Biomedical subjects

J R Lindner

Publications and source records attributed to J R Lindner.

30 records · Page 2Linked to original sources

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

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↗

PubMed1997

Changes in myocardial blood volume with graded coronary stenosis.

Vasodilation of microvessels distal to a stenosis results in an increase in myocardial blood volume (MBV). The purpose of this study was to examine the changes in MBV induced by graded coronary artery stenoses by using myocardial contrast echocardiography (MCE). Accordingly, 21 dogs underwent progressive stenosis of a coronary artery in a random order, the severity of which was judged by the pressure distal to it. Total myocardial blood flow (MBF) to the bed distal to the artery (both anterograde and collateral) was measured by injection of radiolabeled microspheres into the left atrium. In seven dogs, anterograde and total MBF were measured at each stenosis stage by injection of different microspheres into the left atrium and directly into the coronary artery, respectively. MBV was calculated by dividing MBF by the mean transit rate of microbubbles injected directly into the coronary artery during MCE. The perfusion bed size of the artery was also measured by MCE. Our major findings are as follows: 1) there is a nonlinear increase in MBV with increasing degrees of coronary stenosis until the coronary stenosis becomes critical; 2) at moderate levels of coronary stenosis, MBV remains constant despite ongoing autoregulation because of reduction in the size of the perfusion bed supplied by the stenotic vessel; and 3) after exhaustion of autoregulation, a decrease in MBV is noted with increasing levels of stenosis. We conclude that assessment of MBV provides insights into myocardial perfusion distal to a coronary stenosis above and beyond that provided by the measurement of MBF alone.

Animals↗

PubMed1997

Modeling the myocardial dilution curve of a pure intravascular indicator.

The dispersion and dilution of contrast medium through the myocardial vasculature is examined first with a serial model comprised of arterial, capillary, and venous components in series to determine their time-concentration curves (TCC) and the myocardial dilution curve (MDC). Analysis of general characteristics shows that the first moment of the MDC, adjusted for that of the aortic TCC and mean transit time (MTT) from the aorta to the first intramyocardial artery, is one-half the MTT of the myocardial vasculature and that the ratio of the area of the MDC and aortic TCC is the fractional myocardial blood volume (MBV). The use of known coronary vascular morphometry and a set of transport functions indicates that the temporal change in MDC is primarily controlled by the MTT. An analysis of several models with heterogeneous flow distributions justifies the procedures to calculate MTT and MBV from the measured MDC. Compared with previously described models, the present model is more general and provides a physical basis for the effects of flow dispersion and heterogeneity on the characteristics of the MDC.

Animals↗

PubMed1996

Diagnostic value of echocardiography in suspected endocarditis. An evaluation based on the pretest probability of disease.

BACKGROUND: We hypothesized that for the diagnosis of endocarditis, (1) transthoracic echocardiography (TTE) would be most valuable in patients with an intermediate clinical probability of the disease and (2) transesophageal echocardiography (TEE) would be most useful in patients with an intermediate probability when TTE either does not yield an adequate study or indicates an intermediate probability of endocarditis. We also sought to investigate the influence of echocardiographic results on antibiotic usage and its duration. METHODS AND RESULTS: TTE and TEE were performed in 105 consecutive patients with suspected endocarditis. Patients were classified as having either low, intermediate, or high probability of endocarditis on the basis of clinical criteria and separately on the basis of both TTE and TEE findings. TTE and TEE classified the majority (82% and 85%, respectively) of the 67 patients with a low clinical probability of endocarditis as having a low likelihood of the disease. Of the 14 patients with intermediate clinical probability, 12 had technically adequate TTE studies; 10 of these (83%) were classified as either high or low probability. All patients with intermediate clinical probability were classified as high or low probability by TEE. The majority of the 24 patients with high clinical probability were placed in the low-likelihood category by echocardiography (15 by TTE and 12 by TEE). There was concordance between TTE and TEE in 83% of all cases. TEE was useful for the diagnosis of endocarditis in patients with prosthetic valves and in those in whom TTE indicated an intermediate probability; these constituted < 20% of patients in our study. The course of antibiotic therapy was influenced only by the clinical profile and not by the echocardiographic results. CONCLUSIONS: Echocardiography should not be used to make a diagnosis of endocarditis in those with a low clinical probability of the disease. In those with an intermediate or high clinical probability, TTE should be the diagnostic procedure of choice. TEE for the diagnosis of endocarditis should be reserved only for patients who have prosthetic valves and in whom TTE is either technically inadequate or indicates an intermediate probability of endocarditis.

Adolescent↗

PubMedDate not supplied

Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow.

Targeted ultrasound contrast materials (gas-filled microbubbles carrying ligands to endothelial selectins or integrins) have been investigated as potential molecular imaging agents. Such microbubbles normally exhibit good targeting capability at the slower flow conditions. However, in the conditions of vigorous flow, binding may be limited. Here, we describe a microbubble capable of efficient binding to targets both in slow and fast flow (exceeding 4 dyne/cm(2) wall shear stress) using a clustered polymeric form of the fast-binding selectin ligand sialyl Lewis(X). Microbubbles were prepared from decafluorobutane gas and stabilized with a monolayer of phosphatidylcholine, PEG stearate and biotin-PEG-lipid. Biotinylated PSLe(x) (sialyl Lewis(X) polyacrylamide) or biotinylated anti-P-selectin antibody (RB40.34) was attached to microbubbles via a streptavidin bridge. In a parallel plate flow chamber targeted adhesion model, PSLe(x) bubbles demonstrated specific adhesion, retention and slow rolling on P-selectin-coated plates. Efficiency of firm targeted adhesion to a P-selectin surface (140 molecules/microm(2)) was comparable for antibody-carrying bubbles and PSLe(x)-targeted bubbles at 0.68 dyne/cm(2) shear stress. At fast flow (4.45 dyne/cm(2)), PSLe(x)-targeted bubbles maintained their ability to bind, while antibody-mediated targeting dropped more than 20-fold. At lower surface density of P-selectin (7 molecules/microm(2)), targeting via PSLe(x) was more efficient than via antibody under all the flow conditions tested. Negative control casein-coated plates did not retain bubbles in the range of flow conditions studied. To confirm echogenicity, targeted PSLe(x)-bubbles were visualized on P-selectin-coated polystyrene plates by ultrasound imaging with a clinical scanner operated in pulse inversion mode; control plates lacking targeted bubbles did not show significant acoustic backscatter. In vivo, in a murine model of inflammation in the femoral vein setting, targeting efficacy of intravenously administered PSLe(x)-microbubbles was comparable with targeting mediated by anti-P-selectin antibody, and significantly exceeded the accumulation of non-targeted control bubbles. In the inflamed femoral artery setting, PSLe(x)-mediated microbubble targeting was superior to antibody-mediated targeting.

Acrylic Resins↗

PubMedDate not supplied

Insights into the assessment of myocardial perfusion offered by different cardiac imaging modalities.

Myocardial perfusion may be very broadly defined as the tightly regulated nutrient delivery to cardiac tissue. The different components of perfusion are myocardial blood flow, oxygen delivery, myocardial oxygen consumption, and myocardial blood volume. Historically, focus has been placed mostly on the assessment of blood flow. In many instances, knowledge of flow without information about these other aspects is inadequate. This review discusses the various cardiac imaging techniques used for the assessment of myocardial perfusion that represent diverse physiologic measures of "perfusion." Their strengths and limitations are discussed as is their relevance to specific clinicopathologic conditions. Significant work still needs to be performed before all the aspects of myocardial perfusion can be precisely measured in human beings.

Blood Volume↗

PubMedDate not supplied

Assessment of myocardial viability with two-dimensional echocardiography and magnetic resonance imaging.

In a patient with coronary artery disease, clinical, electrocardiographic, and angiographic information is often inadequate for determining the presence of viable tissue. The presence of wall thickening, even if reduced, indicates that the myocardium is viable. When wall thickening is absent, the myocardium may or may not be viable. The basis for the underlying myocardial dysfunction may be multifactorial in a single patient or even in a single myocardial segment. Cardiac imaging techniques are most useful in defining the mechanisms of underlying myocardial dysfunction and assist in selecting the optimal management strategy for patients. This review discusses the role of two-dimensional echocardiography and magnetic resonance imaging for the assessment of myocardial viability.

Coronary Disease↗

PubMedDate not supplied

Assessment of inflammation with contrast ultrasound.

Future clinical applications of contrast-enhanced ultrasound will likely expand beyond the assessment of microvascular perfusion. One promising direction is the development of site-targeted microbubbles that are retained within regions of a specific disease process and thereby allow phenotypic characterization of tissue. Inflammation is an ideal disease state for targeting with microbubbles because the pathophysiologic processes that initiate and support the inflammatory response occur within the microcirculation, where microbubbles reside. This review describes methods that have been used to direct microbubbles to regions of inflammation. These methods rely on either (1) intrinsic properties of albumin or lipid microbubbles that promote their attachment to leukocyte adhesion molecules, or (2) conjugation of monoclonal antibodies or other ligands to the microbubble surface that recognize specific endothelial cell adhesion molecules. This review also considers ultrasound imaging methods that may be used to detect microbubbles retained within inflamed tissue.

Cell Adhesion Molecules↗