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Jonathan R Lindner

Publications and source records attributed to Jonathan R Lindner.

48 records · Page 3Linked to original sources
PubMed2002

Noninvasive imaging of myocardial reperfusion injury using leukocyte-targeted contrast echocardiography.

BACKGROUND: We hypothesized that myocardial contrast echocardiography (MCE) with leukocyte-targeted microbubbles could temporally and spatially characterize the severity of postischemic myocardial inflammation. METHODS AND RESULTS: In 9 open-chest dogs, either the left anterior descending or left circumflex coronary artery was occluded for 90 minutes (n=6), while the remaining dogs served as non-ischemic controls. During occlusion, MCE was performed to determine the risk area (RA) and regions supplied by collateral flow. Myocardial inflammation was assessed 5, 60, and 120 minutes after reflow by MCE imaging of leukocyte-targeted (phosphatidylserine-containing) lipid microbubbles. The spatial extent and severity of inflammation were also assessed by radionuclide imaging of the neutrophil-avid tracer 99mTcRP517 and tissue myeloperoxidase activity. Early after reflow, MCE detected inflammation throughout the entire risk area, the extent of which decreased over time due to reduced signal in collateral-supplied regions. The spatial extent of inflammation late after reflow was similar for MCE and radionuclide imaging. The severity of inflammation in the infarct zone, the noninfarcted risk area, and collateral-supplied territories determined by quantitative MCE correlated well with myeloperoxidase activity (r=0.81). CONCLUSIONS: MCE with leukocyte-targeted microbubbles can temporally assess the severity and extent of postischemic myocardial inflammation and could be used to evaluate new treatment strategies designed to limit inflammation in acute coronary syndromes.

Animals↗
PubMed2002

Myocardial and microcirculatory kinetics of BR14, a novel third-generation intravenous ultrasound contrast agent.

OBJECTIVES: This study sought to investigate the myocardial and microvascular kinetics of BR14, a novel third-generation ultrasound contrast agent. BACKGROUND: BR14 produces persistent myocardial opacification after the administration of a single intravenous bolus when the left ventricular cavity contrast has considerably diminished. The mechanism of this finding is unknown. METHODS: Nine open-chest dogs with non-critical stenosis of a single coronary artery were given intravenous bolus injections of BR14 during coronary hyperemia. Time versus acoustic intensity (AI) plots were generated from the normal and stenosed beds and myocardial blood flow (MBF) was measured with radiolabeled microspheres. Intravital microscopy was performed on an exteriorized cremaster muscle in 11 wild-type mice to study the microvascular kinetics of the agent. RESULTS: At peak contrast enhancement, the ratio between AI in the stenosed and normal bed was 0.44+/-0.23, which was similar to the radiolabeled microsphere-derived MBF ratio between the two beds (0.45 +/-0.20). At 400 s after injection, the AI ratio between the two beds approximated unity (0.99+/-0.07) despite no changes in MBF, indicating redistribution of the agent. The myocardial kinetics of BR14 was best characterized by a modified lagged normal density function. Only about 3% of administered microbubbles were estimated to be retained in the myocardium. Intravital microscopy showed that most of these bubbles were retained only transiently (2 to 3 s) within capillaries. CONCLUSIONS: BR14 demonstrates redistribution because of transient retention within capillaries. Therefore, similar to (201)Tl, it could potentially be used to detect both coronary stenosis and myocardial viability after a single injection during stress.

Animals↗
PubMed2002

Skin perfusion assessed by contrast ultrasound predicts tissue survival in a free flap model.

The purpose of this study was to assess perfusion in a free skin flap model using contrast-enhanced ultrasound (CEU), and to determine if the extent of perfusion early after venous occlusion predicted long-term flap survival. Perfusion was assessed in an autologous abdominal skin flap and adjacent healthy skin in rats using CEU imaging before venous occlusion and following reflow. Perfusion assessment was possible in all flaps and quantitative measurements of microvascular blood volume (BV) and blood velocity were expressed as a ratio to that in the healthy skin. Proximal flap BV 18 h after venous occlusion was significantly greater in those that survived (n = 4) vs. those that became necrotic (n = 6) (BV ratio 0.8 +/- 0.1 vs. 0.2 +/- 0.1, p = 0.0001). A BV ratio of 0.5 predicted graft viability with a sensitivity and specificity of 100%. Microvascular blood velocity at 18 h was similar in grafts that survived and those that became necrotic. Qualitative assessment of perfusion by a "blinded" observer correlated well with quantitative data and predicted flap outcome in all cases. We conclude that skin perfusion can be assessed with CEU. Perfusion 18 h following a secondary ischemic insult in a free flap accurately predicts subsequent tissue survival in this model.

Abdomen↗
PubMed2002

Assessment of myocardial viability with myocardial contrast echocardiography.

The application of noninvasive imaging techniques to assess myocardial viability has become an important part of routine management of patients with acute myocardial infarction and chronic coronary artery disease. Information regarding the presence and extent of viability may help identify patients likely to benefit from revascularization or therapy directed at attenuating left ventricular remodeling. Myocardial contrast echocardiography (MCE) is capable of defining the presence and extent of viability by providing an accurate assessment of microvascular integrity needed to maintain myocellular viability. It is especially suited for the spatial assessment of perfusion, even when myocardial blood flow is reduced substantially in the presence of severe epicardial stenoses or in a bed dependent on collateral perfusion. The routine use of MCE to evaluate viability in patients with acute and chronic coronary artery disease is now feasible with the advent of new imaging technologies and microbubble agents capable of myocardial opacification from venous injections. The utility of this technique for determining treatment strategies has not been established but is forthcoming.

Acute Disease↗
PubMed2002

Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration.

The microvascular rheology and extent of pulmonary retention of second-generation microbubble ultrasound contrast agents has not previously been well characterized. We assessed the microvascular behavior of Definity, a lipid-shelled microbubble agent containing perfluoropropane gas, using intravital microscopy of either rat spinotrapezius muscle or mouse cremaster muscle. Immediately after intra-arterial injection, which was performed to model pulmonary retention, larger microbubbles (> 5 microm) were entrapped within small arterioles and capillaries. The retention fraction of microbubbles was low (1.2% +/- 0.1%) and entrapment was transient (85% dislodged by 10 minutes), resulting in no adverse hemodynamic effects. Leukocyte or platelet adhesion at the site of entrapment was not seen. After intravenous injection, no microbubble entrapment was observed and the velocities of microbubbles in arterioles, venules, and capillaries correlated well with those of red blood cells. We conclude that after intravenous injection and pulmonary passage, the microvascular rheology of Definity microbubbles is similar to that of red blood cells. Microbubble entrapment within the pulmonary microcirculation after venous injection should be negligible and transient. These findings are important for establishing the safety of this agent.

Animals↗
PubMed2002

Relation between myocardial oxygen consumption and myocardial blood volume: a study using myocardial contrast echocardiography.

Myocardial blood volume (MBV) is the volume of blood residing in myocardial vessels, 90% of which is in capillaries. MBV can be measured in vivo using myocardial contrast echocardiography (MCE). It has been shown that when increases in coronary blood flow (CBF) are not associated with increase in myocardial oxygen consumption (MVO(2)), MBV does not increase. We hypothesized that MBV would increase when increases in CBF are associated with an increase in MVO(2). The atrioventricular node was ablated in 18 dogs and dual-chamber pacing was instituted. In group 1 dogs (n = 9), heart rate was altered from 50 to 150 bpm(-1) in increments of 20 bpm(-1) in random order. In group 2 dogs (n = 9), heart rate was kept constant, and dobutamine was infused at doses of 5, 10, 20, 30, and 40 microg/kg(-1)/min(-1). During each intervention, hemodynamic parameters and MVO(2) were measured, and MCE was performed. MVO(2) increased more (P <.01) with inotropic compared with chronotropic stimulation, resulting in a parallel increase in CBF. MBV fraction and MCE-derived myocardial blood flow increased significantly with increases in MVO(2) (P <.05 and P <.001, respectively) when dobutamine was infused, but remained unchanged when heart rate alone was increased. We conclude that when MVO(2) is increased substantially, the resulting increase in CBF and MCE-derived myocardial blood flow is mediated, in part, by an increase in MBV. Thus, capillary recruitment plays an important role in the physiologic regulation of CBF. Lack of increase in MBV during dobutamine stress may indicate the presence of coronary stenosis or microvascular disease.

Animals↗
PubMed2002

Influence of microbubble shell properties on ultrasound signal: Implications for low-power perfusion imaging.

Low mechanical index perfusion imaging relies on the detection of signals produced by microbubble oscillation at low acoustic powers that results in minimal microbubble destruction. We hypothesized that the optimal acoustic power for real-time imaging would differ for microbubbles with different shell characteristics. Three microbubble agents with varying shell elastic properties according to their polymer composition were studied. Differences in the elastic properties of these microbubbles was demonstrated by: (1) measurement of their bulk modulus and (2) evaluation of their acoustic lability by microscopic visualization of microbubble destruction during insonification at incremental acoustic powers. The ultrasound signal generated by these microbubbles at various mechanical indexes and the degree of microbubble destruction during continuous imaging was determined both in an in vitro flow system and during in vivo imaging in an open-chest canine model. Both studies indicated that optimal power for achieving maximal signal intensity with minimal microbubble destruction was influenced by the shell elastic properties. We conclude that the acoustic power for maximizing acoustic signal without destroying microbubbles during low mechanical index imaging varies according to shell characteristics.

Acoustics↗
PubMed2002

Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi.

RATIONALE AND OBJECTIVES: New targeted microbubbles directed to the GPIIb IIIa receptor have been developed. The objective was to determine whether targeting microbubbles to clots would enhance ultrasound imaging. Systematic studies were designed to determine whether in vitro methodology is an acceptable predictor of in vivo efficacy. MATERIALS AND METHODS: Bioconjugate ligands were inserted into lipid-coated membranes of perfluorocarbon gas microbubbles and binding studies performed on activated platelets immobilized on cell culture plates. Targeted microbubble binding to clots in a flow through chamber was also assessed. Finally, microbubble binding studies on arteriolar and venular clots in a mouse cremasteric muscle model were conducted. RESULTS: Binding studies on platelet-immobilized plates demonstrated an affinity for targeted microbubbles versus untargeted microbubbles. Semiquantitative light obscuration techniques helped to measure extent of targeted microbubble binding. Targeted microbubbles similarly bound to platelet clots in the flow model. Finally, studies in the mouse model confirmed binding of targeted microbubbles in both venules and arterioles. CONCLUSION: The use of receptor selective targeted microbubbles improved binding to vascular thrombi in both in vitro and in vivo settings.

Animals↗
PubMed2002

Vascular recruitment in skeletal muscle during exercise and hyperinsulinemia assessed by contrast ultrasound.

The purpose of this study was to noninvasively quantify the effects of insulin on capillary blood volume (capBV) and RBC velocity (V(RBC)) in skeletal muscle in vivo with the use of contrast-enhanced ultrasound. We performed contrast ultrasound of the rat hindlimb adductor muscles at baseline and after 2-h infusions of either insulin (3 or 40 mU x kg(-1) x min(-1)) or saline. Saline-treated animals were also studied during contractile exercise. V(RBC) and capBV were calculated from the relation between pulsing interval and video intensity. Femoral artery blood flow, measured by a flow probe, increased with both contractile exercise and insulin. Contractile exercise increased capBV more than twofold and V(RBC) fivefold. Insulin also increased capBV more than twofold in a dose-dependent fashion but did not significantly alter V(RBC). Saline infusion did not significantly alter capBV, V(RBC), or femoral artery blood flow. We conclude that physiological changes in skeletal muscle capillary perfusion can be assessed in vivo with the use of contrast-enhanced ultrasound. Exercise increases both V(RBC) and capBV, whereas hyperinsulinemia selectively increases only capBV, which may enhance skeletal muscle glucose uptake.

Animals↗
PubMedDate not supplied

The vasodilatory actions of insulin on resistance and terminal arterioles and their impact on muscle glucose uptake.

Whether a discrete vascular action of insulin in skeletal muscle integrally participates in insulin-mediated glucose disposal has been extensively examined but remains a contentious issue. Here, we review some of the data both supporting and questioning the role of insulin-mediated increases in limb blood flow in glucose metabolism. We advance the hypothesis that controversy has arisen, at least in part, from a failure to recognize that insulin exerts at least three separate actions on the peripheral vasculature, each with its own characteristic dose and time responsiveness. We summarize how, viewed in this manner, certain points of contention can be resolved. We also advance the hypothesis that an action on the precapillary arteriole may play the dominant role in mediating perfusion-dependent effects of insulin on glucose metabolism in muscle.

Animals↗
PubMedDate not supplied

Molecular imaging with contrast ultrasound and targeted microbubbles.

There is growing interest in the development of methods for imaging cellular and molecular mediators of cardiovascular diseases. Techniques for imaging molecular and cellular alterations have been explored for essentially all noninvasive cardiac imaging modalities. Molecular imaging with contrast-enhanced ultrasound relies on the detection of novel site-targeted microbubble contrast agents. These microbubbles are retained within regions of a specific disease process, thereby allowing phenotypic characterization of tissue. As microbubbles are pure intravascular tracers, the disease processes assessed must be characterized by antigens that are expressed within the vascular compartment. Accordingly, the pathologic states that have been targeted include inflammation, neoplasms, angiogenesis, and thrombus formation, all of which are mediated in part by molecular events within the vascular space. This review describes (1) different strategies that have been used to target microbubbles to regions of disease, (2) the unique challenges for imaging targeted ultrasound contrast agents, and (3) some of the early experience imaging molecular events in animal models of disease.

Animals↗