Intracoronary air-filled albumin microspheres for myocardial blood flow measurement.

OBJECTIVES: The aim of this study was to explore the possibility of quantifying coronary blood flow by myocardial contrast echocardiography with air-filled serum albumin microspheres (Albunex). BACKGROUND: Air-filled albumin microspheres have been proposed as an intravascular tracer for the study of myocardial perfusion by contrast echocardiography. METHODS: In six anesthetized open chest dogs, the left circumflex coronary artery was cannulated and perfused by a roller pump with blood from the femoral artery. Both air-filled albumin microspheres (0.4 ml, 2 x 10(8) spheres/ml) and technetium-99m-labeled albumin were injected as a bolus into the coronary cannula at baseline and after treatment with dipyridamole (0.56 mg/kg body weight intravenously for 4 min). Two-dimensional echographic images of the left ventricular short axis were digitized to generate myocardial time-intensity curves; myocardial radioactivity was measured by an external detector to generate radionuclide time-activity curves. RESULTS: After dipyridamole, left circumflex coronary artery blood flow (as measured by both the pump and an electromagnetic flow meter) significantly increased (from 1.06 +/- 0.28 to 3.61 +/- 1.43 ml/min per g of myocardium). Peak intensity and rise time of contrast echo curves were able to differentiate baseline myocardial perfusion from coronary hyperemia but did not show any significant correlation with coronary blood flow. A weak inverse correlation with coronary blood flow was provided by myocardial mean transit time of air-filled albumin microspheres (r = 0.33). Conversely, a close inverse correlation with coronary blood flow was obtained by myocardial mean transit time of technetium-99m-labeled albumin (r = 0.95). Myocardial transit time of air-filled albumin microspheres (1.95 +/- 0.60 s) was also markedly shorter than that of labeled albumin (5.35 +/- 3.43 s, p < 0.001) and the measurements were less reproducible. CONCLUSIONS: In this experimental study, coronary blood flow was not adequately quantified by myocardial contrast echocardiography with intracoronary injection of air-filled albumin microspheres.

Myocardial washout of sonicated iopamidol does not reflect the transmural distribution of coronary blood flow.

It has been shown in previous studies that myocardial contrast echocardiography provides quantitative information on coronary blood flow. However, the ability of contrast echo to assess the transmural (endo/epicardial) distribution of blood flow is still debated. To test this hypothesis, the left circumflex coronary arteries of six anaesthetized open-chested dogs were cannulated and perfused with blood from the femoral artery. At different rates of coronary blood flow, during adenosine-induced coronary vasodilation, sonicated iopamidol and radionuclide labelled microspheres were injected into the coronary cannula, immediately proximal to a mixing chamber. Two-D echo images were digitized and myocardial time-intensity curves were obtained for the endocardial, mid- and epicardial layers. A good correlation existed between contrast washout of the entire ventricular wall and coronary flow (r = 0.85). However, the washout rate from the endo-, mid- and epicardial layers showed weak correlations with corresponding regional blood flows measured by microspheres (r = 0.56, 0.71 and 0.58, respectively). No significant relationship was found between the endo/epicardial washout ratio and the corresponding flow ratio by microspheres. Thus, measurement of the transmural distribution of coronary blood flow by myocardial contrast echocardiography remains an elusive goal.

Flow quantitation by contrast echocardiography. Effects of intervening tissue and of the angle of incidence between flow and ultrasonic beam.

The combination of a standardized echographic contrast agent with the analysis of the ultrasonic radio frequency (RF) signal allowed in vitro flow quantitation in a circulation model. The purpose of this study was to investigate both the effects of biological tissues, intervening between probe and insonated structure, and the effects of the angle of incidence between flow and ultrasonic beam on RF flow quantitation. Thus, the contrast agent SHU 454 was intravenously injected (0.4 ml) as a bolus into a circulation model, at variable flow rates, while keeping the pressure and volume of the vessel constant. Injections were performed with saline interposed between probe and vessel and after the addition of the subcutaneous tissue of a pig; injections were also performed using the probe normal to the flow and with an angle of incidence of 45 degrees. Echographic data were recorded by a mechanical sector scanner, capable of sampling the RF signal from a region of interest positioned in the center of the vein. Contrast echo time-intensity curves were generated. As expected, both peak intensity and the area under the curves decreased with intervening tissue (-58 and -70% of baseline values, respectively, p < 0.001). Surprisingly, mean transit time also decreased with intervening tissue (from 1.12 +/- 0.25 seconds with saline, to 0.92 +/- 0.13 seconds with tissue, p < 0.001), thus producing a systematic overestimation of flow (21% on the average). To compensate for signal attenuation, contrast injections were repeated in the presence of tissue after increasing the electronic signal amplification (10 dB), and transit time did not significantly differ from control.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of coronary blood flow on myocardial grey level amplitude in two dimensional echocardiography: an experimental study.

OBJECTIVE: The aims were: (1) to evaluate whether differences in absolute and cyclic echocardiographic image amplitude exist in different layers (subendocardium and subepicardium) and regions (septal, anterior, lateral, inferior wall) of the canine left ventricle; (2) to assess the dependence of these variables upon local variations of coronary blood flow. METHODS: In six anaesthetised open chest dogs the circumflex coronary artery was cannulated and perfused by a roller pump with blood from their own femoral artery. Maximum coronary vasodilatation was obtained by continuous adenosine infusion. The absolute values and the transmural distribution of coronary blood flow were measured by radionuclide labelled microspheres. Echo images were obtained in short axis view by a commercially available electronic sector scanner with a 5.0 MHz transducer directly placed on the epicardial surface of the right ventricle, and digitised off-line into a matrix of 256 x 256 pixels with 25% grey level per pixel. The average grey level was calculated for each region of interest. RESULTS: In 32 different conditions, circumflex flow ranged from 0.80 to 12.89 ml.min-1.g-1 and the endocardial/epicardial ratio of flow from 0.53 to 1.73. In the circumflex region (subjected to flow changes) segmental amplitude varied from 76(SD 20) (end diastole) to 56(18) (end systole), p < 0.001. In all regions, a consistent cyclic variation was found, ranging from 9(14) to 28(16)%. For all levels of flow, subendocardial and subepicardial regions showed similar values of both absolute amplitude and cyclic variation. No significant relationship was found between transmural distribution of blood flow and either segmental amplitude (r = 0.26) or cyclic variation (r = 0.04). CONCLUSIONS: (1) a consistent cyclic grey level variation is present in all regions of the canine left ventricle, but subendocardial and subepicardial layers show similar values of both absolute amplitude and cyclic variation; (2) in the absence of severe underperfusion and echocardiographically detectable dyssynergy, absolute amplitude and cyclic variation are totally unrelated to changes in coronary blood flow.

Myocardial washout of sonicated iopamidol reflects coronary blood flow in the absence of autoregulation.

OBJECTIVES: The aim of the study was to evaluate the relation between measurements derived from myocardial contrast echocardiography and coronary blood flow. BACKGROUND: Contrast echocardiography has the potential for measuring blood flow. METHODS: In six open chest anesthetized dogs, the left circumflex coronary artery was cannulated and perfused with blood drawn from the left femoral artery. While adenosine was infused into the circuit, circumflex flow was generated by a calibrated roller pump to the point of abolishing coronary autoregulation. At each of 25 levels of coronary blood flow, paired bolus injections of sonicated iopamidol were performed proximal to a mixing chamber. The perfused area of the left circumflex coronary artery was labeled by radioactive microspheres injected into the perfusion line. Two-dimensional echocardiographic images of the left ventricular short axis were digitized off-line, and myocardial videodensity was measured in the area perfused by the left circumflex coronary artery to generate time-intensity curves. RESULTS: The washout slope of curves showed a good correlation with coronary blood flow, ranging from 0.5 to 12.5 ml/min per g of tissue. This correlation was good both in individual dogs (correlation coefficient [r] ranging from 0.78 to 0.96) and in the group of animals as a whole (r = 0.85). Washout slope also showed a good correlation with coronary diastolic pressure (r = 0.80), which ranged from 23 to 114 mm Hg, suggesting a possible primary effect of pressure on contrast washout. However, coronary blood flow appeared to be a stronger predictor of washout slope (partial F = 26.5, p < 0.001) than did perfusion pressure (partial F = 5.9, p < 0.05 by multiple regression). The injection to injection variability in myocardial washout slope appeared to be high (24%). The gamma variate fitting of curves did not improve the correlation with coronary flow (r = 0.78). CONCLUSIONS: Myocardial washout of sonicated iopamidol reflects coronary blood flow in a model in which coronary autoregulation is abolished.

Discordance between responses of contrast echo intensity to increased flow rate in human coronary circulation and in vitro.

According to the Stewart-Hamilton equation flow is inversely related to the area under the time-concentration curve produced by the transit of a detectable indicator. To verify the applicability of this principle for contrast echocardiography, we bolus injected a saccharide echo contrast agent (0.8 ml) into an in vitro circulatory model at variable flow rates. Two-dimensional echo images were digitized, and curves demonstrating the ratio of videointensity over time were derived. As expected, flow was inversely related to the area under the curves (r = 0.93). To apply this principle to human coronary circulation, we bolus injected sonicated iopamidol (4 ml) into the normal left coronary artery of six patients at baseline and after intravenous administration of dipyridamole (0.84 mg/kg in 10 minutes). Echo images were digitized, and myocardial time-intensity curves were derived. The area under the curve after dipyridamole administration (210 +/- 128 gray level.sec) did not appear significantly different from that at baseline (177 +/- 80 gray level.sec). Thus a mismatch exists between contrast echo data obtained in vitro and in human coronary circulation.

Correlations between 15 polycyclic aromatic hydrocarbons (PAH) and the mutagenicity of the total PAH fraction in ambient air particles in La Spezia (Italy).

Airborne particulate matter has been monitored 4 times a month for 1 year (1988) in the city of La Spezia (Italy). The polycyclic aromatic hydrocarbon (PAH) fractions were extracted, purified and characterized for the content of 15 individual PAH. In general when concentrations of individual PAH were compared statistical correlation was obtained. Mutagenicity studies were performed by the use of the Ames plate test with the Salmonella strains TA98, TA100, TA98NR and TA98DNP6 with and without metabolic activation (S9 mix). The TA98 strain was by far the most responsive and the S9 mix was absolutely required as expected when PAH are assayed. Besides mutagenicity, toxicity was also considered and it proved to be correlated with mutagenicity in TA98, +S9. The TA98NR and TA98DNP6 strains showed no appreciable differences from the parental strain TA98 indicating the absence of significant amounts of direct-acting nitro derivatives in our PAH samples. Of the 15 PAH considered in this study the amounts of cyclopental[c,d]pyrene (CPP) correlated best with mutagenicity. The role of CPP in contributing to the indirect mutagenicity of urban air PAH samples is discussed.

Benzene and the genotoxicity of its metabolites. II. The effect of the route of administration on the micronuclei and bone marrow depression in mouse bone marrow cells.

Benzene (880 mg/kg) and 4 of its metabolites, i.e., phenol (265 mg/kg), hydroquinone (80 mg/kg), catechol (40 mg/kg), and p-benzoquinone (5-20 mg/kg) have been tested for their capability to induce micronuclei in bone marrow cells of male mice after oral administration or intraperitoneal injection. Oral administration of benzene shows more activity than intraperitoneal injection, whereas the metabolites show more activity if administered by the latter method. The respective genotoxic strengths of the benzene metabolites are the following: hydroquinone much greater than phenol greater than catechol = p-benzoquinone. This last is active when administered orally.