The present study evaluates left ventricular performance during exercise by ECG-gated myocardial perfusion SPECT with short-time data collection. Methods: The study population consisted of 10 healthy volunteers (Group N) and 9 patients with ischemic heart disease (Group I). Seven patients in Group I had a history of prior myocardial infarction. Rest ECG-gated SPECT was performed 40 min after an injection of Tc-99m-tetrofosmin (555–740 MBq). After resting data acquisition, Group N underwent up to two 5-min stages of exercise (75 and 125 watts) on a detachable bicycle ergometer. The Group I patients all underwent symptom-limited, maximal testing on the ergometer. ECG-gated SPECT data were acquired from both groups for 3 min at rest and during the last 3 min of each exercise stage. Results: Significant increases occurred in LVEF from rest to peak stress in both groups (from 55.4±5.8 to 66.6±4.1% in group N, p<0.0001; from 49.0±12.8 to 56.7±13.8% in Group I, p<0.001). The LVESV values significantly decreased to peak stress in Group N (from 49.9±13.1 to 37.8±10.0 ml, p<0.0001), whereas LVEDV did not change (from 110.6±18.9 to 112.0±19.0 ml). In contrast, the LVESV values at rest and under peak stress were similar in Group I (from 52.6±23.9 to 51.7±31.4 ml) and LVEDV in Group I at peak exercise tended to increase (from 102.8±36.7 to 111.3±39.0 ml). The changes in LVESV from rest to peak stress were significantly different between Groups N and I (−12.1±6.3 vs.−0.9±11.6 ml, p<0.02). Conclusion: ECG-gated SPECT with short-time data collection can assess left ventricular function during exercise and may offer useful information for evaluating patients with ischemic heart disease.

Are multiple plaque disruptions more common in patients with acute coronary syndrome than in patients with stable ischemic heart disease

Background Plaque disruption with or without thrombus plays a key role in acute ccrcnary syndrome(ACS) and sudden progression of coronary lesions. Previous cur study demonstrated that plaque disruptions in culprit lesion is mere ccmmcn in patients with ACS than stable ischemic heart disease(SIHD). We investigated whether the prevalence of plaque disruptions in non ischemic related arteries is different between in patients with ACS and SIHD in living subjects. Methods We performed coronary angioscopy in non ischemic related artery on coronary angiography in 32 patients with ACS and 30 patients with SIHD. Forty-one arteries were explored in each groups. Results At least one plaque disruption was found somewhere other than on the culprit artery I” 31 patients(50%). Plaque disruption was found mere frequently in ACS group(Zlpts.65.6%) than in SIHD group(lOpts.33.3%)(pcO.O01). Conclusion Multiple plaque disruptions were mere ccmmcn in patients with acute ccrcnary syndrome than in patient with stable ischemic heart disease. These results indicate that acute coronary syndrome is not a local vascular accident but a pancoronary process.

Effect of Dietary Protein on Myocardial Ornithine Decarboxylase Activity in the Rat.

ラットの心筋ODC活性がタンパク質摂取により誘導されるか, またisoproterenol (ISO) 投与刺激によりこの酵素活性が上昇をきたす際に摂取タンパク質が影響を与えるかを検討した。その結果, カゼイン群の心筋ODC活性は, 絶食群, 無タンパク食群, ツェイン食群のそれらに比べ有意に高値であった。ISO投与による心筋ODC活性, 心筋putrescine含量の上昇も, カゼイン摂食群が絶食群と無タンパク食群に比し有意に高値であった。これらの結果から, タンパク質摂取によるODC誘導にはタンパク質の栄養価が高いことが必要であり, また, 交感神経刺激による心筋ODC活性の上昇をも食事タンパク質摂取が修飾することが示された。このことは心臓の成長や病的心肥大におけるタンパク質栄養の関与を示唆するものと考えられる。