Invasive treatment is not superior to conservative treatment in patients with non-Q-wave MI.
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Journal Article↗
Biomedical subjects
S Kaul
Publications and source records attributed to S Kaul.
Effect of vitamin A deficiency on the hydrolysis of retinoyl beta-glucuronide to retinoic acid by rat tissue organelles in vitro.
In keeping with the in vivo observation that the conversion of retinoyl beta-glucuronide (RBG) to retinoic acid (RA) is enhanced in vitamin A-deficient (A-) rats, the relative rates of hydrolysis of RBG to RA by various organelles of liver, kidney and intestine were found to be higher in A- rats than in vitamin A-sufficient (A+) rats (mean ratio 1.28; range 1.05-1.63). The lysosomal fraction of kidney and the microsomal fraction of liver showed the highest ratios for RBG hydrolysis; namely, 1.63 and 1.57, respectively (p < 0.005). The rates of hydrolysis of an ether glucuronide, p-nitrophenyl-beta-D-glucosiduronate (pNPG), were also enhanced in A- rats. The ratios of activities were again highest in kidney lysosomes and in liver microsomes; namely, 1.51 (p < 0.005) and 1.42 (p < 0.05), respectively. The non-ionic detergent, Triton X-100, increased RBG hydrolysis in organelles of A+ (19-27%) more than in those of A- rats (8-14%). The ratios of activities +/- SEM with 0.02% Triton X-100 in organelles of kidney, liver and intestine were 1.25 +/- 0.03, 1.22 +/- 0.03 and 1.24 +/- 0.03 in A+ rats and were 1.11 +/- 0.02, 1.07 +/- 0.02 and 1.13 +/- 0.03, respectively, in A- rats. Thus, Triton X-100 had a significantly greater effect (p < 0.005) on the membranes of A+ rats than on those of A- rats. In conclusion, the increased appearance of RA in the plasma after RBG administration in vivo seems to be caused by enhanced activity of beta-glucuronidases in tissue organelles, augmented in part by better access of the substrate to the membrane-bound enzymes.
Animals↗
Myocardial contrast echocardiography: 15 years of research and development.
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Contrast Media↗
Coronary and myocardial blood volumes: noninvasive tools to assess the coronary microcirculation?
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Animals↗
Detection of coronary artery disease with myocardial contrast echocardiography: comparison with 99mTc-sestamibi single-photon emission computed tomography.
BACKGROUND: The purpose of this study was to determine whether myocardial contrast echocardiography (MCE) can be used to detect coronary artery disease (CAD) during rest and pharmacological stress in humans through the use of venous injections of contrast. METHODS AND RESULTS: Thirty patients with known or suspected CAD underwent MCE and 99mTc-sestamibi single-photon emission computed tomography (SPECT) at baseline and after dipyridamole (0.56 mg x kg(-1)) infusion. Ten myocardial segments (5 each in the apical two- and four-chamber views) from the two sets of images using both methods were scored for myocardial perfusion as follows: 1=normal, 0.5=mildly reduced, and 0=severely reduced. The information from baseline and postdipyridamole images was then used to determine whether an abnormal segment was irreversible (similar abnormal perfusion at baseline and after dipyridamole) or reversible (perfusion better at baseline compared with after dipyridamole). Concordance between segmental scores was 92% (kappa=.99) for both methods. Concordance between normal perfusion and reversible or irreversible segmental defects was 90% (kappa=.80). Agreem between the two methods for each of the three vascular territories in each patient was 90% (kappa=.77), while agreement for the presence or absence of CAD in each patient was 86% (kappa=.86). In the 4 patients with disagreement, the perfusion scores were 0.5 for SPECT and 1.0 for MCE. CONCLUSIONS: This study shows that MCE, with venous injection of contrast, can define the presence of CAD during rest and pharmacological stress. The location of perfusion abnormalities and their physiologic relevance (reversible or irreversible) by MCE is similar to that provided by SPECT. MCE, therefore, holds promise for the noninvasive assessment of myocardial perfusion in humans.
Adult↗
Myocardial perfusion imaging in the setting of coronary artery stenosis and acute myocardial infarction using venous injection of a second-generation echocardiographic contrast agent.
BACKGROUND: We hypothesized that by producing excellent myocardial opacification, venous injection of FS-069 coupled with intermittent harmonic imaging (IHI) can be used to determine the presence and severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. METHODS AND RESULTS: Twelve dogs were imaged both continuously and intermittently (every end systole) in the fundamental (2 MHz) and harmonic (transmit at 2 and receive at 4 MHz) modes. FS-069 (1 mL) was injected intravenously for all stages and modes of imaging. Myocardial video intensity was severalfold (P<.01) higher during IHI than all other modes of imaging. Perfusion defects were difficult to measure during continuous and intermittent fundamental imaging and during continuous harmonic imaging. In comparison, the defects were clearly demarcated during IHI. When this mode was used, the magnitude of perfusion mismatch during hyperemia in the presence of a coronary stenosis correlated closely with the magnitude of flow mismatch when radiolabeled microspheres were used (r=.94). The perfusion defect sizes during coronary occlusion and reperfusion also correlated closely with postmortem risk area (r=.89) and infarct size (r=.96), respectively. CONCLUSIONS: Venous injection of FS-069 coupled with IHI produces excellent myocardial opacification. This approach can be used to determine the severity of coronary stenoses during hyperemia, the size of the risk area during coronary occlusion, and the extent of myocardial salvage after reperfusion. This approach, therefore, holds promise in the clinical setting.
Animals↗
Enhancement of left ventricular cavity opacification by harmonic imaging after venous injection of Albunex.
Venous injection of Albunex does not consistently produce left ventricular (LV) cavity opacification during conventional echocardiography. We postulated that by increasing the signal-to-noise ratio, harmonic imaging will result in more successful LV cavity opacification and provide a better assessment of regional LV systolic function. Forty-two patients with poor baseline endocardial delineation were given 10 ml intravenous injections of Albunex during continuous fundamental and harmonic imaging. Change in segmental wall-thickening scores and the confidence levels for these scores were assessed for 3 observers with various levels of experience. Compared with fundamental imaging, harmonic imaging significantly improved the success of LV cavity opacification (83% vs 62%, p <0.05). The background-subtracted video intensity within the central two thirds of the LV cavity increased threefold (from 10 +/- 15 to 31 +/- 29, p <0.05) with harmonic imaging. The spatial extent of opacification increased from 40% of the LV cavity during fundamental imaging to 65% with harmonic imaging (p <0.001). The confidence level for assessing regional LV systolic function improved (p <0.05) after contrast administration, particularly when observer experience was limited. We conclude that in patients with poor endocardial definition, injection of intravenous Albunex should be combined with harmonic imaging to improve LV cavity opacification.
Albumins↗
Effects of GP IIb/IIIa receptor monoclonal antibody (7E3), heparin, and aspirin in an ex vivo canine arteriovenous shunt model of stent thrombosis.
BACKGROUND: Thrombosis is an important limitation of metallic coronary stents, especially in smaller vessels in which shear rates are high. Monoclonal antibody to platelet glycoprotein IIb/IIIa receptor (7E3) has been shown to inhibit shear-induced platelet aggregation. In this study, we compared the effects of 7E3, heparin, and aspirin on stent thrombosis in an ex vivo arteriovenous shunt model of high-shear blood flow. METHODS AND RESULTS: An ex vivo arteriovenous shunt was created in 10 anesthetized dogs. Control rough-surface slotted-tube nitinol stents (n = 72) expanded to 2 mm in diameter in a tubular perfusion chamber were interposed in the shunt and exposed to flowing arterial blood at a shear rate of 2100s-1 for 20 minutes. The animals were treated with intravenous murine 7E3 (Fab')2 (0.2, 0.4, and 0.8 mg/kg), heparin (100 U/kg), or aspirin (10 mg/kg). Effects of the test agents on thrombus weight, platelet aggregation, platelet P-selectin expression, bleeding time, and activated clotting time (ACT) were quantified. 7E3 reduced stent thrombosis by 95% (20 +/- 1 to 1 +/- 1 mg, P < .001) and platelet aggregation by 94% (14 +/- 2 to 1 +/- 1 omega, P < .001) at the highest dose (0.8 mg/kg). 7E3 significantly prolonged bleeding time but had no effect on ACT and platelet P-selectin expression. Heparin prolonged ACT but had no significant effect on stent thrombosis or platelet aggregation. Aspirin, although it inhibited platelet aggregation by 65%, had no effect on stent thrombosis (19 +/- 2 versus 20 +/- 1 mg in controls). CONCLUSIONS: 7E3 produced a dose-dependent inhibition of acute stent thrombosis under high-shear flow conditions. Stent thrombosis was resistant to heparin and aspirin. Thus, 7E3 may be an effective agent for preventing stent thrombosis.
Abciximab↗
New developments in ultrasound systems for contrast echocardiography.
Contrast echocardiography (CE) has evolved significantly in the past decade. Contrast agents and the hardware and software used to detect them and display optimal images have developed in tandem. Not only are hardware and contrast agents available that allow left ventricular cavity enhancement, but recent research points to the usefulness of CE for the evaluation of myocardial perfusion in the cardiac catheterization laboratory and operating room. Advances in ultrasound technology, such as transient harmonic imaging and integrated backscatter, coupled with the development of newer contrast agents that contain smaller, more stable microbubbles capable of transpulmonary passage for intravenous injection, promise a vast increase in the applications of CE in clinical practice.
Contrast Media↗
Myocardial viability in patients with chronic coronary artery disease and previous myocardial infarction: comparison of myocardial contrast echocardiography and myocardial perfusion scintigraphy.
The aim of this study was to compare perfusion patterns on myocardial contrast echocardiography with those on myocardial perfusion scintigraphy for the assessment of myocardial viability in patients with previous myocardial infarction. Accordingly, perfusion scores with the two techniques were compared in 91 ventricular regions in 21 patients with previous (>6 weeks old) myocardial infarction. Complete concordance between the two techniques was found in 63 (69%) regions; 25 (27%) regions were discordant by only 1 grade, and complete discordance (2 grades) was found in only 3 (3%) regions. A kappa statistic of 0.65 indicated good concordance between the two techniques. Although the scores on both techniques demonstrated a relation with the wall motion score, the correlation between the myocardial contrast echocardiography and wall motion scores was closer (r = -0.63 vs r = -0.50, p = 0.05). It is concluded that myocardial contrast echocardiography provides similar information regarding myocardial viability as myocardial perfusion scintigraphy in patients with coronary artery disease and previous myocardial infarction.
Cell Survival↗
Nuclear factor-kappaB activity and arterial response to balloon injury.
We studied the effect of arterial balloon injury on nuclear factor-kappaB (NF-kappaB) mobilization and ICAM-1 expression in untreated rats and rats treated with aspirin. Baseline NF-kappaB nuclear binding in smooth muscle cells (SMC) increased two-fold within 6 h after balloon injury. The binding returned to baseline 3 days after injury. Consistently nuclear staining of p65 active subunit increased in the medial SMC following balloon injury. There was no baseline ICAM-1 expression. Within 3 days after balloon injury there was marked medial ICAM-1 expression, that localized to neointima 7 days after injury and to regrowing endothelial cells 14 days after injury. Treatment with aspirin inhibited NF-kappaB nuclear translocation and binding and was associated with reduction of ICAM-1 expression, SMC proliferation and neointimal thickening following balloon injury. These data suggest that transient mobilization of NF-kappaB in vascular SMC after balloon injury mediates ICAM-1 expression and is involved in arterial response to balloon injury.
Animals↗
Deoxygenated blood minimizes adherence of sonicated albumin microbubbles during cardioplegic arrest and after blood reperfusion: experimental and clinical observations with myocardial contrast echocardiography.
Both administration of cardioplegic solution and blood reperfusion result in endothelial dysfunction. The transit rate of albumin microbubbles during myocardial contrast echocardiography may reflect endothelial injury. Accordingly, we performed myocardial contrast echocardiography in 12 dogs undergoing cardiopulmonary bypass and measured the myocardial transit rate of microbubbles injected into the aortic root during delivery of cardioplegic solutions containing arterial and venous blood and delivery of pure crystalloid cardioplegic solution. The myocardial transit rate of 99mTc-labeled red blood cells was measured and perfusates were sampled for biochemical analysis at each stage. The microbubble transit rate was markedly prolonged during delivery of crystalloid cardioplegic solution and improved significantly during infusion of blood cardioplegic solution (p < 0.001); venous compared with arterial blood in the solution resulted in a greater rate (p < 0.001). The microbubble transit rate did not correlate with pH, oxygen tension or carbon dioxide tension values, or K+ concentration. The red blood cell transit rate remained constant regardless of the cardioplegic perfusate infused. Myocardial contrast echocardiography was also performed in 12 patients undergoing coronary artery bypass who underwent sequential arterial and venous reperfusion after cardioplegic arrest. The microbubble transit rate was faster with venous than arterial blood reperfusion (p = 0.01), although this gain was diminished when arterial blood reperfusion preceded venous blood reperfusion (p = 0.05). Our results indicate that endothelial dysfunction after cardioplegic arrest may be ameliorated by reperfusion with venous rather than arterial blood.
Albumins↗
Myocardial contrast echocardiography.
MCE has evolved from a laboratory tool to a clinical procedure. It would be wrong to consider it merely another tool for imaging of myocardial perfusion. As discussed, it allows physicians to bring physiology and pathophysiology to the bedside, providing a better understanding of the underlying mechanisms of abnormal findings in individual patients. MCE can provide quantitative measurements that can be repeated as often as necessary in a patient. Because of its complexity, large clinical studies are necessary to define the role of MCE in the general clinical milieu. Advances in MCE continue at a very rapid pace, and its potential for the study of endothelial function, site-specific targeting, and local delivery of drugs appears promising. Its role will continue to evolve into the early part of the next century. What we learn of the myocardium can be easily applied to other organ systems accessible to ultrasound. The future of MCE appears very exciting.
Animals↗
Myocardial contrast echocardiography in acute myocardial infarction using aortic root injections of microbubbles in conjunction with harmonic imaging: potential application in the cardiac catheterization laboratory.
OBJECTIVES: The aim of this study was to evaluate myocardial contrast echocardiography using aortic root injections with harmonic imaging in experimental acute myocardial infarction to determine the potential of this approach in the cardiac catheterization laboratory. BACKGROUND: It would be desirable to have an adjunctive procedure that could evaluate myocardial perfusion at the time of cardiac catheterization in patients with acute myocardial infarction. A single injection of contrast medium in the aortic root would provide complete information on myocardial perfusion in a cross section of the heart. High quality images would provide on-line assessment of myocardial perfusion without recourse to image processing. These data could be very valuable for determining patient management. METHODS: Perfusion defects on myocardial contrast echocardiography were measured during coronary occlusion and reflow, using fundamental and harmonic imaging in both continuous and intermittent modes in nine open chest dogs. These defects were compared with risk area on technetium-99m autoradiography and infarct size on tissue staining. RESULTS: Whereas harmonic imaging increased myocardial video intensity by more than twofold (p < 0.001) compared with fundamental imaging after aortic root injection of contrast medium, intermittent imaging was not superior to continuous imaging. The improved signal to noise ratio of harmonic imaging allowed on-line definition of risk area (r = 0.98) and infarct size (r = 0.93) without recourse to off-line processing. Similar results could be obtained with fundamental imaging only after off-line processing. CONCLUSIONS: Aortic root injection of contrast medium coupled with harmonic imaging can be used to provide accurate on-line assessment of risk area and infarct size during acute myocardial infarction. These results have important implications for the catheterization laboratory.
Adenosine↗
Interactions between microbubbles and ultrasound: in vitro and in vivo observations.
OBJECTIVES: We attempted to examine the interactions between ultrasound and microbubbles. BACKGROUND: The interactions between microbubbles and ultrasound are poorly understood. We hypothesized that 1) ultrasound destroys microbubbles, and 2) this destruction can be minimized by limiting the exposure of microbubbles to ultrasound. METHODS: We performed in vitro and in vivo experiments in which microbubbles were insonated at different frequencies, transmission powers and pulsing intervals. Video intensity decay was measured in vitro and confirmed by measurements of microbubble size and concentrations. Peak video intensity and mean microbubble myocardial transit rates were measured in vivo. RESULTS: Imaging at lower frequencies and higher transmission powers resulted in more rapid video intensity decay (p = 0.01), and decreasing exposure of microbubbles to ultrasound minimized their destruction in vitro. Although these effects were also noted in vivo with venous injections of microbubbles, they were not seen with aortic root or direct coronary artery injections. CONCLUSIONS: Ultrasound results in microbubble destruction that is more evident at lower frequencies and higher acoustic powers. Reducing the exposure of microbubbles to ultrasound minimizes their destruction. This effect is most marked in vivo with venous rather than aortic or direct coronary injections of microbubbles. These findings could lead to effective strategies for myocardial perfusion imaging with venous injections of microbubbles.
Albumins↗
Three-dimensional myocardial contrast echocardiography: validation of in vivo risk and infarct volumes.
OBJECTIVES: The aim of this study was to determine whether three-dimensional (3D) myocardial contrast echocardiography (MCE) could provide an accurate in vivo assessment of risk and infarct volumes. BACKGROUND: MCE has been shown to accurately define risk area and infarct size in single tomographic slices. The ability of this technique to measure risk and infarct volumes by using three-dimensional echocardiography (3DE) has not been determined. METHODS: Fifteen open chest dogs underwent variable durations of coronary artery occlusion followed by reperfusion. At each stage, MCE was performed by using left atrial injection of AIP201, a deposit microbubble with a mean diameter of 10 +/- 4 microm and a mean concentration of 1.5 x 10(7) x ml(-1). Images were obtained over a 180 degree arc with use of an automated rotational device and were stored in computer as a 3D data set. Postmortem risk area and infarct size were measured in six to eight left ventricular short-axis slices of equal thickness using technetium-99m autoradiography and tissue staining, respectively. MCE images corresponding to these planes were reconstructed off-line. RESULTS: A close linear relation was noted between the volume of myocardium not showing contrast enhancement on 3D MCE during coronary occlusion and postmortem risk volume (y = 1.2x - 3.0, r = 0.83, SEE = 5.1, n = 15). The volume of myocardium not showing contrast enhancement on 3D MCE after reperfusion also closely correlated with postmortem infarct volume (y = 1.1x - 3.9, r = 0.88, SEE = 4.8, n = 11). No changes in systemic hemodynamic variables were noted with injections of AIP201. CONCLUSIONS: When combined with AIP201, a deposit microbubble, 3D MCE can be used to accurately determine both risk and infarct volumes in vivo. This method could be used to assess the effects of interventions that attempt to alter the infarct/risk volume ratio.
Animals↗
Influence of retinol deficiency and curcumin/turmeric feeding on tissue microsomal membrane lipid peroxidation and fatty acids in rats.
The effect of retinol deficiency and curcumin/turmeric on lipid peroxidation and fatty acid profile was studied in liver, kidney, spleen and brain microsomes of rats. Results revealed an increase in lipid peroxidation in retinol deficient liver by 32%, kidney 30%, spleen 24% and brain 43% compared to the controls. Feeding 0.1% curcumin or turmeric for three weeks in diet to retinol deficient rats reduced the lipid peroxidation respectively to 12.5 or 22.6%, in liver, 23.7 or 24.1% in kidney, 14.4 or 18.0% in spleen and 16.0 or 31.4% in brain. Retinol deficiency lead to a reduction in the essential fatty acids. In liver C18:1 showed a reduction by 45.6%, C18:2 by 31.6% and C20:4 by 22.8%. In kidney C18:1 was reduced by 33.6%, 18:2 by 24.6% and 20:4 by 13.7%. In spleen and brain C18:1 showed a reduction by 10.2% and 33.9%, C18:2 by 37.9% and 12.1% and C20:4 by 15.7% and 35.3% respectively. Curcumin and turmeric fed group showed a significant increase in the abnormally reduced fatty acid levels.
Animals↗
Keratinolysis by poultry farm soil fungi.
Species of Chrysosporium, Malbranchea, Scopulariopsis, Microascus, and Gliocladium isolated from poultry farm soils were grown on two keratin media. All the test fungi could grow on keratin (human hair) and degrade it, releasing sulphydryl-containing compounds detected as extracellular keratinase, cysteine and total proteins. Glucose supplemented keratin medium supported maximum keratinolysis. Keratinase activity also changed the pH of the medium towards alkalinity and species with strong keratinolytic ability were noted to render the culture medium more alkaline than those that were less kiratinolytic.
Animal Husbandry↗