Heterogeneity of resting and hyperemic myocardial blood flow in healthy humans.
(73/980)
OBJECTIVE: Absolute myocardial blood flow (MBF) is not well-defined in large normal populations, and appears to be heterogeneous in both humans and animals. These factors contribute to the difficulties in defining resting MBF to hibernating myocardium. We therefore assessed absolute baseline and hyperemic MBF in a large population of normal humans. METHODS: MBF was quantified by positron emission tomography with oxygen-15-labeled water at baseline and during hyperemia induced by either adenosine or dipyridamole in 131 men and 38 women, aged 21-86 (mean 46+/-12) years. MBF was corrected for workload using the rate-pressure product (RPP). RESULTS: Uncorrected baseline MBF ranged from 0.590 to 2.050 (mean 0.985+/-0.230) ml/min/g (coefficient of variation=27%), and corrected MBF from 0.736 to 2.428 (mean 1.330+/-0.316) ml/min/g (coefficient of variation=24%). MBF in the inferior region was significantly (P<0.0001) lower than either the anterior or lateral regions. Baseline MBF in females was significantly (P<0.001) higher than in males. CONCLUSIONS: These results confirm the heterogeneity of MBF in normals and highlight the difficulty in establishing the lower limit of normal MBF. (+info)
Antiplatelet agents in tissue factor-induced blood coagulation.
(74/980)
Several platelet inhibitors were examined in a tissue factor (TF)-initiated model of whole blood coagulation. In vitro coagulation of human blood from normal donors was initiated by 25 pM TF while contact pathway coagulation was suppressed using corn trypsin inhibitor. Products of the reaction were analyzed by immunoassay. Preactivation of platelets with the thrombin receptor activation peptide did not influence significantly the clotting time or thrombin-antithrombin III complex (TAT) formation. Addition of prostaglandin E(1) (5 microM) caused a significant delay in clotting (10.0 minutes) versus control (4.3 minutes). The prolonged clotting time is correlated with delays in platelet activation, formation of TAT, and fibrinopeptide A (FPA) release. In blood from subjects receiving acetylsalicylic acid (ASA or aspirin), none of the measured products of coagulation were significantly affected. Similarly, no significant effect was observed when 5 microM dipyridamole (Persantine) was added to the blood. Antagonists of the platelet integrin receptor glycoprotein (gp) IIb/IIIa had intermediate effects on the reaction. A 1- to 2-minute delay in clot time and FPA formation was observed with addition of the antibodies 7E3 and Reopro (abciximab) (10 microg/mL), accompanied by a 40% to 70% reduction in the maximal rate of TAT formation and delay in platelet activation. The cyclic heptapetide, Integrilin (eptifibatide), at 5 microM concentration slightly prolonged clot time and significantly attenuated the maximum rate of TAT formation. The disruption of the gpIIb/IIIa-ligand interaction not only affects platelet aggregation, but also decreases the rate of TF-initiated thrombin generation in whole blood, demonstrating a potent antithrombotic effect superimposed on the antiaggregation characteristics. (+info)
Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT.
(75/980)
OBJECTIVE: To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients. DESIGN: Cohort study. SETTING: Regional cardiothoracic unit. PATIENTS: 49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress. MAIN OUTCOME MEASURES: Regional myocardial perfusion by SPECT, performed with (99m)Tc tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity. RESULTS: Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wall, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images. CONCLUSIONS: Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects. (+info)
Neonatal thrombocytosis resulting from the maternal use of non-narcotic antischizophrenic drugs during pregnancy.
(76/980)
Neonatal thrombocytosis can result from maternal narcotic drug abuse. The case of a male infant is reported who was born to a woman with schizophrenia treated with non-narcotic psychotropic drugs during pregnancy; he developed severe prolonged thrombocytosis. The platelet count reached 1310 x 10(9)/l on day 15. This thrombocytosis persisted for three months. The patient was treated with dipyridamole. A bone marrow aspirate showed normal myeloid and erythroid precursors with an increased number of megakaryocytes. Plasma concentrations of interleukin 6 and thrombopoietin were suppressed. No obvious complications from the thrombocytosis occurred, and the platelet count fell to within the upper limit of normal after 3 months of age. This case indicates that thrombocytosis may occur in infants born to mothers treated with non-narcotic psychopharmaceutical drugs during pregnancy. The thrombocytosis in this case may have been induced by factors other than interleukin 6 or thrombopoietin. (+info)
Reproducibility of an automatic quantitation of regional myocardial wall motion and systolic thickening on gated 99mTc-sestamibi myocardial SPECT.
(77/980)
We investigated the reproducibility of an automatic quantitative algorithm for measuring regional myocardial wall motion and systolic thickening. METHODS: 99mTc-sestamibi gated myocardial SPECT with dipyridamole stress was performed twice consecutively on 31 patients with known or suspected coronary artery disease, with the patients in the same position for each scan. With AutoQUANT software, segmental wall motion and systolic thickening were quantified automatically and expressed in millimeters and percentage increase, respectively, for 20 segments. Afterward, the correlation and agreement between repeated measurements were investigated, and the influences of wall location, perfusion grade, and partitioning of the myocardium on reproducibility were evaluated by ANOVA and t testing. RESULTS: High correlations (r = 0.95 for wall motion and 0.88 for systolic thickening) and good agreements (weighted kappa = 0.81 and 0.71, respectively) were obtained from repeated measurements on consecutive gated SPECT. Changes in wall location and perfusion grade did not cause significant differences between repeated measurements (P > 0.05 in ANOVA and t testing), but a change in partitioning did. On Bland-Altman analysis, 2 SDs for repeated wall motion and for systolic thickening were 2.0 mm and 20%, respectively. CONCLUSION: The automatic quantitative algorithm for myocardial SPECT provided by AutoQUANT software has good reproducibility under diverse conditions. A change of motion > 2.0 mm or a change of systolic thickening > 20% can be regarded as significant during a follow-up study using this software. (+info)
Comparison of sestamibi, tetrofosmin, and Q12 retention in porcine myocardium.
(78/980)
Although there are several 99mTc perfusion tracers introduced for clinical use, there are no data available directly comparing these tracers with microsphere-determined flow. The aim of this study was to compare the myocardial retention of sestamibi, tetrofosmin, and Q12 in a porcine model. METHODS: We used a pig model with (n = 6) or without (n = 3) coronary occlusion. Each pig received a simultaneous injection of sestamibi and either tetrofosmin (group 1, n = 5) or Q12 (group 2, n = 4) labeled with either 99mTc or 95mTc (physical half-life, 61 d; photon energy, 204 keV) during pharmacologic vasodilation. Absolute myocardial retention of each tracer was calculated from the myocardial tracer activity and arterial input function. RESULTS: The plot of all three tracers versus flow achieved a plateau at a higher flow range. However, sestamibi showed a higher mean retention than either tetrofosmin (group 1, 0.27 +/- 0.11 vs. 0.16 +/- 0.06 mL/g/min, respectively; P < 0.01) or Q12 (group 2, 0.32 +/- 0.13 vs. 0.09 +/- 0.03 mL/g/min, respectively; P < 0.01). Furthermore, when a linear regression analysis was performed to assess the relationship between retention and microsphere-determined flow, sestamibi showed a greater increment in retention than did tetrofosmin or Q12. CONCLUSION: Although all of the tracers showed a nonlinear increase in retention as flow increased, sestamibi may display more favorable characteristics as a flow tracer in the porcine heart. (+info)
Assessment of myocardial perfusion in coronary artery disease by magnetic resonance: a comparison with positron emission tomography and coronary angiography.
(79/980)
BACKGROUND: Monitoring contrast medium wash-in kinetics in hyperemic myocardium by magnetic resonance (MR) allows for the detection of stenosed coronary arteries. In this prospective study, the quality of a multislice MR approach with respect to the detection and sizing of compromised myocardium was determined and compared with positron emission tomography (PET) and quantitative coronary angiography. METHODS AND RESULTS: A total of 48 patients and healthy subjects were studied by MR using a multislice hybrid echo-planar pulse sequence for monitoring the myocardial first pass kinetics of gadolinium-diethylenetriamine pentaacetic acid bismethylamide (Omniscan; 0.1 mmol/kg injected at 3 mL/s IV) during hyperemia (dipyridamole 0.56 mg/kg). Signal intensity upslope as a measure of myocardial perfusion was calculated in 32 sectors per heart from pixelwise parametric maps in the subendocardial layer and for full wall thickness. Before coronary angiography, coronary flow reserve (hyperemia induced by dipyridamole 0.56 mg/kg) was determined in corresponding sectors by (13)N-ammonia PET. Receiver-operator characteristic analysis of subendocardial upslope data revealed a sensitivity and specificity of 91% and 94%, respectively, for the detection of coronary artery disease as defined by PET (mean coronary flow reserve minus 2SD of controls) and a sensitivity and specificity of 87% and 85%, respectively, in comparison with quantitative coronary angiography (diameter stenosis >/=50%). The number of pathological sectors per patient on PET and MR studies correlated linearly (slope, 0.94; r=0.76; P<0.0001). CONCLUSIONS: The presented MR approach reliably identifies patients with coronary artery stenoses and provides information on the amount of compromised myocardium, even when perfusion abnormalities are confined to the subendocardial layer. This modality may qualify for its clinical application in the management of coronary artery disease. (+info)
Dipyridamole inhibits human peritoneal mesothelial cell proliferation in vitro and attenuates rat peritoneal fibrosis in vivo.
(80/980)
BACKGROUND: Peritoneal fibrosis (PF) is one of the most serious complications after long-term continuous ambulatory peritoneal dialysis (CAPD). Proliferation of human peritoneal mesothelial cells (HPMC) and matrix over-production are regarded as the main processes predisposing to PF. Dipyridamole (DP) has been reported to have potential as an antiproliferative and antifibrotic agent. We thus investigated the effect of DP in inhibiting proliferation and collagen synthesis of HPMC. A rat model of peritonitis-induced PF was also established to demonstrate the in vivo preventive effect of DP. METHODS: HPMC was cultured from human omentum by an enzyme digestion METHOD: Cell proliferation was measured by the methyltetrazolium assay. Intracellular cAMP was measured using an enzyme immunoassay (EIA) kit. Total collagen synthesis was measured by (3)H-proline incorporation assay. Expression of collagen alpha1 (I) and collagen alpha 1 (III) mRNAs was determined by Northern blotting. The rat model of peritonitis-induced PF was developed by adding dextran microbeads (Cytodex, 8 mg/1 mL volume) to a standardized suspension (3 x 10(9)) of Staphylococcus aureus. DP was administrated via intravenous infusion (4 mg in 1 h) daily for seven days. Macroscopic grading of intraperitoneal adhesions and histological analyses of peritoneal thickness and collagen expression were performed. RESULTS: Addition of DP to HPMC cultures suppressed serum-stimulated cell proliferation and collagen synthesis. The antimitogenic and antifibrotic effects of DP appear to be predominantly mediated through the cAMP pathway, as DP increased intracellular cAMP in a dose-dependent manner. The macroscopic grade of intraperitoneal adhesion and peritoneal thickness were both significantly increased in animals treated with Cytodex plus S. aureus; on the other hand, DP attenuated these fibrotic changes with statistical significance (P < 0.01). Analysis of gene expression of collagen alpha 1 (I) and alpha1 (III) in the peritoneal tissue of experimental animals yielded similar results. CONCLUSIONS: This study suggests that dipyridamole may have therapeutic potential in treating peritoneal fibrosis. (+info)