Secular trends in invasive meningococcal disease, Massachusetts, 1988-2011: what happened to invasive disease?

Invasive meningococcal disease (IMD) reported to the Massachusetts Department of Public Health from 1988 to 2011 was reviewed. The average annual incidence of IMD/100 000 decreased from 1·57 [95% confidence interval (CI) 1·42-1·73] for 1988-1991 to 0·22 (95% CI 0·17-0·29) for 2008-2011. The pattern of decreasing incidence over time differed by age group. There was a decrease in IMD/100 000 in the 0-4 years age group after 1991 from 10·92 (95% CI 8·08-14·70) in 1991 to 5·76 (95% CI 3·78-8·72) in 1992. Incidence in the 0-4 years age group remained below 5/100 000 per year on average thereafter. A substantial reduction in incidence in all age groups was observed between 2000 and 2009, which began before the introduction of conjugate meningococcal vaccine in 2005. Marked reductions in incidence of IMD in Massachusetts, and elsewhere, deserve further investigation with respect to potential factors that go beyond the introduction and deployment of improved meningococcal vaccines.

Pneumonia and influenza hospitalization in HIV-positive seniors.

HIV-positive persons and the elderly have increased risk for influenza-related complications, including pneumonia. Using claims data for pneumonia and influenza (P&I) hospitalization in the USA, we described the temporo-demographic trends and in-patient case-fatality in persons aged ≥ 65 years by HIV status. Our results showed a near doubling in the fraction of P&I admissions representing HIV-positive persons between 1991 and 2004 [relative risk (RR) 1·95, 95% confidence interval (CI) 1·80-2·13]. HIV-positive adults were younger (70·3 vs. 79·9 years, P<0·001), and had higher case-fatality (18·0% vs. 12·6%, P<0·001). Adjusting for other variables, case-fatality decreased by 5·8% in HIV-positive persons with the availability of highly active antiretroviral therapy (P=0·032). However, HIV-positive seniors were still 51% more likely to die during hospitalization than HIV-negative persons in 2004 (OR 1·51, 95% CI 1·23-1·85). HIV-infected persons represent a growing fraction of the elderly population hospitalized with P&I. Additional measures are needed to reduce case-fatality associated with P&I in this population.

Intracoronary gene transfer of fibroblast growth factor-5 increases blood flow and contractile function in an ischemic region of the heart.

Increased coronary blood vessel development could potentially benefit patients with ischemic heart disease. In a model of stress-induced myocardial ischemia, intracoronary injection of a recombinant adenovirus expressing human fibroblast growth factor-5 (FGF-5) resulted in messenger RNA and protein expression of the transferred gene. Two weeks after gene transfer, regional abnormalities in stress-induced function and blood flow were improved, effects that persisted for 12 weeks. Improved blood flow and function were associated with evidence of angiogenesis. This report documents, for the first time, successful amelioration of abnormalities in myocardial blood flow and function following in vivo gene transfer.

Ultrashort light pulses.

Experimental techniques are now available for the generation of repetitive and single coherent optical pulses of extremely short time duration and high peak power. These pulses should find extensive application in basic and applied research. Additional shortening of optical pulse durations can be obtained by means of the stimulated Raman effect, second-harmonic generation, or amplification with nonlinear laser amplifiers.

Comparison of real-time and intermittent triggered myocardial contrast echocardiography for quantification of coronary stenosis severity and transmural perfusion gradient.

BACKGROUND: Both intermittent triggered and real-time myocardial contrast echocardiography (MCE) have been proposed to detect impaired myocardial perfusion. We compared the ability of these 2 methods to quantify altered myocardial blood flow (MBF) and transmural distribution of MBF produced by graded coronary stenoses. METHODS AND RESULTS: In 8 open-chest dogs, we created 4 graded left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced adenosine hyperemia (non-flow-limiting at rest) and 1 grade of flow-limiting at rest. Real-time MCE was performed with SonoVue infusion using low-energy power pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI) was plotted versus time by real-time MCE and versus pulsing intervals by triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A) and the rate of SI rise (b). Visual detection of decreased opacification was equivalent by triggered and real-time MCE. Fluorescent microsphere-derived MBF ratio in LAD/left circumflex artery beds demonstrated close correlation with both real-time imaging (b, r=0.79; Axb, r=0.81) and triggered imaging (b, r=0.78; Axb, r=0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated closer correlation with the endocardial/epicardial ratios of b (r=0.71) and Axb (r=0.67) obtained by real-time than triggered imaging (b, r=0.42; Axb, r=0.52). CONCLUSIONS: Real-time and triggered MCE are equivalent in their ability to identify coronary stenosis and quantify altered MBF.

Assessment of coronary stenosis severity and transmural perfusion gradient by myocardial contrast echocardiography: comparison of gray-scale B-mode with power Doppler imaging.

BACKGROUND: The present study (1) compared the ability of power Doppler imaging with that of gray-scale B-mode tissue imaging to opacify the myocardium and detect coronary stenosis by myocardial contrast echocardiography and (2) compared the response of video intensity (VI) to variable pulsing intervals for each modality. METHODS AND RESULTS: Four grades of left anterior descending coronary artery (LAD) stenoses were created in 9 open-chest dogs. Stenoses reduced resting LAD flow by 25%, 50%, 75%, and 100% of baseline by flow probe. Myocardial contrast echocardiography was performed during varying ECG gated pulsing intervals (PIs) from 1:1 to 1:10. By gray-scale imaging, background-subtracted LAD bed VI was less than baseline VI at all PIs for the 100% reduced-flow state but not for any other flow state or interval. By power Doppler imaging, LAD bed VI was less than baseline VI at all intervals for 75% and 100% reduced-flow states but only 1:1 and 1:2 for 25% and 50% reduced-flow states, respectively. Correlation of VI and myocardial blood flow (determined by use of fluorescent microspheres) ratios from stenosed versus normal beds was stronger by power Doppler imaging. A transmural opacification gradient with stenosis was visualized and measured by power Doppler imaging, but it was insignificant by gray-scale imaging. The ratio of endocardial/epicardial flow determined by use of fluorescent microspheres was correlated with VI by power Doppler imaging at all PIs. CONCLUSIONS: Power Doppler imaging has advantages compared with gray-scale imaging in opacifying the myocardium and in detecting coronary stenosis and altered transmural distribution of myocardial perfusion from peak VI. Because VI differences from baseline at long PI vary for mild versus severe (75% and 100%, respectively) reduced-flow states, power Doppler imaging may provide a method to quantify coronary stenoses.

Comparative value of dobutamine and adenosine stress in the detection of coronary stenosis with myocardial contrast echocardiography.

BACKGROUND: Controversy continues as to whether adenosine or dobutamine is the superior pharmacological stress agent for myocardial contrast echocardiography (MCE). METHODS AND RESULTS: We compared real-time MCE refilling curves and wall thickening during adenosine and dobutamine stress in 14 open-chest dogs with left anterior descending and left circumflex coronary artery stenoses that reduced hyperemia by 40% to 60% and 70% to 90% (mild and severe non-flow-limiting stenosis, NFLS) and resting flow by 10% to 30% and 35% to 50% (mild and severe flow-limiting stenosis, FLS). MCE was performed with low-energy imaging during Optison infusion. After high-energy bubble destruction, time-intensity data from risk beds were fitted for an exponential function as y=A(1-e(-)(bt)), from which the rate of intensity increase (b) and maximal plateau intensity (A) were derived. Although severe NFLS and greater stenoses decreased b with both dobutamine and adenosine, with mild NFLS it was reduced in 58% of animals with dobutamine versus 8% with adenosine. The absolute decrease in b, however, was greater for adenosine than dobutamine with FLS. The A parameter was decreased with both adenosine and dobutamine only with the most severe FLS. Wall thickening was decreased with dobutamine in 33% of animals with severe NFLS and in all animals with any FLS; with adenosine, in all with severe FLS. CONCLUSIONS: Both dobutamine and adenosine significantly reduce MCE refilling rates in the setting of severe stenosis and in the absence of contractile abnormalities. Dobutamine decreases refilling rate and wall thickening at a less reduced flow grade than adenosine, but adenosine produces a greater magnitude of change than dobutamine.

Assessment of myocardial postreperfusion viability by intravenous myocardial contrast echocardiography: analysis of the intensity and texture of opacification.

BACKGROUND: Although defects on intracoronary myocardial contrast echocardiography (MCE) indicate loss of viability after reperfusion, opacified segments may also exhibit persistent dyssynergy. Therefore, we related the intensity and texture of opacification produced by an intravenous contrast agent to histological findings to determine the characteristics of necrotic tissue by postreperfusion MCE. METHODS AND RESULTS: MCE was performed by intravenous injection of 0.15 mL/kg QW7437 in 14 dogs who underwent 3-hour coronary occlusion followed by 3-hour reperfusion. At baseline and 3 hours after reperfusion, midventricular short-axis images were digitized and segmented. Infarction fraction (IF) for each segment was determined by triphenyltetrazolium chloride stain. Of 224 segments, 140 showed no or small infarction and served as a control group. Of 84 segments with significant infarction (IF>30%), 52 exhibited a defect on MCE, and 32 exhibited no defect. Echo texture was quantified by computing entropy based on the co-occurrence matrix analysis of gray-level pairs within each segment. Three hours after reperfusion, average and maximal entropies in the infarct segments without opacification defects were significantly higher than control levels. Histologically, the degree of intracapillary erythrocyte stasis was less in this group than in the infarcted segments with MCE defects with similar magnitude of tissue injuries. CONCLUSIONS: Opacification defects by MCE may be present or absent in myocardium with histologically confirmed infarction. The texture of MCE from opacified but infarcted myocardium differed significantly from control segments and may assist in determination of segmental viability after reperfusion.

Ischemia-reperfusion injury at the microvascular level: treatment by endothelin A-selective antagonist and evaluation by myocardial contrast echocardiography.

BACKGROUND: The purpose of this study was to verify whether endothelin A-antagonist administration at the time of coronary reperfusion preserves postischemic microvasculature and whether myocardial contrast echo (MCE) is able to detect pharmacologically induced changes in microvascular reflow. METHODS AND RESULTS: Twenty dogs underwent 90 minutes of LAD occlusion (OCC) followed by 180 minutes of reperfusion (RP). Five minutes before LAD reopening, an intravenous bolus (5 mg/kg) of LU 135252 was given in 10 dogs and vehicle in the remaining 10. At baseline (BSL), OCC, and 90 and 180 minutes of RP, microvascular flow (BF) was assessed by microspheres, and MCE was performed with intravenous echo contrast. MCE videointensity and BF were expressed as risk area/control ratio. Myocardial thickness of the risk area was calculated by 2D echo. No differences in BF between the 2 groups were observed at BSL, OCC, and 90 minutes of RP. At 180 minutes of RP, BF was decreased in controls (70+/-7.4% of BSL; P:<0.005 versus BSL) and preserved in LU 135252-treated animals (89+/-4% of BSL; P=NS versus BSL; P<0.05 versus controls). Videointensity at MCE closely followed the changes in BF observed in both groups throughout the protocol. Myocardial thickness at 180 minutes of RP increased to 138.6+/-9.9% of BSL in controls and remained at 108.9+/-7.4% of BSL in treated dogs (P<0.05). CONCLUSIONS: Endothelin A-antagonist treatment at the time of reperfusion significantly limited the progressive decrease in postischemic microvascular reflow and the increase in myocardial thickness. MCE allowed a reliable evaluation of pharmacologically induced changes in microvascular flow.

Optimal utilization of thrombolytic therapy for acute myocardial infarction: concepts and controversies.

Timely administration of thrombolytic therapy decreases myocardial infarct size, lessens the incidence of congestive heart failure and improves survival. However, available data suggest that only 10% of patients with acute infarction in the United States receive thrombolytic drugs. Given the benefits of thrombolytic therapy, all patients with myocardial infarction would likely be treated were it not for associated risks. Several groups exist in which the risk/benefit ratio of thrombolytic therapy continues to be controversial, including those with inferior infarction, absence of ST segment elevation or presentation greater than 6 h from symptom onset, elderly patients and those with hypertension. Three recent thrombolytic trials reported a reduction in mortality that was entirely independent of infarct location. Pooled data from trials involving 12,000 patients with inferior infarction have demonstrated a reduction in mortality rate (6.8% versus 8.7%, p less than 0.0001). Furthermore, improvement in regional and global left ventricular function occurred after reperfusion therapy of inferior infarction. Pooled data indicate that patients treated between 6 and 24 h after symptom onset have a lower mortality rate than do those who receive placebo (11.1% versus 13.1%, p less than 0.001). Improved survival occurs after thrombolytic therapy in patients with ST segment elevation or left bundle branch block, but not in those with isolated ST depression or a normal electrocardiogram. Age should not be considered an absolute contraindication because the lifesaving potential of thrombolytic therapy in the elderly may be two to three times that of the overall group of patients with myocardial infarction. Finally, recent studies demonstrated that patients who present with hypotension or hypertension or who have undergone cardiopulmonary resuscitation may also benefit.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial contrast echo effect: the dilemma of coronary blood flow and volume.

Despite the useful information provided by myocardial contrast echocardiography, the meaning of myocardial contrast intensity remains elusive. This review is meant to define the contribution of physical and biologic factors in producing myocardial contrast and to elucidate the relative roles of coronary blood flow and intramyocardial blood volume in determining contrast effect. The main physical factors influencing the contrast echo effect include the properties of microbubbles as scattering elements (mainly their radius, compressibility, stability and concentration), electronic signal processing, instrument setting and contrast-induced signal attenuation. The effect of these factors can be limited by an appropriate experimental or clinical setup. Biologic factors are less easily controllable, and changes in coronary blood flow and alterations in myocardial blood volume appear to be the main determinants of myocardial contrast intensity. Moreover, these factors influence contrast intensity in opposite directions. Both the area under the time-intensity curve and the mean transit time of myocardial contrast are inversely related to coronary blood flow but directly related to myocardial vascularity and blood volume. Therefore, an increase in coronary flow not accompanied by an increase in myocardial vascularity and volume is accompanied by a decrease in the area under the curve and mean transit time of contrast. Conversely, an increase in coronary flow mediated by augmented myocardial vascularity and volume will produce an increase in the area under the curve and mean transit time. A better understanding of the physical and biologic determinants of contrast echo intensity will be fundamental in the clinical application of new agents and technologies.

Left ventricular distensibility and passive elastic stiffness in atrial septal defect.

Diminished left ventricular distensibility has been postulated as a cause of left ventricular failure in atrial septal defect. To evaluate this hypothesis the indexes of left ventricular compliance and stiffness were estimated in 15 patients with atrial septal defect and the results compared with those in 10 normal subjects. Age, peak left ventricular systolic pressure, end-diastolic pressure, ejection fraction and cardiac index did not differ significantly between groups. Left ventricular end-diastolic volume for the atrial septal defect group was significantly less than that for the control group (mean +/- SD, 61 +/- 9 ml/m2 versus 73 +/- 13, p less than 0.05) in keeping with previous studies. The slope of the log pressure-volume relation was significantly greater in the group with atrial septal defect than in the normal group (0.056 +/- 0.010 versus 0.044 +/- 0.008, p less than 0.01), consistent with increased chamber stiffness. For a group of six patients with atrial septal defect and elevated left ventricular end-diastolic pressure, normalized compliance was significantly less than that in the control group (0.017 +/- 0.001 versus 0.036 +/- 0.007, p less than 0.02). The slope k of the elastic stiffness-stress relation for the total group with atrial septal defect was significantly greater than that of the normal group (21.0 +/- 2.3 versus 18.1 +/- 2.3, p less than 0.01). An index of muscle fiber stretch (dV/VdP x end-diastolic stress x 100) was significantly less in the atrial septal defect group than in the control group (74 +/- 24 versus 106 +/- 22, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Uses and limitations of exercise Doppler echocardiography in the diagnosis of ischemic heart disease.

This study tested the hypothesis that coronary artery disease might be identified by a decrease in Doppler measurements of flow velocity and acceleration. The response of aortic blood flow velocity and acceleration to exercise was determined in 102 subjects (28 young control subjects and 74 older patients) who underwent continuous wave Doppler echocardiographic examination before, during and immediately after near maximal treadmill exercise. Patients were grouped according to the results of thallium perfusion imaging: Group I = normal, Group II = ischemia with or without prior infarction and Group III = prior infarction only. A significant decrease in the level of velocity and acceleration achieved with exercise was observed both in patients in Group I (normal thallium study) (1.2 +/- 0.3 m/s and 36.8 +/- 14 m/s per s, p less than or equal to 0.005) and in patients in Group II (ischemia) (1.1 +/- 0.3 m/s and 27.7 +/- 11 m/s per s, p less than or equal to 0.0005) compared with values in young control subjects (1.4 +/- 0.2 m/s and 52.7 +/- 16 m/s per s). When groups of patients of similar age who differed in the presence (Group II) or absence (Group I) of ischemia on thallium scintigraphy were compared, no difference was found for maximal velocity (1.1 +/- 0.3 versus 1.2 +/- 0.3 m/s, p = NS), but acceleration was significantly lower in Group II (27.7 +/- 11 versus 36.8 +/- 14 m/s per s, p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Observer variability in the quantitation of Doppler color flow jet areas for mitral and aortic regurgitation.

Early studies using Doppler color flow imaging have suggested that measurement of the regurgitant jet area provides information regarding the severity of valvular insufficiency. This study was performed to assess the observer variability of mitral and aortic regurgitant jet area measurements using the Doppler color technique. Color Doppler recordings from 45 patients were reviewed: 23 patients had aortic regurgitation and 22 had mitral regurgitation. To assess interobserver variability, the largest definable mitral regurgitant jets from three cardiac cycles were independently chosen and measured by planimetry by two observers who were unaware of other patient information. Measurements were repeated by both observers at a separate time to obtain intraobserver data. Videotapes from 23 patients with aortic regurgitation were similarly analyzed. Each observer measured the isovolumic aortic jet (before mitral valve opening) and the maximal aortic regurgitant jet (at any time during diastole) using computer-assisted planimetry. Both intraobserver and interobserver correlations were excellent for mitral regurgitant jet areas (r = 0.97 and r = 0.93, respectively). The intraobserver correlation for isovolumic aortic regurgitant jet was r = 0.73; the interobserver correlation for this measurement was only fair (r = 0.57). For the maximal aortic regurgitant jet area, intraobserver correlation was good (r = 0.86) and interobserver correlation was fair (r = 0.72). These findings suggest that intraobserver and interobserver reproducibility are acceptable for the measurement of mitral regurgitant jet area.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of ventricular tachycardia using an automatic scanning extrastimulus pacemaker.

A patient with recurrent sustained ventricular tachycardia that was resistant to both conventional and experimental antiarrhythmic agents was treated with a programmable automatic scanning extrastimulus pacemaker. The antitachycardia pacemaker was implanted only after many episodes of spontaneous and laboratory-induced ventricular tachycardia were reliably and reproducibly terminated with programmed ventricular extrastimuli. In the 6 months since implantation of the automatic scanning pacemaker, all episodes of ventricular tachycardia have been terminated successfully by the pacemaker. Acceleration of rate of ventricular tachycardia or induction of ventricular fibrillation did not occur at any time during attempted termination of ventricular tachycardia by the pacemaker. The advantages of the automatic scanning extrastimulus pacemaker over other antitachycardia pacemakers are discussed.

Superior intensity and reproducibility of SHU-454, a new right heart contrast agent.

Intravenous injection of a variety of fluids has been shown to produce right heart contrast by ultrasound, but the intensity and reproducibility achieved are variable. Thus, a new polysaccharide agent being developed for commercial distribution, SHU-454, was quantitatively compared for intensity and variability with agitated saline solution, indocyanine green, carbon dioxide and hydrogen peroxide. Videodensitometry was used to measure peak and total opacification of the right ventricle after peripheral intravenous contrast administration. One hundred eighty injections were performed in nine closed chest dogs while two-dimensional echograms were recorded. SHU-454 yielded the highest peak (p less than 0.001) and total (p less than 0.005) intensity values when compared with the standard agents. In addition, SHU-454 yielded the lowest coefficient of variation between injections (p less than 0.04) in producing this contrast effect. There were no biologically significant changes in heart rate, blood pressure or arterial blood gases during injection of any of the substances used. A newly developed agent, SHU-454, is superior to standard agents in the ability to reliably produce right heart contrast after venous injection in dogs.

Influence of operator- and patient-dependent variables on the suitability of automated quantitative coronary arteriography for routine clinical use.

This study was designed to elucidate the operator- and patient-dependent variables inherent in clinical application of quantitative coronary arteriography. Digital arteriograms from 25 consecutive patients undergoing diagnostic catheterization were analyzed by four experienced angiographers utilizing an automated coronary edge detection system to measure percent area stenosis. The identification of potentially significant lesions for quantitation constituted a major source of variability, with unanimous agreement on the presence of a greater than or equal to 50% stenosis occurring at 38 (29%) of the 130 reported sites. Selection of an optimal frame for quantitative analysis resulted in disagreement for every lesion reported. Frame selection by the operator, as opposed to measurement of preselected frames, increased the interobserver variability from 5% to 7% for automated geometric analysis (p less than 0.01), and from 8% to 10.5% for automated densitometric analysis (p less than 0.01). Fully automatic arterial border detection was possible for only 20 (52.5%) of the 38 unanimously identified stenoses. The 18 failures involved one or more of the following factors: 1) stenosis at a bifurcation (13 [72%]); 2) diffuse, severe disease (8 [44%]); 3) excessive vessel tortuosity or overlap or both (4 [22%]); and 4) poor image quality (5 [28%]). In contrast, the same automated border detection algorithm successfully traced all 15 preselected frames of discrete stenoses referred for coronary angioplasty. Automated quantitative coronary arteriography performs well when carefully selected, discrete stenoses are presented to the computer for analysis. However, quantitative analysis of routine clinical coronary arteriograms is limited by operator-dependent variability in stenosis identification and frame selection, as well as by complex coronary anatomy and suboptimal image quality. These limitations make automated quantitative coronary arteriography impractical for routine clinical use.

Cardiovascular disease in the elderly. Clinical assessment.

The elderly patient with suspected cardiovascular disease poses a diagnostic challenge to the clinician. In many elderly patients the frequent unreliability of the history and the presence of multiple concurrent diseases and medications complicate accurate assessment of the patient's cardiac problem. Clinical laboratory and noninvasive cardiac techniques are now available that enhance the accuracy of cardiac diagnosis and aid in the evaluation of left ventricular function.

Comparison of magnetic resonance imaging and echocardiography in determination of cardiac dimensions in normal subjects.

No data exist regarding the ability of magnetic resonance imaging to assess cardiac size and performance in human beings. Therefore, measurements of cardiac dimensions by magnetic resonance imaging were compared with those obtained by two-dimensional echocardiography in 21 normal subjects. Magnetic resonance transverse cardiac sections were obtained during electrocardiographic gating using a spin echo pulse sequence. In normal subjects, magnetic resonance imaging yielded a range of values for cardiac dimensions having a similar standard deviation as that of two-dimensional echocardiography. Diastolic measurements of the aorta, left atrium, left ventricle and septum obtained by magnetic resonance imaging correlated well with those obtained by two-dimensional echocardiography (r = 0.82, 0.78, 0.81 and 0.75, respectively). The correlation coefficient of r = 0.35 observed for the posterior wall thickness was not surprising in view of the narrow range of normal values. Only a general correlation (r = 0.53) existed for the right ventricular diastolic dimension; this was probably related to the difficulty in obtaining representative measurements due to the complex geometry of this chamber. Failure of systolic dimension measurements by magnetic resonance imaging to correlate with those obtained by echocardiography is probably related to limitations of electrocardiographic gating, especially of determining the exact end-systolic frame. Although technically complex at present, magnetic resonance imaging does provide an additional noninvasive technique for measurement of cardiac size.

Flow dynamics of QW7437, a new dodecafluoropentane ultrasound contrast agent, in the microcirculation: microvascular mechanisms for persistent tissue echo enhancement.

OBJECTIVES: The purpose of this study was to test the hypothesis that a subgroup of QW7437 microbubbles, dodecafluoropentane-based ultrasound contrast microspheres, resides for prolonged periods in the microvasculature. BACKGROUND: QW7437 produces echo enhancement in myocardium which may persist relatively longer than opacification in the left ventricular cavity. The mechanism for this persistent enhancement remains unknown. METHODS: The transit of fluorescently labeled erythrocytes was examined by fluorescence intravital microscopy in the microvessels in five rat mesenteries. Ten rats were used to observe the behavior of fluorescently labeled QW7437 microbubbles in the mesenteric microcirculation. RESULTS: There was no significant change in erythrocyte velocity in the arterioles and venules after the administration of QW7437 microbubbles (0.05 ml/kg) preactivated by negative hydrodynamic pressure. Of 552 microbubbles observed in four arterioles and five capillaries, 549 (99.5%) passed without stoppage (> or = 0.1 s stoppage); only one stopped transiently in arteriole and two in capillaries, each for <0.5 s. Sixty-five of 478 microbubbles (13.6%) observed in six postcapillary venules 11 to 30 microm in diameter and 24 of 408 microbubbles (5.9%) in four venules 31 to 50 microm in diameter stopped transiently (0.1 to 180 s) with an attachment to venular endothelium; the remaining microbubbles passed through the venules without stoppage. CONCLUSIONS: Prolonged survival as microbubbles in the circulation and transient stoppage of a subgroup of microbubbles in the microvasculature, particularly in venules, are potential mechanisms for the persistent tissue echo enhancement by QW7437 microbubbles during contrast echocardiography.