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Biomedical subjects

J R Lindner

Publications and source records attributed to J R Lindner.

At least 19 recordsLinked to original sources
PubMed2003

Inhibiting NOS blocks microvascular recruitment and blunts muscle glucose uptake in response to insulin.

We examined the effects of inhibiting nitric oxide synthase with Nomega-nitro-l-arginine-methyl ester (l-NAME) on total hindlimb blood flow, muscle microvascular recruitment, and hindlimb glucose uptake during euglycemic hyperinsulinemia in vivo in the rat. We used two independent methods to measure microvascular perfusion. In one group of animals, microvascular recruitment was measured using the metabolism of exogenously infused 1-methylxanthine (1-MX), and in a second group contrast-enhanced ultrasound (CEU) was used. Limb glucose uptake was measured by arterial-venous concentration differences after 2 h of insulin infusion. Saline alone did not alter femoral artery flow, glucose uptake, or 1-MX metabolism. Insulin (10 mU.min-1.kg-1) significantly increased hindlimb total blood flow (0.69 +/- 0.02 to 1.22 +/- 0.11 ml/min, P < 0.05), glucose uptake (0.27 +/- 0.05 to 0.95 +/- 0.08 micromol/min, P < 0.05), 1-MX uptake (5.0 +/- 0.5 to 8.5 +/- 1.0 nmol/min, P < 0.05), and skeletal muscle microvascular volume measured by CEU (10.0 +/- 1.6 to 15.0 +/- 1.2 video intensity units, P < 0.05). Addition of l-NAME to insulin completely blocked the effect of insulin on both total limb flow and microvascular recruitment (measured using either 1-MX or CEU) and blunted glucose uptake by 40% (P < 0.05). We conclude that insulin specifically recruits flow to the microvasculture in skeletal muscle via a nitric oxide-dependent pathway and that this may be important to insulin's overall action to regulate glucose disposal.

Animals↗
PubMed2002

Skeletal muscle microvascular recruitment by physiological hyperinsulinemia precedes increases in total blood flow.

Supraphysiological doses of insulin enhance total limb blood flow and recruit capillaries in skeletal muscle. Whether these processes change in response to physiological hyperinsulinemia is uncertain. To examine this, we infused either saline (n = 6) or insulin (euglycemic clamp, 3.0 mU x min(-1) x kg(-1), n = 9) into anesthetized rats for 120 min. Femoral artery flow was monitored continuously using a Doppler flow probe, and muscle microvascular recruitment was assessed by metabolism of infused 1-methylxanthine (1-MX) and by contrast-enhanced ultrasound (CEU). Insulin infusion raised plasma insulin concentrations by approximately 10-fold. Compared with saline, physiological hyperinsulinemia increased femoral artery flow (1.02 +/- 0.10 vs. 0.68 +/- 0.09 ml/min; P < 0.05), microvascular recruitment (measured by 1-MX metabolism [6.6 +/- 0.5 vs. 4.5 +/- 0.48 nmol/min; P < 0.05] as well as by CEU [167.0 +/- 39.8 vs. 28.2 +/- 13.8%; P < 0.01]), and microvascular flow velocity (beta, 0.14 +/- 0.02 vs. 0.09 +/- 0.02 s(-1)). Subsequently, we studied the time dependency of insulin's vascular action in a second group (n = 5) of animals. Using CEU, microvascular volume was measured at 0, 30, and 90 min of insulin infusion. Insulin augmented microvascular perfusion within 30 min (52.8 +/- 14.8%), and this persisted at 90 min (64.6 +/- 9.9%). Microvascular recruitment occurred without changes to femoral artery flow or beta. We conclude that insulin increases tissue perfusion by recruiting microvascular beds, and at physiological concentrations this precedes increases in total muscle blood flow by 60-90 min.

Animals↗
PubMed2001

Decrease in coronary blood flow reserve during hyperlipidemia is secondary to an increase in blood viscosity.

BACKGROUND: During maximal hyperemia, capillaries provide the greatest resistance to flow. A major determinant of capillary resistance is viscosity. We, therefore, hypothesized that abnormal coronary blood flow (CBF) reserve observed during hyperlipidemia is secondary to increased blood viscosity and not abnormal coronary vasomotion. METHODS AND RESULTS: Maximal hyperemia was induced in 9 dogs using adenosine. Serum triglyceride levels were increased by incremental doses of Intralipid. A good correlation was noted between serum triglyceride levels and blood viscosity (r=0.82). Neither total coronary blood volume nor myocardial blood volume changed with increasing serum triglyceride levels, indicating lack of vasomotion. Myocardial vascular resistance (MVR) increased with increasing triglyceride levels (r=0.84), while hyperemic myocardial blood flow (MBF) decreased (r=-0.64). The decrease in hyperemic MBF was associated with a decrease in blood velocity (r=-0.56). These findings were confirmed with direct intravital microscopic observations in the mice cremaster muscle. CONCLUSIONS: Increasing lipid levels in a fully dilated normal coronary bed causes no change in large or small vessel dimensions. Instead, the increase in blood viscosity causes capillary resistance to rise, which attenuates hyperemic CBF. Therefore, the abnormal CBF reserve associated with hyperlipidemia is due to increase blood viscosity and not abnormal vascular function.

Adenosine↗
PubMed2001

Quantification of cerebral perfusion with "Real-Time" contrast-enhanced ultrasound.

BACKGROUND: No noninvasive technique is currently capable of "real-time" assessment and monitoring of cerebral blood flow (CBF). We hypothesized that cerebral perfusion could be accurately measured and monitored in "real time" with contrast-enhanced ultrasound (CEU). METHODS AND RESULTS: Cerebral perfusion was assessed in 9 dogs through a craniotomy with CEU at baseline and during hypercapnia and hypocapnia while normoxia was maintained. Cerebral microvascular blood volume (A), microbubble velocity (beta), and blood flow (Axbeta) were calculated from time-versus-acoustic intensity relations. Compared with baseline, hypercapnia and hypocapnia significantly increased and decreased CBF, respectively, as measured by CEU. These changes in blood flow were mediated by changes in both A and beta. A good correlation was found between Axbeta derived from CEU and CBF measured by radiolabeled microspheres (y=0.67x-0.04, r=0.91, P<0.001). CONCLUSIONS: Changes in both cerebral microvascular blood volume and red blood cell velocity can be accurately assessed with CEU. Thus, CEU has the potential for bedside measurement and monitoring of cerebral perfusion in real time in patients with craniotomies or burr holes.

Animals↗
PubMed2001

Noninvasive prediction of ultimate infarct size at the time of acute coronary occlusion based on the extent and magnitude of collateral-derived myocardial blood flow.

BACKGROUND: We hypothesized that by detecting regions with adequate collateral-derived myocardial blood flow (MBF) within the risk area (RA), we could predict ultimate infarct size (IS) at the time of coronary occlusion. METHODS AND RESULTS: Group 1 dogs (n=15) underwent coronary occlusion without reperfusion, whereas group 2 dogs (n=6) underwent both occlusion and reperfusion. RA was measured with aortic root injections of microbubbles. Myocardial contrast echocardiography (MCE) was performed with high mechanical index intermittent harmonic imaging at pulsing intervals (PIs) of <1 to 30 cardiac cycles during an intravenous infusion of microbubbles (Sonozoid). MBF was measured with radiolabeled microspheres, and postmortem tissue staining was used to determine IS. Perfusion defect size (PDS) on MCE varied with the PI and was largest at a PI of 2.6+/-0.4 seconds, where it correlated well with RA (r=0.82). PDS was smallest at a PI of >/=10.6+/-1.5 seconds, where it correlated closely with IS (r>/=0.92). Areas that underwent necrosis could be identified early after coronary occlusion as having the lowest microvascular flow velocity (beta) and MCE-derived MBF (Axbeta). The results were similar with or without reperfusion. Because of variability in collateral-derived MBF, there was no correlation between RA and ultimate IS (P=0.37). The extent of regional dysfunction also correlated poorly with IS (r=0.31). CONCLUSIONS: MCE can be used immediately after coronary occlusion to define ultimate IS by measuring the magnitude and spatial extent of collateral-derived residual MBF within the RA. Thus, it could help individualize risk and management in acute myocardial infarction.

Animals↗
PubMed2001

Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin.

BACKGROUND: Routine methods capable of assessing tissue inflammation noninvasively are currently not available. We hypothesized that tissue retention of microbubbles targeted to the endothelial cell adhesion molecule P-selectin would provide a means to assess inflammation with ultrasound imaging. METHODS AND RESULTS: Phospholipid microbubbles targeted to P-selectin (MB(p)) were created by conjugating monoclonal antibodies against murine P-selectin to the lipid shell. The microvascular behaviors of MB(p) and control microbubbles without antibody (MB) or with isotype control antibody (MB(iso)) were assessed by intravital microscopy of cremasteric venules of control and tumor necrosis factor (TNF)-alpha-stimulated wild-type mice. Retention of all microbubbles increased (P<0.05) with TNF-alpha treatment because of increased attachment to activated leukocytes. Extensive attachment of MB(p) directly to the venular endothelium or to adherent platelet-leukocyte aggregates was observed in TNF-alpha-stimulated mice, resulting in 4-fold greater (P<0.01) retention of MB(p) than either MB(iso) or MB. Enhanced retention of MB(p) was completely abolished in TNF-alpha-stimulated P-selectin-deficient mice. The ultrasound signal from microbubbles retained in inflamed tissue was assessed by contrast-enhanced renal ultrasound imaging of the kidneys of mice undergoing ischemia-reperfusion injury. In wild-type mice, this signal was significantly higher (P<0.05) for MB(p) (12+/-2 U) than either MB(iso) (6+/-3 U) or MB (5+/-3 U). In P-selectin-deficient mice, the signal for MB(p) was equivalent to that from control microbubbles. CONCLUSIONS: Microvascular retention of microbubbles targeted to P-selectin produces strong signal enhancement on ultrasound imaging of inflamed tissue. These results suggest that site-targeted microbubbles may be used to assess inflammation, tissue injury, and other endothelial responses noninvasively with ultrasound.

Animals↗
PubMed2001

Optical and acoustical dynamics of microbubble contrast agents inside neutrophils.

Acoustically active microbubbles are used for contrast-enhanced ultrasound assessment of organ perfusion. In regions of inflammation, contrast agents are captured and phagocytosed by activated neutrophils adherent to the venular wall. Using direct optical observation with a high-speed camera and acoustical interrogation of individual bubbles and cells, we assessed the physical and acoustical responses of both phagocytosed and free microbubbles. Optical analysis of bubble radial oscillations during insonation demonstrated that phagocytosed microbubbles experience viscous damping within the cytoplasm and yet remain acoustically active and capable of large volumetric oscillations during an acoustic pulse. Fitting a modified version of the Rayleigh-Plesset equation that describes mechanical properties of thin shells to optical radius-time data of oscillating bubbles provided estimates of the apparent viscosity of the intracellular medium. Phagocytosed microbubbles experienced a viscous damping approximately sevenfold greater than free microbubbles. Acoustical comparison between free and phagocytosed microbubbles indicated that phagocytosed microbubbles produce an echo with a higher mean frequency than free microbubbles in response to a rarefaction-first single-cycle pulse. Moreover, this frequency increase is predicted using the modified Rayleigh-Plesset equation. We conclude that contrast-enhanced ultrasound can detect distinct acoustic signals from microbubbles inside of neutrophils and may provide a unique tool to identify activated neutrophils at sites of inflammation.

Contrast Media↗
PubMed2001

Delivery of drugs with ultrasound.

In this article we discuss the potential role of microbubbles, traditionally used as ultrasound contrast agents, for site-specific drug delivery. To reach this goal, microbubbles capable of carrying a drug payload are being developed. To ensure that these microbubbles reach sufficient local concentration at disease sites, specific targeting for diseased tissues can be accomplished using several strategies. These strategies rely on either the intrinsic properties of microbubble shells or conjugation of monoclonal antibodies or other ligands to these shells that recognize antigens expressed in regions of disease. Site-specific delivery of antiinflammatory, antineoplastic, and thrombolytic drugs with microbubbles can be further enhanced by the ability to locally destroy microbubbles within an acoustic field, thereby releasing drugs and improving drug efficacy without systemic adverse effects. In the case of thrombi, ultrasound-mediated microbubble destruction also may facilitate the process of clot lysis. This review also will consider current limitations and technological advances required for the development of this field.

Contrast Media↗
PubMed2001

Texas entry-year agriculture teachers' perceptions, practices, and preparation regarding safety and health in agricultural education.

The purpose of this study was to gather benchmark data for the assessment of the knowledge, attitudes, and perceptions regarding agricultural safety issues and curricula held by Texas agricultural teachers with less than two full years of teaching experience (entry-year teachers). Seventy-four of 118 well-distributed teachers responded to this survey. Researchers concluded that more females were entering a traditionally male-dominated field. Overall, teachers addressed safety within units of instruction rather than as separate units. The most useful forms of new teaching resources that this group of teachers would like to see produced were safety videos and study guides, and class demonstration/simulation activities. There was a significant difference in rankings between teachers less than 26 years old and teachers more than 26 years old regarding the usefulness of transparencies as a new teaching resource (F = 5.00, p = 0.0268). Few teachers were currently CPR and first aid certified, even though most had received training and completed a general safety and/or health related course while in college. Teachers generally agreed philosophically with most practices and exhibited personal beliefs consistent with proper safety preparedness and practice in agricultural settings. However, many of these teachers failed to practice what was expected of safe tractor operators, such as wearing safety belts and allowing younger drivers to operate the equipment.

Adult↗
PubMed2000

Delayed onset of inflammation in protease-activated receptor-2-deficient mice.

Endothelial surface expression of P-selectin and subsequent leukocyte rolling in venules can be induced by mast cell-derived histamine and binding of thrombin to protease-activated receptor-1 (PAR1). We hypothesized that activation of endothelial PAR2 by mast cell tryptase or other proteases also contributes to inflammatory responses. Leukocyte rolling flux and rolling velocity were assessed by intravital microscopy of the cremaster muscles of wild-type mice following perivenular micropipette injections of a control (LSIGRL) or PAR2-activating (SLIGRL) oligopeptide. Injection of SLIGRL increased mean rolling leukocyte flux fraction from 34 +/- 11 to 71 +/- 24% (p < 0.05) and decreased mean rolling velocity from 63 +/- 29 to 32 +/- 2 micrometer/s (p < 0.05). No significant changes occurred with control peptide injection. To further evaluate the role of PAR2 in inflammatory responses, PAR2-deficient mice were generated by gene targeting and homologous recombination. Perivenular injections of SLIGRL resulted in only a small increase in rolling leukocyte flux fraction (from 21 +/- 8 to 30 +/- 2%) and no change in rolling velocity. Leukocyte rolling after surgical trauma was assessed in 9 PAR2-deficient and 12 wild-type mice. Early (0-15 min) after surgical trauma, the mean leukocyte rolling flux fraction was lower (10 +/- 3 vs 30 +/- 6%, p < 0.05) and mean rolling velocity was higher (67 +/- 46 vs 52 +/- 36 micrometer/s, p < 0.01) in PAR2-deficient compared with control mice. The defect in leukocyte rolling in PAR2-deficient mice did not persist past 30 min following surgical trauma. These results indicate that activation of PAR2 produces microvascular inflammation by rapid induction of P-selectin-mediated leukocyte rolling. In the absence of PAR2, the onset of inflammation is delayed.

Animals↗
PubMed2000

Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes.

BACKGROUND: Lipid microbubbles used for perfusion imaging with ultrasound are retained within inflamed tissue because of complement-mediated attachment to leukocytes within venules. We hypothesized that incorporation of phosphatidylserine (PS) into the microbubble shell may enhance these interactions by amplifying complement activation and thereby allow ultrasound imaging of inflammation. METHODS AND RESULTS: In 6 mice, intravital microscopy of tissue necrosis factor-alpha-treated cremaster muscle was performed to assess the microvascular behavior of fluorescein-labeled lipid microbubbles with and without PS in the shell. Ten minutes after intravenous injection, microbubble attachment to leukocytes within inflamed venules was greater for PS-containing than for standard lipid microbubbles (20+/-4 versus 10+/-3 per 20 optical fields, P<0.05). The ultrasound signal from retained microbubbles was assessed in the kidneys of 6 mice undergoing renal ischemia-reperfusion injury and in 6 control kidneys. The signal from retained microbubbles in control kidneys was low (<2.5 video intensity units) for both agents. After ischemia-reperfusion, the signal from retained microbubbles was 2-fold higher for PS-containing than for standard lipid microbubbles (18+/-6 versus 8+/-2 video intensity units, P<0.05). An excellent relation was found between the ultrasound signal from retained microbubbles and the degree of renal inflammation, assessed by tissue myeloperoxidase activity. CONCLUSIONS: -We conclude that noninvasive assessment of inflammation is possible by ultrasound imaging of microbubbles targeted to activated leukocytes by the presence of PS in the lipid shell.

Animals↗
PubMed2000

Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles.

BACKGROUND: We have previously shown that microbubbles adhere to leukocytes in regions of inflammation. We hypothesized that these microbubbles are phagocytosed by neutrophils and monocytes and remain acoustically active, permitting their detection in inflamed tissue. METHODS AND RESULTS: In vitro studies were performed in which activated leukocytes were incubated with albumin or lipid microbubbles and observed under microscopy. Microbubbles attached to the surface of activated neutrophils and monocytes, were phagocytosed, and remained intact for up to 30 minutes. The rate of destruction of the phagocytosed microbubbles on exposure to ultrasound was less (P</=0.05) than that of free microbubbles at all acoustic pressures applied. Intravital microscopy and simultaneous ultrasound imaging of the cremaster muscle was performed in 6 mice to determine whether phagocytosed microbubbles could be detected in vivo. Fifteen minutes after intravenous injection of fluorescein-labeled microbubbles, when the blood-pool concentration was negligible, the number of phagocytosed/attached microbubbles within venules was 7-fold greater in tumor necrosis factor-alpha (TNF-alpha)-treated animals than in control animals (P<0.01). This increase in retained microbubbles resulted in a 5- to 6-fold-greater (P<0.01) degree of ultrasound contrast enhancement than in controls. CONCLUSIONS: After attaching to activated neutrophils and monocytes, microbubbles are phagocytosed intact. Despite viscoelastic damping, phagocytosed microbubbles remain responsive to ultrasound and can be detected by ultrasound in vivo after clearance of freely circulating microbubbles from the blood pool. Thus, contrast ultrasound has potential for imaging sites of inflammation.

Animals↗
PubMed2000

Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes.

BACKGROUND: Albumin microbubbles that are used for contrast echocardiography persist within the myocardial microcirculation after ischemia/reperfusion (I-R). The mechanism responsible for this phenomenon is unknown. METHODS AND RESULTS: Intravital microscopy of the microcirculation of exteriorized cremaster muscle was performed in 12 wild-type mice during intravenous injections of fluorescein-labeled microbubbles composed of albumin, anionic lipids, or cationic lipids. Injections were performed at baseline and after 30 to 90 minutes of I-R in 8 mice and 2 hours after intrascrotal tumor necrosis factor-alpha (TNF-alpha) in 4 mice. Microbubble adherence at baseline was uncommon (<2/50 high-power fields). After I-R, adherence increased (P<0.05) to 9+/-5 and 5+/-4 per 50 high-power fields for albumin and anionic lipid microbubbles, respectively, due to their attachment to leukocytes adherent to the venular endothelium. TNF-alpha produced even greater microbubble binding, regardless of the microbubble shell composition. The degree of microbubble attachment correlated (r=0.84 to 0.91) with the number of adhered leukocytes. Flow cytometry revealed that microbubbles preferentially attached to activated leukocytes. Albumin microbubble attachment was inhibited by blocking the leukocyte beta(2)-integrin Mac-1, whereas lipid microbubble binding was inhibited when incubations were performed in complement-depleted or heat-inactivated serum rather than control serum. CONCLUSIONS: Microvascular attachment of albumin and lipid microbubbles in the setting of I-R and TNF-alpha-induced inflammation is due to their beta(2)-integrin- and complement-mediated binding to activated leukocytes adherent to the venular wall. Thus, microbubble persistence on contrast ultrasonography may be useful for the detection and monitoring of leukocyte adhesion in inflammatory diseases.

Albumins↗
PubMed2000

Assessment of resting perfusion with myocardial contrast echocardiography: theoretical and practical considerations.

BACKGROUND: The aim of this study was to perform a quantitative comparison between myocardial contrast echocardiography (MCE) and single-photon emission computed tomography (SPECT) in patients with prior myocardial infarction (MI). We also wanted to determine the optimal method for the intravenous administration of an ultrasound contrast agent in the clinical setting. METHODS AND RESULTS: Seventeen patients with resting perfusion defects in a single vascular territory on SPECT were studied. MCE was performed with intermittent harmonic imaging during continuous infusions of a second-generation ultrasound contrast agent (Sonovue, Bracco Diagnostics) in all 17 patients and after bolus injection in 8 of them. During continuous infusions, the video intensity (VI) ratio between the abnormal and normal myocardium at a pulsing interval (PI) of 8 cardiac cycles correlated well with the activity ratio between these segments on SPECT (r = 0.73, P <.01). When information regarding microbubble velocity (MV) denoted as change in VI with increasing PIs was added, the correlation with SPECT activity ratio improved (P <.05) significantly (r = 0.87, P <.0001). Higher microbubble doses resulted in higher VI during continuous infusions with good myocardial opacification and no far-field attenuation until the highest dose was reached. With bolus injections, the VI ratio between the abnormal and normal myocardium at PI of 1 and 5 cardiac cycles showed a modest correlation (r = 0.46 and r = 0.48, respectively, P <.05) with activity ratios between these regions on SPECT. When a dose of microbubbles administered as a bolus produced adequate myocardial opacification, it invariably resulted in far-field attenuation. CONCLUSIONS: In patients with prior MI, quantitative assessment of resting perfusion defects on MCE correlates well with regional activity on SPECT. Continuous infusions offer an advantage over bolus injections because they can provide an assessment of both relative VI and MV. Adjustment of the microbubble infusion rate produces adequate myocardial opacification without attenuation.

Coronary Circulation↗
PubMed1998

Albumin microbubble persistence during myocardial contrast echocardiography is associated with microvascular endothelial glycocalyx damage.

BACKGROUND: We hypothesized that the persistence of albumin microbubbles within the myocardium during crystalloid cardioplegia (CP) infusion and ischemia-reperfusion (I-R) occurs because of endothelial injury. METHODS AND RESULTS: The myocardial transit rate of albumin microbubbles was measured in 18 dogs perfused with different CP solutions and in 12 dogs undergoing I-R. Electron microscopy with cationized ferritin labeling of the glycocalyx was performed in 9 additional dogs after CP perfusion and in 3 additional dogs undergoing I-R. Microbubble transit was markedly prolonged during crystalloid CP perfusion. The addition of whole blood to the CP solution accelerated the transit rate in a dose-dependent fashion (P<0.05), which was greater with venous than with arterial blood (P<0.05). The addition of plasma or red blood cells to CP solutions was less effective in improving transit rate than addition of whole blood (P<0.05). Microbubble transit rate was independent of the temperature, K+ content, pH, PO2, osmolality, viscosity, and flow rate of the perfusate. Similarly, a proportion of microbubbles persisted in the myocardium after I-R, which was related to the duration of ischemia (P<0.01) but not of reflow. Crystalloid CP perfusion and I-R resulted in extensive loss of the endothelial glycocalyx without other ultrastructural changes. This effect was partially reversed in the case of crystalloid CP when it was followed by blood CP. CONCLUSIONS: Sonicated albumin microbubbles persist within the myocardium in situations in which the endothelial glycocalyx is damaged. The measurement of the myocardial transit rate of albumin microbubbles may provide an in vivo assessment of endothelial glycocalyx damage.

Animals↗
PubMed1998

Myocardial perfusion characteristics and hemodynamic profile of MRX-115, a venous echocardiographic contrast agent, during acute myocardial infarction.

We sought to determine whether MRX-115, a new venous echocardiographic contrast agent, could accurately assess risk area during coronary occlusion and infarct size after reperfusion by using novel imaging modalities meant to selectively enhance contrast signals. In 12 open-chest dogs, venous injections of 0.5 ml of MRX-115 were performed during baseline and coronary occlusion and after reperfusion in the presence of exogenous hyperemia. Ultrasound was transmitted at 2 MHz and received at both 2 MHz (fundamental) and 4 MHz (harmonic) frequencies during continuous and intermittent (end-systolic only) imaging. The risk area during coronary occlusion was compared with technetium autoradiography, and the infarct size after reperfusion was compared with postmortem tissue staining. MRX-115 produced no alterations in hemodynamic or pulmonary gas exchange at any stage. During continuous (both fundamental and harmonic) and intermittent fundamental imaging, measurements of perfusion defects were precluded in many dogs by either poor signal enhancement or posterior wall attenuation. By comparison, these measurements were possible during intermittent harmonic imaging in all dogs except one, which had a very small infarction during reflow. Correlation analysis between perfusion defect size on intermittent harmonic imaging and either autoradiographic risk area or postmortem infarct size gave r values of 0.83 and 0.92, respectively. We conclude that MRX-115 is hemodynamically well tolerated and, when imaging is performed after venous injection, can accurately assess regions of hypoperfusion when combined with intermittent harmonic imaging. These results are promising for the use of this approach in patients with acute myocardial infarction.

Animals↗
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↗