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Biomedical subjects

Isao Kondo

Publications and source records attributed to Isao Kondo.

15 recordsLinked to original sources

Ultrasonic integrated backscatter discloses intramyocardial hemorrhage in patients with acute myocardial infarction.

BACKGROUND: It has been reported that intramyocardial hemorrhage (IH) can be detected by magnetic resonance imaging (MRI) and IH correlates with the poor prognosis of acute myocardial infarction (AMI). We examined whether integrated backscatter (IBS) can disclose IH in patients with AMI. We recorded IBS images in 34 patients with AMI who underwent coronary angioplasty within 12 hours of symptom onset. METHODS: We measured calibrated IBS (C-IB) and cyclic variation (CV) in the center of the risk area on the third day after reperfusion. C-IB was calculated as: average IBS value of risk area--average IBS value of intraventricular blood. MRI was performed within 3 days after reperfusion. Regional wall motion score index (RWMSI) was calculated as follows: sum of scores (0 - 4) in risk area/number of segments of risk area. We evaluated left ventricular function using RWMSI shortly and one month after reperfusion. RESULTS: RWMSI in the IH group (12 cases) was significantly higher than in the non-IH group (2.3+/-0.5 vs. 1.8+/-0.6: P<0.01) one month later, while RWMSI in both groups was almost the same shortly after reperfusion. The IH group showed a significantly higher value of C-IB than the non-IH group (18.6+/-2.0 vs. 16.0+/-1.4: P<0.01), while there were no significant differences in CV values between two groups. Using 17 as a cutoff value of C-IB, C-IB can detect IH with 92% sensitivity and 91% specificity. Using both CV and C-IB, however, IH can be detected more specifically. CONCLUSION: Ultrasonic IBS, especially C-IB, discloses intramyocardial hemorrhage in patients with reperfused AMI.

Aged↗

Coronary flow reserve by contrast enhanced transesophageal coronary sinus Doppler measurements can evaluate diabetic microvascular dysfunction.

BACKGROUND: This study was undertaken to investigate whether coronary flow reserve (CFR) using coronary sinus flow (CSF), which can be measured by transesophageal Doppler echocardiography (TEDE), especially when contrast enhanced, is useful in evaluating microvascular dysfunction in patients with diabetes mellitus (DM). METHODS AND RESULTS: CSF recordings using contrast enhanced TEDE were performed before and after adenosine triphosphate infusion (0.15 mg x kg(-1) x min(-1)) in 16 patients with type 2 DM and diabetic retinopathy and in 13 non-DM patients (control). Coronary angiography revealed normal epicardial coronary arteries. CFR was defined as the ratio of the antegrade flow velocity time integral in hyperemic conditions and basal levels. Clear envelopes of CSF were obtained in all DM patients using contrast-enhanced TEDE. CFR using CSF in the DM group was significantly decreased compared with the control group (1.4+/-0.4 vs 2.1+/-0.5, p<0.01), but there were no significant differences of age, ejection fraction, rate of hypertension and hypercholesterolemia between the 2 groups. Using 1.7 of CFR as the cut-off value, diabetic microvascular dysfunction could be detected with 82% sensitivity and 83% specificity. CONCLUSIONS: CFR calculated by CSF using contrast-enhanced TEDE may be useful for evaluating diabetic microvascular dysfunction.

Aged↗

Treatment of ischemic limbs based on local recruitment of vascular endothelial growth factor-producing inflammatory cells with ultrasonic microbubble destruction.

OBJECTIVES: We sought to clarify the mechanism for neovascularization by ultrasonic microbubble destruction (US/MB) and its ability to improve the function of ischemic limbs. BACKGROUND: In tissue, US/MB can cause capillary rupture, leading to angiogenesis and arteriogenesis. METHODS: Seven days after removal of the femoral artery (day 0) in mice, microbubble/ultrasound treatment was performed by intermittent insonation (1.6 MHz, mechanical index 1.1) to the ischemic limbs after intravenous infusion of phospholipid-stabilized microbubbles BR14 (US/MB group). Effects were compared with those in untreated mice with ischemic limbs (control group). RESULTS: Immunostaining of the treated muscles revealed a greater leukocyte (CD45-positive cell) count in the US/MB group on days 3 and 7. These cells included F4/80-positive cells (macrophages) and CD3-positive cells (T-lymphocytes), both of which were immunoreactive to vascular endothelial growth factor (VEGF) antibody. Muscular VEGF content by Western blotting was elevated in the US/MB group on day 3, which declined but remained greater until day 21. The US/MB group showed a greater capillary density by alkaline phosphatase stain on day 7 without further increase at day 21. Surface vascularity of the muscles and blood flow were greater in the US/MB group on day 7, which further increased by day 21. Moreover, the US/MB group showed a two-fold longer treadmill time compared with the untreated control group on day 21. None of these favorable effects were observed in mice treated with ultrasound only or microbubbles only. CONCLUSIONS: Ultrasonic destruction of microbubbles delivered to the ischemic limbs can recruit inflammatory cells producing VEGF, which is followed by neovascularization and functional improvement, and thus has a therapeutic potential.

Animals↗

Experimental autoimmune uveitis induced by immunization with retinal pigment epithelium-specific 65-kDa protein peptides.

PURPOSE: To investigate the pathogenic potential and sites of retinal pigment epithelium-specific 65-kDa protein (RPE65) for inducing experimental autoimmune uveitis (EAU) in Lewis rats. METHODS: Twenty-six peptides were chemically synthesized based on the amino acid sequences of human RPE65. These peptides spanned the entire RPE65 sequence. Each peptide was injected into a footpad and the peritoneum of Lewis rats. The eyes were examined by slit-lamp biomicroscopy, and the findings were correlated with the histological findings. The serum antibody titer and lymphocyte reactivity against each peptide was also determined by enzyme-liked immunosorbent assay (ELISA) and lymphocyte proliferation assay, respectively. RESULTS: Active immunization of rats resulted in the induction of EAU with 14 (3 severe and 11 mild) of the 26 peptides. The clinical course of the EAU was similar to that induced by the injection of retinal antigens such as S-antigen or inter-photoreceptor retinoid binding protein (IRBP). However, the histopathologic changes differed from the EAU induced by these retinal antigens. The inflammation was induced mainly from the retinal pigment epithelium (RPE) and the choroid, while the retina was relatively well-preserved except for some granulomatous changes adjacent to the RPE. CONCLUSIONS: Active immunization with peptides making up RPE65 will induce EAU. RPE65 has multiple EAU-inducing sites for Lewis rats.

Animals↗

Treatment of acute myocardial infarction by hepatocyte growth factor gene transfer: the first demonstration of myocardial transfer of a "functional" gene using ultrasonic microbubble destruction.

OBJECTIVES: We examined whether ultrasonic microbubble destruction (US/MB) enables therapeutic myocardial gene transfer of hepatocyte growth factor (HGF) for acute myocardial infarction (MI). BACKGROUND: Hepatocyte growth factor gene transfer provides cardioprotective effects in MI, which requires direct intramyocardial injection or special vectors. Although US/MB was used in myocardial gene transfer, its feasibility in transfer of a therapeutic gene with non-viral vector remains unknown. METHODS: In a rat model of acute MI, naked plasmid (pVaxl) encoding human HGF (1,500 microg) was infused into the left ventricular (LV) chamber during US/MB (HGF-US/MB) or insonation only (HGF-US) or alone (HGF-alone), while control MI rats received empty pVaxl during US/MB (pVaxl-US/MB). For US/MB, transthoracic intermittent insonation with a diagnostic transducer (1.3 MHz) was performed for 2 min at a peak negative pressure of -2,160 kPa during intravenous 20% Optison. RESULTS: Baseline risk area was comparable among the groups. Immunohistology seven days after treatment revealed significant myocardial expression of HGF protein only in HGF-US/MB. At three weeks, LV weight in HGF-US/MB (0.89 +/- 0.03 g) was significantly lower than those in HGF-alone (1.09 +/- 0.08 g), HGF-US (1.04 +/- 0.07 g), and pVaxl-US/MB (1.04 +/- 0.05 g). Moreover, scar size was significantly smaller (16 +/- 6% vs. 39 +/- 5%, 41 +/- 6%, and 40 +/- 4% of total myocardial circumferential length, respectively), while capillary density (49 +/- 8 vs. 34 +/- 5, 37 +/- 6, and 36 +/- 4 capillaries/high-power field, respectively) and arterial density (37 +/- 7 vs. 15 +/- 9, 18 +/- 4, and 14 +/- 11 arterioles/high-power field, respectively) in the risk area were higher in HGF-US/MB than the other groups. CONCLUSIONS: Ultrasound-mediated microbubble destruction may enable myocardial HGF gene transfer with systemic administration of naked plasmid, which enhances angiogenesis, limits infarction size, and prevents LV remodeling after MI.

Animals↗

Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model.

BACKGROUND: Repetitive endomyocardial biopsies are necessary to monitor the effects of immunosuppressants after cardiac transplantation. Contrast ultrasound with microbubble targeting of leukocytes detects acute leukocyte infiltration. We examined whether leukocyte-targeted myocardial contrast echocardiography (MCE) could provide for the quantitative assessment of acute cardiac rejection. METHODS AND RESULTS: Hearts from Brown Norway rats or Lewis rats were transplanted into other Brown Norway rats. Isografts and groups of allografts either untreated or treated with cyclosporin A (CsA) at a low dose (3 mg x kg(-1) x d(-1)) or high dose (10 mg x kg(-1) x d(-1)) from 3 days before transplantation were compared at posttransplantation day 3. Echocardiography-derived left ventricular wall thickening was comparable among the 4 groups. Myocardial blood flow assessed with MCE, relating pulsing intervals with signal intensity (SI), was slightly decreased only in untreated allografts. However, myocardial SI (in gray levels) obtained after a 10-minute period allowing microbubble-leukocyte interactions after contrast injection exhibited a clear gradient in these groups (12+/-2 in untreated allografts, 9+/-5 in allografts treated with low-dose CsA, 6+/-3 in allografts treated with high-dose CsA, and 2+/-1 in isografts, P<0.001). The pattern of difference in SI among the groups agreed well with that in ED-1-positive cell (macrophage) count (25+/-7, 12+/-4, 5+/-3, and 1+/-0 cells per high-power field, respectively, P<0.001), which correlated with CD3-positive cell (T lymphocyte) count (33+/-5, 22+/-5, 9+/-4, and 1+/-0 cells per high-power field, respectively, P<0.001). CONCLUSIONS: Leukocyte-targeted MCE can noninvasively assess the degree of rejection in transplanted hearts by directly revealing the magnitude of intramyocardial infiltration of macrophages and T lymphocytes.

Acute Disease↗

Interaction with leukocytes: phospholipid-stabilized versus albumin-shell microbubbles.

PURPOSE: To confirm that BR14 microbubbles (MBs) can be phagocytosed by activated leukocytes, to determine their stability after phagocytosis, and to evaluate how such characteristics influence the fate of neutrophils containing MBs after insonation. MATERIALS AND METHODS: BR14 and human albumin MBs (2 x 10(7)/mL) were incubated with activated human neutrophils (2 x 10(6)/mL) to allow phagocytosis. Deflation rate of the phagocytosed MBs after pulsed insonation (one burst per second for 5 seconds) at 1.8 MHz with peak negative pressure of -540 kPa or -1,340 kPa, lactate dehydrogenase (LDH) leakage, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain-positive cell count after insonation were compared between the two agents. RESULTS: At -540 kPa, phagocytosed MBs remained nearly unchanged for both agents after insonation. At -1,340 kPa, although human albumin MBs were disrupted on the first or second burst, BR14 MBs remained undisrupted. After -540-kPa insonation, a similar number of apoptotic cells appeared in neutrophils containing human albumin and BR14 MBs. At -540 kPa, LDH leakage was limited in human albumin MBs and BR14 MBs. At -1,340 kPa, LDH leakage was significantly increased in human albumin MBs and BR14 MBs (P <.01, both vs -540 kPa). Apoptotic cells were significantly decreased in human albumin MBs and BR14 MBs (P <.01, both vs -540 kPa). LDH leakage was lower and apoptotic cell count was greater in BR14 MB-containing neutrophils than in human albumin MB-containing neutrophils (both P <.01). CONCLUSION: Compared with human albumin MBs, BR14 MBs were more stable after phagocytosis with insonation. This stability is associated with less disruption and greater induction of apoptosis in leukocytes after relatively high-pressure insonation in the range for diagnostic use.

Adult↗

Quantitative assessment of coronary stenosis by harmonic power Doppler with a simple pulsing sequence and vasodilator stress in patients.

OBJECTIVES: We examined whether myocardial contrast echocardiography (MCE) with harmonic power Doppler (HPD) employing a simple ultrasound pulsing sequence enables estimation of the severity of coronary artery stenosis in patients. BACKGROUND: Contrast intensity (CI) during MCE with intravenous microbubble infusion is dependent on the myocardial blood flow velocity (MBFV) and pulsing interval (PI). METHODS: Based on an in vitro experiment, we devised the MBFV index calculated as the reciprocal of the magnitude of CI decay produced by abrupt PI shortening during intermittent imaging. In 68 coronary artery territories from 49 patients, myocardial HPD images were acquired during intravenous infusion of Levovist, while the long PI with 1:10 electrocardiographic gating was shortened to 1:1, both at baseline and during adenosine triphosphate infusion. The MBFV index in each coronary territory and MBFV reserve as the ratio between hyperemia and baseline were compared with the severity of corresponding coronary artery stenosis assessed by quantitative coronary angiography (QCA) or by pressure guide wire as the fractional flow reserve (FFR). RESULTS: Both the MCE-derived MBFV index during hyperemia and MBFV reserve exhibited significant negative correlations with the QCA-derived stenosis severity (r = -0.56 and r = -0.64, respectively). The MBFV reserve positively correlated with FFR (r = 0.89). By combining the cutoff values of the MBFV index during hyperemia and MBFV reserve, > or =75% of stenoses defined by QCA were determined, with a sensitivity of 77.3%, specificity of 93.4%, and accuracy of 88.3%. CONCLUSIONS: Shortening of PI during intravenous MCE with intermittent HPD imaging under vasodilator stress enables assessment of coronary artery stenoses in patients.

Adult↗

Assessment of right ventricular perfusion after right coronary artery occlusion by myocardial contrast echocardiography.

OBJECTIVES: The purpose of this study was to examine the ability of myocardial contrast echocardiography (MCE) to assess right ventricular (RV) perfusion. BACKGROUND: Although MCE can readily assess left ventricular perfusion abnormalities, there are no data regarding the ability to assess RV perfusion abnormalities. METHODS: The right coronary artery (RCA) was occluded in 10 open-chest dogs. Myocardial contrast echocardiography was performed with 0.27 g/min Levovist infusion by harmonic power Doppler with electrocardiographically gated intermittent triggered imaging at pulsing intervals ranging from 1:1 to 1:20 at baseline and 90 min after RCA occlusion. Video-intensity of the RV wall was plotted against pulsing intervals and was fitted to an exponential function: y = A(1-exp(-bt)), where A is the plateau video-intensity and b is the rate of video-intensity rise. Myocardial contrast echocardiography and microsphere-derived myocardial blood flow (MBF) measurements were performed at baseline and 90 min after RCA occlusion. RESULTS: Because the severity of RV perfusion abnormalities assessed by MBF varied during RCA occlusion, diverse grades of patchy opacification defects were observed by MCE. The RV wall thickness decreased, and the RV dimension increased, after RCA occlusion in each dog. The correlation of occlusion to baseline MBF ratios in the RV wall was closer to the ratio of b (r = 0.897, p = 0.0004) than A (r = 0.767, p = 0.0097) and was the closest to the ratio of Axb (r = 0.935, p < 0.0001). CONCLUSIONS: The RCA occlusion is manifested by RV wall thinning and dilation as well as by perfusion abnormalities consisting of patchy opacification defects by MCE. Myocardial contrast echocardiography-derived refilling parameters can be applied to assess RV perfusion abnormalities produced by RCA occlusion.

Animals↗

Potentiation of C-type natriuretic peptide with ultrasound and microbubbles to prevent neointimal formation after vascular injury in rats.

OBJECTIVES: Long-term intravenous infusion of high-dose C-type natriuretic peptide (CNP) is known to prevent neointimal formation after vascular injury. Ultrasound (US) irradiation during microbubbles (MBs) infusion (US/MBs) has been used for local delivery of bioactive agents. We examined whether short-term infusion of CNP could also inhibit neointimal development and whether combined US/MBs treatment at the beginning of the CNP infusion could enhance its effect. METHODS: In the rat carotid artery-balloon injury model, the intima/media area (I/M) ratio 14 days after injury was compared among various short-term post-injury treatments. For combined US/MBs, a commercial echocardiograph (1.8 MHz, mechanical index 1.0) and albumin-coated octafluoropropane gas MBs were used. RESULTS: Infusion of high-dose CNP (1.0 microg/kg/min) immediately after injury for only 24 h successfully reduced the I/M ratio (0.18+/-0.05) to 18% of the ratio in control rats (1.00+/-0.13) that underwent only balloon injury. Although low-dose CNP (0.1 microg/kg/min for 24 h) alone was not effective in reducing the I/M ratio (0.83+/-0.18), combined US/MBs treatment for the first 80 min of the infusion markedly reduced the I/M ratio (0.17+/-0.07), which persisted until 28 days after injury (0.16+/-0.04). CONCLUSIONS: The effects of CNP on the events occurring early after arterial injury may be important in preventing subsequent neointimal development. Thus, intravenous infusion of CNP with US/MBs at its initiation may provide a clinically feasible anti-restenosis therapy applicable immediately after vascular interventions.

Analysis of Variance↗

Effect of microbubble fragility on transit rate measurement by contrast echography.

We sought to propose a simplified method to measure flow velocity based on ultrasonic microbubble destruction, and investigated the effect of microbubble shell fragility on such measurement. Acoustic density (AD) from the second harmonic short axis image of flow was obtained at variable velocities (2 to 73 mm/s) in an in vitro model during long (1000 ms) and short (33 ms) interval ultrasound (US) pulsing, allowing complete and partial microbubble replenishment between pulses, respectively. Microbubbles with shell elastic modulus of 0.4 MPa and 16 MPa were tested. By shortening pulsing interval, AD diminished gradually, rather than abruptly, to a plateau level for both microbubbles. The extent of AD decay was greater for the fragile than the strong microbubbles. A linear relationship existed between the magnitude of AD decay and flow velocity only in the higher and lower velocity range for the fragile and the strong microbubbles, respectively. Thus, difference in contrast intensities during long and short pulsing intervals, respectively, allowing complete and partial replenishment may provide for velocity measurement, in which choice of optimal microbubble fragility for the range of velocity to measure may increase the accuracy.

Capsules↗

Correlation of functional and structural alterations of the coronary arterioles during development of type II diabetes mellitus in rats.

OBJECTIVE: Cardiac complications in diabetes mellitus (DM) are frequently ascribed to microangiopathy. Therefore, we sought to directly correlate the serial changes in coronary arterial function with the extent of coronary arteriolar remodeling in a model spontaneously developing type II DM. METHODS: Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control Long-Evans Tokushima Otsuka (LETO) rats were used. At 5, 15 and 30 weeks of age, ten rats in each group were subjected to systemic and coronary hemodynamic measurements using the colored microsphere technique before and during maximal coronary hyperemia and histological assessment with Azan-Mallory stain of the coronary arterioles. RESULTS: As early as 15 weeks of age, at which time fasting plasma glucose concentration remained normal, OLETF rats exhibited a lower coronary flow reserve and a greater coronary vascular resistance during hyperemia than did LETO rats. On histomorphometry, OLETF rats exhibited a greater wall-to-lumen ratio and a greater degree of perivascular fibrosis of arterioles at 15 weeks of age and thereafter, both of which exhibited a significant correlation with the minimal coronary vascular resistance. CONCLUSIONS: The degree of functional deterioration in coronary circulation was directly correlated with the severity of coronary arteriolar structural remodeling during the development of microangiopathy in early stage of DM.

Animals↗

Myocardial blood flow measurements in rats with simple pulsing contrast echocardiography.

Relationship between contrast intensity and ultrasound (US) pulsing interval has been utilized to quantify myocardial blood flow (MBF) during myocardial contrast echocardiography (MCE). We tested if an MCE method employing a simple pulsing sequence during intravenous contrast infusion has the ability to quantify MBF in rats. We performed MCE in 17 rats using a 5- to 12-MHz broadband transducer during microbubble infusion via the femoral vein. Acoustic density (AD) from the anterior wall of the left ventricle imaged in the short axis plane was plotted against the frame number after shortening the pulsing interval (PI) from 1:20 to 1:1 end-systolic ECG gating. The relation between AD and frame number was fitted to a decay function. The rate of the AD decay was decreased during dipyridamole infusion, but was increased by causing coronary stenosis. The AD during long PI imaging remained unchanged during the interventions. Estimated MBF by MCE after correction by heart rate exhibited a close correlation (r = 0.83) with the present "gold standard" of colored microsphere-derived MBF. Thus, the decay rate of the contrast intensity obtained with the high-frequency transducer after abrupt shortening of PI during intravenous microbubble infusion may provide for noninvasive measurement of MBF in rats.

Animals↗

Assessment of myocardial viability in prior myocardial infarction by intravenous bolus microbubble injection: a new time domain index to estimate regional relative myocardial blood volume.

We tested whether the duration of myocardial opacification by harmonic power Doppler imaging after intravenous bolus microbubble injection (with a definition of "the end of opacification") would reflect the remaining vascular bed in infarcted segments. In 28 patients with previous myocardial infarction and 20 control patients, we performed harmonic power Doppler imaging after intravenous bolus injection of 1.5 g of Levovist. Using multiframe trigger mode in which 4 consecutive frames were imaged at every sixth end systole, which formed 1 "burst," we recorded anterior/septal and inferior/posterior walls separately on the center of each apical view with individual boluses. The duration of segmental opacification was measured as the number of "bursts" in which color signals persisted until the fourth frame. The duration was similar between the anterior/septal and inferior/posterior walls (13 +/- 3 vs 13 +/- 3 bursts, not significant) in the control group. In myocardial infarction patients, the duration was significantly shorter in the infarcted than in the control segments (6 +/- 6 vs 14 +/- 3 bursts, P < .001) and their ratio and difference exhibited significant correlations (r = 0.82, P < .001 and r = 0.91, P < .001, respectively) with the activity ratio on thallium Tl 201 single-photon emission computed tomography at rest. Thus, the duration of opacification by harmonic power Doppler imaging after intravenous bolus microbubble injection, the measurement of which was standardized by using multiframe trigger mode, may be useful in assessing regional myocardial viability in patients with previous myocardial infarction.

Aged↗

Inhibition of migration and proliferation of rat vascular smooth muscle cells by a new HMG-CoA reductase inhibitor, pitavastatin.

The migration and proliferation of vascular smooth muscle cells (SMCs) are known to play roles in the pathogenesis of atherosclerosis. Therapy with a reductase inhibitor of 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) ("statin") produces significant alterations in various SMC functions. The objectives of the present study were to determine whether pitavastatin, a new chemically synthesized and powerful statin, can affect angiotensin II (Ang II)- and platelet-derived growth factor (PDGF)-induced migration and proliferation of cultured rat vascular SMCs. The effect of pitavastatin on cell viability was also examined in these cells. Migration was evaluated by the Boyden's chamber method using microchemotaxis chambers. As expected, Ang II and PDGF BB potently stimulated cell migration in a concentration-dependent manner. Pitavastatin significantly inhibited Ang II (10(-6) mol/l)-induced migration at the concentrations of 10(-8) and 10(-7) mol/l. Pitavastatin also inhibited PDGF BB (1 ng/ml)-induced migration at concentrations between 10(-9) and 10(-8) mol/l in a relatively concentration-dependent manner. This statin modestly but significantly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced DNA synthesis at concentrations between 10(-9) and 10(-7) mol/l. In addition, pitavastatin clearly inhibited Ang II (10(-6) mol/l)- and PDGF BB (1 ng/ml)-induced increases of cell number at concentrations between 10(-9) and 10(-7) mol/l. Pitavastatin did not affect lactate dehydrogenase release from these cells at the concentrations used in this experiment. In a trypan blue exclusion test, dead cells stained with trypan blue were not found 24 h after treatment with 10(-9), 10(-8) or 10(-7) mol/l of pitavastatin. These findings suggest that pitavastatin suppresses the migration and proliferation stimulated by Ang II and PDGF BB without affecting cell viability. Pitavastatin may exert an anti-atherogenic effect, in part, through these mechanisms.

Animals↗