Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation.

OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-ß) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-ß signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-ß expression and Smad2/3 following TGF-ß phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-ß expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.

Controlling joint instability delays the degeneration of articular cartilage in a rat model.

OBJECTIVE: Joint instability induced by anterior cruciate ligament (ACL) transection is commonly considered as a predisposing factor for osteoarthritis (OA) of the knee; however, the influence of re-stabilization on the protection of articular cartilage is unclear. The aim of this study was to evaluate the effect of joint re-stabilization on articular cartilage using an instability and re-stabilization ACL transection model. DESIGN: To induce different models of joint instability, our laboratory created a controlled abnormal joint movement (CAJM) group and an anterior cruciate ligament transection group (ACL-T). Seventy-five Wistar male rats were randomly assigned to the CAJM (n = 30), ACL-T (n = 30), or no treatment (INTACT) group (n = 15). Cartilage changes were assessed with soft X-ray analysis, histological and immunohistochemistry analysis, and real-time polymerase chain reaction (PCR) analysis at 2, 4, and 12 weeks. RESULTS: Joint instability, as indicated by the difference in anterior displacement between the CAJM and ACL-T groups (P < 0.001), and cartilage degeneration, as evaluated according to the Osteoarthritis Research Society International (OARSI) score, were significantly higher in the ACL-T group than the CAJM group at 12 weeks (P < 0.001). Moreover, joint re-stabilization maintained cartilage structure (thickness [P < 0.001], surface roughness [P < 0.001], and glycosaminoglycan stainability [P < 0.001]) and suppressed tumor necrosis factor-alpha (TNF-α) and caspase-3 at 4 weeks after surgery. CONCLUSION: Re-stabilization of joint instability may suppress inflammatory cytokines, thereby delaying the progression of OA. Joint instability is a substantial contributor to cartilage degeneration.

Chiral magnetic soliton lattice on a chiral helimagnet.

Using Lorenz microscopy and small-angle electron diffraction, we directly present that the chiral magnetic soliton lattice (CSL) continuously evolves from a chiral helimagnetic structure in small magnetic fields in Cr(1/3)NbS2. An incommensurate CSL undergoes a phase transition to a commensurate ferromagnetic state at the critical field strength. The period of a CSL, which exerts an effective potential for itinerant spins, is tuned by simply changing the field strength. Chiral magnetic orders observed do not exhibit any structural dislocation, indicating their high stability and robustness in Cr(1/3)NbS2.

Electron microscopy at a sub-50 pm resolution.

An aberration-corrected electron microscope developed in CREST project has been applied for imaging atoms and clusters buried inside crystals. The resolution of the microscope in scanning transmission electron microscopy (STEM) has experimentally proved to be better than 47 pm by use of a cold-field emission gun at 300 kV. The high resolution has given an advantage for imaging light elements such as lithium atoms discriminating one by one. Moreover, a three-dimensional structure imaging has been demonstrated for dopant clusters by a sub-50 pm STEM, using its high depth resolution.

Measurement method of aberration from Ronchigram by autocorrelation function.

Aberrations up to the fifth-order were successfully measured using an autocorrelation function of the segmental areas of a Ronchigram. The method applied to aberration measurement in a newly developed 300kV microscope that is equipped with a spherical aberration corrector for probe-forming systems. The experimental Ronchigram agreed well with the simulated Ronchigram that was calculated by using the measured aberrations. The Ronchigram had an infinite magnification area with a half-angle of 50mrad, corresponding to the convergence angle of a uniform phase.

Expression of polymorphonuclear leukocyte adhesion molecules and its clinical significance in patients treated with percutaneous transluminal coronary angioplasty.

OBJECTIVES: This study evaluated the role of neutrophil adhesion molecules LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18) and p150,95 (CD11c/CD18) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Several recent studies have suggested that cell adhesion molecules on both neutrophils and vascular endothelial cells play an important role in the process of tissue inflammation. METHODS: Thirty-eight patients (30 men, 8 women; mean [+/-SE] age 56 +/- 5 years, range 38 to 76) with single-vessel coronary artery disease of the left anterior descending artery underwent coronary angioplasty. Peripheral blood was sampled at baseline before, immediately after and 12, 24, 48 and 144 h after PTCA. The expression of CD18, CD11a, CD11b and CD11c on the surface of polymorphonuclear leukocytes was examined by flow cytometry with monoclonal antibodies. RESULTS: In patients without subsequent restenosis, there was no change in mean channel fluorescence intensity (MFI) of CD18 at each sampling time. However, in the patients with restenosis, the MFI of CD18 significantly increased at 48 h after PTCA (from 57 +/- 6 to 73 +/- 8, p = 0.0008). The MFI of CD11b increased slightly at 48 h after PTCA in patients without restenosis (from 584 +/- 121 to 735 +/- 114, p = 0.037). In patients with restenosis, the MFI of CD11b was slightly increased at 24 h after PTCA (from 586 +/- 122 to 768 +/- 214, p = 0.018) and significantly increased at 48 h after PTCA (to 1,534 +/- 268, p = 0.0006). The expression of CD11a and CD11c did not change at any sampling points after PTCA in either of the two patient groups. Percent change in the expression of CD18 at 48 h after PTCA (from baseline) and that of CD11b were correlated (r = 0.73, p = 0.0008) in patients with restenosis. CONCLUSIONS: Inflammatory stimuli within the coronary vessels associated with coronary angioplasty may upregulate Mac-1 expression on the surface of polymorphonuclear leukocytes. This process may be more marked in patients who experience later restenosis. Thus, activation of neutrophil adhesion molecule Mac-1 at 48 h after PTCA may have value as a predictor of subsequent restenosis.

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease.

OBJECTIVES: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). BACKGROUND: Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. METHODS: Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. RESULTS: The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). CONCLUSIONS: Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.

Antibody against oxidized low density lipoprotein may predict progression or regression of atherosclerotic coronary artery disease.

OBJECTIVES: This study aimed to elucidate whether an antibody against oxidized low density lipoprotein (anti-Ox-LDL) could predict short-term coronary artery atherosclerotic lesion progression. BACKGROUND: It is still controversial whether higher levels of the anti-Ox-LDL titer are associated with atherosclerotic coronary artery disease. METHODS: In 52 patients undergoing coronary angioplasty and six-month follow-up angiography, we performed quantitative coronary angiographic analysis of a lesion on a branch away from the intervention site vessel and assessed lesion progression or regression using the Progression-Regression score calculated as the baseline minimal lumen diameter minus the follow-up minimal lumen diameter. The serum anti-Ox-LDL titer was measured using an enzyme-linked immunosorbent assay method just before the initial angiography in all patients. RESULTS: The anti-Ox-LDL titer was 16.6+/-1.5 AcU/ml in the progression group (Progression-Regression score >0.15 mm; n = 20), which was significantly higher (p < 0.001) than the value of 9.5+/-1.2 in the regression group (< or =-0.15 mm; n = 14) and also higher (p < 0.01) than the value of 11.4+/-1.3 in the no-change group (-0.15 to 0.15 mm; n = 18). The Progression-Regression score was correlated with the antibody titer in all patients (r = 0.56, p < 0.001). Multiple regression analysis showed that the Progression-Regression score was independently correlated with the antibody titer (r = 0.44, p < 0.01) as well as lipoprotein (a) (r = 0.33, p < 0.05). CONCLUSIONS: Anti-Ox-LDL may be an independent predictor of coronary atherosclerotic lesion progression in the short term.

Difference in HMG1-induced DNA bending among microsatellites.

Sequence-dependency of high-mobility group protein (HMG) 1-induced DNA bending is examined for microsatellites using a circularization assay which can measure the extent of bending. Fragments of 133 bp containing (GGA/TCC)11 in the middle showed greater bending than those harboring (GAA/TTC)11 and (GT/AC)17 repeats, and fragments possessing (GA/TC)17 exhibited only slight bending. Differences were not detected for fragments having the repeats near the end. Filter binding assays showed no difference in their binding affinity, suggesting that GGA/TCC repeats are more flexible than the other three repeats as concerns HMG1-induced bending. These results suggest that the mammalian genomes comprise flexible and inflexible regions of microsatellites which might play roles in chromatin architectures and in dynamic packaging of genomic DNA during the cell division cycle.

Serum prostaglandin D synthase level after coronary angioplasty may predict occurrence of restenosis.

Lipocalin-type prostaglandin D synthase (L-PGDS), which is responsible for the biosynthesis of PGD2, has recently been found to be present in the atherosclerotic plaque of the human coronary artery and also to be secreted in human serum. We measured the serum L-PGDS level and compared it with the expressions of the platelet membrane surface glycoprotein and neutrophil adhesion molecule in patients undergoing PTCA. The L-PGDS level significantly decreased (P < 0.01) and the platelet surface expression of CD62P (P-selectin) significantly increased (P < 0.01) immediately after PTCA in the coronary sinus blood. Both changes were inversely correlated (R = -0.72, P < 0.001). Although the L-PGDS level in the coronary sinus blood remained equivalent to the baseline level in patients who experienced restenosis, the level increased over the baseline level (P < 0.01) at 48 h after PTCA in patients without restenosis. Neutrophil surface expression of CD11b (alpha subunit of Mac-1) significantly increased at 24 h (P < 0.01) to 48 h (P < 0.001) after PTCA in the coronary sinus blood in patients with restenosis but the change showed less significant in patients without restenosis. The changes in the L-PGDS level and the CD11b expression at 48 h after PTCA were inversely correlated (R = -0.55, P < 0.05). An increased serum L-PGDS level at 48 h after PTCA possibly predicts the avoidance of late restenosis. It is suggested that reduction in PGD2 synthesis triggers platelet activation and that a subsequent increase in the PGD2 synthesis suppresses inflammatory reaction at the intervention site indicated by neutrophil activation and inhibits development of restenosis. Pharmacological or biological intervention that increases endogenous PGD2 synthesis should be tested as a new strategy to prevent restenosis.

Clinical significance of neutrophil adhesion molecules expression after coronary angioplasty on the development of restenosis.

To investigate the neutrophil activation process following percutaneous transluminal coronary angioplasty (PTCA), we examined the expressions of Mac-1 (CD11b/CD18), L-selectin (CD62L), and sialyl-LewisX (SLX) on the surface of neutrophils after the PTCA procedure, by flow cytometric analysis. Twenty-nine patients with single vessel coronary artery disease of the left anterior descending artery who underwent elective PTCA were enrolled. In the 17 patients without restenosis at the follow-up angiography, the mean channel fluorescence intensity (MFI) for CD18, CD62L and SLX did not change after PTCA. Only the CD11b level was increased at 48 h after the PTCA. In the remaining 12 patients who developed restenosis, the MFI values for CD18 and CD11b were increased at 24 h and 48 h after the PTCA. The MFI value for CD62L was decreased and that for SLX was increased at 48 h after the PTCA. These changes were more prominent in the coronary sinus blood samples than in those of the peripheral blood samples. Our data indicate the down-regulation of L-selectin, probably by shedding, as well as the up-regulations of Mac-1 and sialyl-LewisX, especially in patients with restenosis. It is suggested that neutrophil activation by an interaction between the selectin family and carbohydrate ligands after PTCA may play a role in the development of restenosis, as does the integrin family.

Clinical and experimental studies of the effects of atrial extrastimulation and rapid pacing on atrial flutter cycle. Evidence of macro-reentry with an excitable gap.

To investigate the mechanism of atrial flutter in human beings, effects of atrial pacing and extrastimulation on flutter cycle length were studied. In four cases, properly timed extrastimuli shortened the F-F interval after the extrastimulus without affecting the stimulus-encompassing interval. The width of the excitable gap ranged from 14 to 25 percent of the basic flutter cycle length (mean +/- standard deviation 20.4 +/- 4.1). Entrainment to rapid atrial pacing was demonstrated in each case. The width of the entrainment zone nearly coincided with that of the excitable gap in each case. In 16 days, atrial flutter was induced by electrical stimulation after an obstacle was placed between the superior and the inferior venae cavae according to Rosenblueth and Garcia Ramos. In 11 dogs, extrastimuli shortened the F-F interval next to the stimulus-encompassing interval as in the clinical study. The excitable gap, measured in six dogs, ranged from 15 to 24 percent of the basic flutter cycle length (mean 20.6 +/- 3.0). Entrainment was observed in six dogs studied and, during entrainment, the atrial activation sequence was almost the same as that during the basic flutter cycle. It is concluded that shortening of the F-F interval next to the stimulus-encompassing interval that is not affected favors macro-reentry as the mechanism of atrial flutter in human beings.

Activation of the osmoregulated ompF and ompC genes by the OmpR protein in Escherichia coli: a study involving chimeric promoters.

The expression of each of the Escherichia coli ompF and ompC genes is activated by the common positive regulator, OmpR, in response to the medium osmolarity. The promoters for these genes consist of canonical -35 and -10 regions, and upstream OmpR-binding sites. In this study, we constructed a functional ompF-ompC chimeric promoter consisting of the OmpR-binding site of ompF, and the -35 and -10 regions of ompC, which was fused to the lacZ gene on a low-copy-number plasmid. It is known that the ompF and ompC genes are expressed in a different manner in cells with mutations in the ompR gene. In this respect, it was found that the ompF-ompC chimeric promoter behaves just like ompF promoter with respect to an ompR mutation (ompR472). It was revealed that, in this chimeric promoter, the OmpR-binding site must be located stereospecifically with respect to the -35 and -10 regions for OmpR-dependent transcription of the ompF-ompC chimeric promoter to occur. These results are discussed in relation to the structures and functions of the ompF and ompC promoters, the occurrence of a DNA curvature in the promoter regions being implied, which may be an important parameter for the transcription activation by the OmpR protein.

Activation of the osmoregulated ompC gene by the OmpR protein in Escherichia coli: a study involving synthetic OmpR-binding sequences.

Expression of the Escherichia coli outer membrane proteins, OmpC and OmpF, is regulated in response to the medium osmolarity. The OmpR and EnvZ proteins are transcriptional factors involved in this osmotic regulation of the ompC and ompF genes. In particular, expression of the ompC gene is activated by the positive regulator, OmpR, in response to high osmolarity of the medium. In this study, we succeeded in defining a functional OmpR-binding sequence by analyzing a set of synthetic oligonucleotides, and propose a consensus motif for OmpR-binding. It was also demonstrated that the asymmetric OmpR-binding sequence, thus identified, can activate the canonical ompC promoter in an orientation independent-manner, providing that this sequence is placed closely and stereo-specifically with respect to the -35 region.

Expression of micF involved in porin synthesis in Escherichia coli: two distinct cis-acting elements respectively regulate micF expression positively and negatively.

micF RNA, whose sequence is highly complementary to a 5'-portion of ompF mRNA, has been implicated in the osmoregulation and thermoregulation of the ompF porin gene in Escherichia coli. To define and characterize cis-acting regulatory regions upstream of the micF promoter, a series of deletions of the micF promoter fused to the lacZ gene were constructed. Two distinct regions, which function differently, were identified as cis-acting regulatory elements, namely, one responsible for OmpR-dependent activation and the other for OmpR-independent repression of micF expression. The former contains the OmpR-binding site, which simultaneously regulates both the genes, micF and ompC, in response to the medium osmolarity. The latter may be involved in an unknown regulatory process of micF expression.

Transfer of cefoperazone into human skin fluid.

The transfer of cefoperazone into exudates from excoriated skin wounds was studied in 13 adolescent and adult patients. Subjects were given an intravenous bolus injection of 50 mg/kg of body weight. Concentrations of cefoperazone in serum and in exudate fluids were determined by bioassay using Escherichia coli as the test organism. Mean (+/- SD) cefoperazone concentration in serum reached 333.3 +/- 103.3 micrograms/ml 30 minutes after the injection and decreased to 16.4 +/- 5.7 micrograms/ml eight hours after the injection. In exudate fluids, the peak value was 52.7 +/- 22.1 micrograms/ml at one hour. Eight hours after the injection, the mean concentration in the exudate was 10.7 +/- 7.2 micrograms/ml, which was considerably above the minimum inhibitory concentrations for important pathogens.

Skew deviation as a complication of cardiac catheterization.

PURPOSE: To report three patients who developed diplopia and skew deviation after cardiac catheterization. DESIGN: Interventional case series. METHODS: Three patients complained of diplopia after cardiac catheterization for myocardial infarction (two male patients) or aortic dissection (one female patient). Examination demonstrated skew deviation in each patient. RESULTS: Diplopia and skew deviation were mild and resolved completely in 4 months (case 1), 16 months (case 2), and 1.5 months (case 3). Sensitive signs of minor ischemic damage to the brain stem that cause such disorders are not detectable by neuroimaging. CONCLUSION: Rarely, cardiac catheterization may be complicated by diplopia and skew deviation.

Comparison of the Ca2+ entry channels responsible for mechanical responses of guinea-pig aorta to noradrenaline and thapsigargin using SK&F 96365 and LOE 908.

Noradrenaline (NA) produces sustained contractions in conduit arteries such as aorta isolated from various animal species. In guinea-pig aorta, NA-produced sustained contraction is largely dependent upon the influx of extracellular Ca2+, but is refractory to the treatment with organic Ca2+ entry blockers. In the present study, we attempted to characterize pharmacologically the Ca2+ entry channel responsible for NA-produced sustained contraction of guinea-pig aorta using SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenylethyl]-1H-imi dazole) and LOE 908 ((R,S)-(3,4-dihydro-6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl-N,N-di-[2- (2,3,4-trimethoxyphenyl)ethyl]-acetamide), both of which block voltage-independent Ca2+ channels. The effects of SK&F 96365 and LOE 908 on NA-produced contraction were compared with those on extracellular Ca2+-dependent contractile and endothelium-dependent relaxant responses to thapsigargin (TSG), an inhibitor of Ca2+-pump Ca2+-ATPase. NA (3x10(-6) M)-produced sustained contraction of guinea-pig aorta without endothelium exhibited a strong dependency on the extracellular Ca2+. Nicardipine (10(-7) M), diltiazem (10(-5) M) and verapamil (10(-5) M) did not show any appreciable inhibitory effects on NA-produced sustained contraction. SK&F 96365 concentration-dependently (10(-6)-10(-4) M) attenuated the NA-produced sustained contraction whereas LOE 908 did not affect it at concentrations up to 10(-4) M. Similarly, extracellular Ca2+-dependent contraction of guinea-pig aorta without endothelium in response to TSG was also diminished by SK&F 96365 but was unaffected by LOE 908. In fura-PE3-loaded vascular preparations, SK&F 96365 decreased both cytoplasmic Ca2+ level ([Ca2+]i) and muscle tension elevated by NA and TSG. Both SK&F 96365 and LOE 908 did not affect an endothelium-dependent relaxation of guinea-pig aorta in response to TSG. These findings suggest that in guinea-pig aortic smooth muscle cells, NA activates Ca2+ influx across the plasma-membrane through the Ca2+-permeable channel which is identical with or has similar properties to the store-operated Ca2+ channel (SOCC) stimulated by TSG, but is distinct from endothelial cell SOCC.

Immunological response to oxidized LDL occurs in association with oxidative DNA damage independently of serum LDL concentrations in dyslipidemic patients.

Oxidative modification of LDL induces immunogenic epitopes in the LDL molecule, and the presence of antibodies against oxidized LDL (anti-Ox-LDL) has been demonstrated in human sera. However, little is known about the clinical significance of anti-Ox-LDL. To elucidate a clinical relationship between the immunological response to oxidized LDL and cellular oxidative stress, we measured serum titers of anti-Ox-LDL in 45 unselected patients with hypercholesterolemia and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), considered a biomarker of the oxidative damage to DNA. The anti-Ox-LDL titer was not correlated with the serum LDL-C concentration, but was correlated with the 8-OHdG concentration (r = 0.300, P < 0.05) in a simple linear regression. Multiple regression analysis indicated that 8-OHdG was independently correlated with anti-Ox-LDL (r = 0.429, P < 0.05), but no other variables, including LDL-C concentrations and smoking habit, were correlated with anti-Ox-LDL. In 16 subgroup patients, the concentrations of TC, TG and LDL-C decreased and the HDL-C concentration increased after cholesterol-lowering therapy with fluvastatin. In addition, both the anti-Ox LDL titer (14.0 +/- 9.5 to 11.4 +/- 6.6 AcU/ml, P < 0.05) and the 8-OHdG concentration (1.19 +/- 0.41 to 0.85 +/- 0.43 ng/ml, P < 0.05) also decreased after fluvastatin therapy. The immunological response to LDL oxidation on vascular wall tissues or cells appear to occur in association with oxidative DNA damage. The measurement of anti-Ox-LDL may be a useful indicator for lipid-lowering therapy.

Relationship of thallium-201 clearance on exercise stress myocardial scintigraphy to coronary flow reserve in patients with coronary artery disease.

OBJECTIVE: We evaluated thallium-201 (201Th) clearance measurement during exercise myocardial scintigraphy in patients with coronary artery disease, for the assessment of coronary circulatory function and diagnosis. DESIGN: The clearance rate of 201Th was compared with the coronary flow reserve measured by Doppler coronary flow velocimetry. METHODS: We selected 20 patients who had chronic stable angina with single-vessel coronary artery disease of the left anterior descending artery (LAD) and underwent percutaneous transluminal coronary angioplasty (PTCA). Ten control patients had atypical chest pain but no detectable heart disease. Regional net clearance of 201Th was measured from the early and delayed bull's-eye images of 201Th exercise stress single photon emission tomography (SPECT). Using a Doppler catheter, we also measured coronary flow reserve of the LAD, which was obtained by the intracoronary administration of papaverine. RESULTS: The net 201Th clearance in the anterior wall myocardium in the patients with coronary artery disease before PTCA was significantly less than that in the controls. At follow-up angiography after successful PTCA, it increased. The coronary flow reserve before PTCA was also lower than that in the controls. It was increased immediately after PTCA, and was more markedly increased at the follow-up angiography. Before PTCA, regional net clearance in the anterior myocardium was correlated with the coronary flow reserve of the LAD. The ratio for the net clearance of the anterior myocardium at follow-up angiography to that before PTCA was also correlated with the ratio for coronary flow reserve. CONCLUSIONS: In patients with coronary artery disease, the regional 201Th clearance in the ischaemic area measured by exercise 201Th SPECT is correlated with the coronary flow reserve of the affected artery. Moreover, the increase in the clearance rate after PTCA is also correlated with that in the coronary flow reserve. Thus the measurement of regional 201Th clearance might be a useful non-invasive method of estimating of the coronary flow reserve.