Adenosine and angiotensin system interact in the regulation of renal microcirculation in humans.

We sought to evaluate the possible interaction between the adenosine and angiotensin systems in the regulation of renal microcirculation in humans. Twenty normotensive patients entered the study. Ten patients (group 1) were pretreated with 50 mg of captopril, an inhibitor of angiotensin-converting enzyme, whereas 10 patients (group 2) were pretreated with placebo. Incremental doses of adenosine (from 10(-5) to 1 mg) were injected into a renal artery to all patients at 5-min intervals. Adenosine injection reduced mean renal blood flow velocity in both groups (from 17.3+/-2.8 and 16.7+/-2 cm/s to 5.1+/-1.1 and 3.8+/-0.8 cm/s, in groups 1 and 2, respectively). The decrease in flow velocity was immediate after adenosine, and its duration was proportional to dosage (y = 3.05 x -2.7; R2 = 0.46; p < 0.01). However, group 1 had a slope of regression lower than group 2 (2.37 vs. 3.82 s; p < 0.03). The index of renal resistance (mean arterial pressure/mean blood flow velocity) increased linearly in both groups with adenosine, but group I showed a lower slope of increment (2.77 vs. 5.57 mm Hg/cm/s; p < 0.01). Adenosine administration induced a marked and transient increase in human renal resistance. This vasoconstrictive effect of adenosine was blunted by captopril pretreatment.

Quantitative aspects in myocardial contrast echocardiography.

Myocardial tissue perfusion is not currently quantified in the clinical setting. Thus the aim of this paper is to review the quantitative information on myocardial perfusion provided by contrast echocardiography. In a circulatory model-without the capillary network interposed between injection and sampling point of contrast-the transit time of microbubbles (source of the echo contrast effect) is inversely related to absolute flow, thus providing accurate quantitation. A similar situation is represented by blood flow inside a vessel or a cardiac cavity, where, if the prerequisites for quantitation are respected, it is possible to measure blood flow by contrast echocardiography. In the coronary circulation, the transit time of contrast microbubbles varies according to their interaction with coronary microcirculation, and to the characteristics of contrast agents as flow tracers. Echo contrast agents with small microbubbles have been injected into the coronary branches of experimental animals, under both coronary autoregulation and maximal coronary dilation, providing good estimates of coronary blood flow. The accuracy of these measurements might improve when new contrast agents, with characteristics closer to those of a flow tracer, are available. If a tracer is injected before a bifurcation, and provided it mixes adequately, the amount of tracer distributed to each branch is proportional to the corresponding blood flow. A similar situation is encountered when an echo contrast agent is injected into the aortic root or into the left main coronary artery. Here, the ratio between myocardial signal intensity in the different perfusion territories reflects the corresponding ratio of blood flows. The validity of this approach has been previously demonstrated in experimental animals and validated in patients with coronary stenoses. The injection of contrast agents into the coronary circulation at baseline and under coronary hyperaemia has the potential for measuring coronary blood flow reserve. However, what is still unclear is whether contrast echo changes reflect changes in coronary blood flow (i.e. flow reserve), coronary blood volume (i.e. coronary recruitment) or both, and also whether they influence the different types of contrast agent. Finally, myocardial contrast echocardiography can provide information on the spatial distribution of myocardial perfusion, i.e. the presence, site and extent of perfused myocardium. Thus, in models where myocardial perfusion may be either present or absent, contrast echo can provide an accurate estimate of perfusion abnormalities.

Regression of hypertensive myocardial hypertrophy does not affect ultrasonic myocardial reflectivity: a tissue characterization study.

OBJECTIVE: Ultrasonic backscatter from the myocardial walls is directly related to the morphometrically or biochemically evaluated collagen content in man, and shows a normal pattern of quantitatively assessed ultrasonic backscatter in hypertensive patients, even in the presence of left ventricular hypertrophy. Whether the pharmacologically induced regression of left ventricular hypertrophy in hypertensive patients is accompanied by a disproportionate increase in relative connective tissue content is not yet known. The objective of the present study was to assess the effects of regression of left ventricular hypertrophy on the quantitatively evaluated myocardial reflectivity in essential hypertensives. DESIGN: We evaluated 19 mild-to-moderate essential hypertensives with echocardiographically assessed left ventricular hypertrophy, before and after 8 months' effective antihypertensive therapy with 20-40 mg enalapril once a day, associated with diuretics or calcium antagonists, or both, in six patients to achieve optimal blood pressure control. Using a modified echo machine developed in the Institute of Clinical Physiology, Pisa, an on-line radio-frequency analysis was performed to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and the posterior wall. The integrated values of the radio-frequency signal from the myocardial walls were normalized for those from the pericardial interface and were expressed as percentages (integrated backscatter index). RESULTS: In comparison with baseline, the treated hypertensives showed significant decreases in mean blood pressure, left ventricular mass index, and septal and posterior wall thickness. However, integrated backscatter index values were similar at baseline and after therapy for both the septum and the posterior wall. CONCLUSION: Antihypertensive therapy with enalapril does not increase myocardial reflectivity, although it does induce regression of left ventricular hypertrophy. This suggests that, in accord with experimental data, regression of hypertrophy is achieved by enalapril through a proportionate regression of the myocyte and connective tissue components of the myocardium.

In vivo radiofrequency-based ultrasonic tissue characterization of the atherosclerotic plaque.

BACKGROUND AND PURPOSE: The ultrasonic image can offer unique information on the composition of atherosclerotic plaque, ie, the relative content of lipids, fibrous tissue, and calcific deposits. To date, however, the echographic assessment of plaque structure is based on a subjective, qualitative evaluation of the bidimensional images. We evaluated the feasibility and accuracy of assessing, in vivo, the acoustic properties of arterial carotid plaques by means of a suitably modified echographic apparatus allowing direct access to the radiofrequency signal. METHODS: In 15 patients undergoing carotid thromboendarterectomy, the ultrasonic findings in 70 discrete sites (within the plaque, n = 54; normal sites, n = 11; or intraluminal thrombi, n = 5) were correlated with the histological analysis (hematoxylin-eosin and Mallory trichrome stains) independently performed on the arterial samples. The pathological examination was carried out at a similar level of the insonation; the sites analyzed within the plaque were chosen because of their uniform echoic characteristics. In each ultrasonic region of interest selected from the echographic image, the integrated amplitude of the rectified radiofrequency signal was measured as the integrated backscatter index. RESULTS: The intimal-medial layer of normal carotid wall (n = 11) exhibited values of -32.5 +/- 9.4 dB. The integrated backscatter index in fatty sites (n = 11, -40.3 +/- 5.4 dB) differed from that of fibrous (n = 12, -23.8 +/- 5.0 dB) and calcified (n = 26, -11.5 +/- 5.2 dB, P < .01 for all intergroup differences) sites. Intraluminal thrombotic sites (n = 5, -42 +/- 5.1 dB, P < .01) differed from fibrous and calcified subsets (P < .01) but overlapped (P = NS) with fatty sites. Histological sampling also showed two sites of intraplaque hemorrhage that exhibited very low backscatter values (-53 and -58 dB) and three fibrofatty sites showing backscatter values (-28, -28, and -32 dB) intermediate between the fibrous and the fatty subsets. CONCLUSIONS: Quantitative analysis of integrated backscatter of the arterial wall is feasible in humans and provides an operator-independent assessment of plaque echoic structure. In particular, integrated backscatter is effective in distinguishing lipidic, fibrotic, and calcific components in human atherosclerotic plaques.

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)

Flow quantitation by radio frequency analysis of contrast echocardiography.

Contrast echocardiography has the potential for measuring cardiac output and regional blood flow. However, accurate quantitation is limited both by the use of non-standard contrast agents and by the electronic signal distortion inherent to the echocardiographic instruments. Thus, the aim of this study is to quantify flow by combining a stable contrast agent and a modified echo equipment, able to sample the radio frequency (RF) signal from a region of interest (ROI) in the echo image. The contrast agent SHU-454 (0.8 ml) was bolus injected into an in vitro calf vein, at 23 flow rates (ranging from 376 to 3620 ml/min) but constant volume and pressure. The ROI was placed in the centre of the vein, the RF signal was processed in real time and transferred to a personal computer to generate time-intensity curves. In the absence of recirculation, contrast washout slope and mean transit time (MTT) of curves (1.11-8.52 seconds) yielded excellent correlations with flow: r = 0.93 and 0.95, respectively. To compare the accuracy of RF analysis with that of conventional image processing as to flow quantitation, conventional images were collected in the same flow model by two different scanners: a) the mechanical sector scanner used for RF analysis, and b) a conventional electronic sector scanner. These images were digitized off-line, mean videodensity inside an identical ROI was measured and time-intensity curves were built. MTT by RF was shorter than by videodensitometric analysis of the images generated by the same scanner (p < 0.001). In contrast, MTT by RF was longer than by the conventional scanner (p < 0.001). Significant differences in MTT were also found with changes in the gain setting controls of the conventional scanner. To study the stability of the contrast effect, 6 contrast injections (20 ml) were performed at a constant flow rate during recirculation: the spontaneous decay in RF signal intensity (t1/2 = 64 +/- 8 seconds) was too long to affect MTT significantly. In conclusion, the combination of a stable contrast agent and a modified echocardiographic instrument provides accurate quantitation of flow in an in vitro model; RF analysis is more accurate than conventional processing as to flow quantitation by contrast echocardiography.

Normal ultrasonic myocardial reflectivity in hypertensive patients. A tissue characterization study.

Ultrasonic backscatter of myocardial walls is directly related to the morphometrically evaluated collagen content in humans. The integrated backscatter is also increased in hypertrophic cardiomyopathy, whereas it gives normal values in the physiological hypertrophy of elite athletes. We assessed the quantitatively evaluated myocardial reflectivity in 46 mild to moderate, clinically uncomplicated essential hypertensive patients, with echocardiographically assessed normal regional and global left ventricular function, and 22 age- and sex-matched normotensive control subjects. With an echo prototype implemented in our institute, we performed an on-line radiofrequency analysis to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior wall. The integrated values of the radiofrequency signal of myocardial walls were normalized for those of the pericardial interface and expressed as a percent (integrated backscatter index). Hypertensive patients and control subjects differed in mean blood pressure (119 +/- 11 versus 95 +/- 5 mm Hg, p < 0.001) and left ventricular mass index (134 +/- 31 versus 105 +/- 21 g/m2, p < 0.001). However, integrated backscatter index overlapped for both the septum (28 +/- 17% versus 25 +/- 6%, p = NS) and the posterior wall (13 +/- 7% versus 13 +/- 4%, p = NS). In the hypertensive group, there was no detectable correlation between septal integrated backscatter index and either septal thickness (r = -0.26, p = NS) or mean arterial pressure (r = -0.14, p = NS). Hypertensive patients showed a normal pattern of quantitatively assessed ultrasonic backscatter, even in the presence of left ventricular hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative ultrasonic analysis of myocardium in patients with thalassemia major and iron overload.

BACKGROUND: Patients with beta-thalassemia major present with severe anemia and need continuous transfusion therapy. The consequent iron overload leads to hemochromatosis. Initial cardiac dysfunction has been documented even in thalassemics without clinical manifestations of heart failure as well as by conventional echocardiographic-Doppler techniques. The purpose of this study was to assess the acoustic quantitative properties of myocardium in patients with iron overload. METHODS AND RESULTS: Thirty-eight patients with beta-thalassemia major, without clinical signs of cardiac failure, and 20 age- and sex-matched young controls were studied by echocardiography. An on-line analysis of the ultrasonic radiofrequency signal was performed to obtain quantitative operator-independent measurements of the integrated backscatter (IB) signal of the ventricular septum and the posterior wall. The integrated values of the radiofrequency signal were normalized for the pericardial interface and expressed in percent (IB%). Thalassemic patients had been receiving transfusion therapy for 16 +/- 5 years and had received 313 +/- 138 transfusion units; they all had received chelation treatment (desferroxiamine) for 9 +/- 2 years. Patients and controls showed comparable values of echocardiographically assessed percent fractional shortening (32 +/- 3% versus 36 +/- 4%, p = NS), whereas thalassemics showed higher values of left ventricular mass index (118 +/- 30 versus 98 +/- 15 g/m2, p < 0.05). The IB% values were higher in patients with thalassemia major than in controls for both septum (35 +/- 14% versus 21 +/- 6%, p < 0.001) and posterior wall (16 +/- 6% versus 11 +/- 3%, p < 0.001). In thalassemic patients, no significant correlation was found between the septum IB% value and hematological parameters, such as the total number of transfusions (r = 0.2, p = NS) or the mean ferritin value (r = 0.1, p = NS). No significant correlation was also found between the septum IB% value and the echocardiographically assessed left ventricular mass index (r = 0.2, p = NS). CONCLUSIONS: These data demonstrate that myocardial reflectivity is abnormally increased in patients with thalassemia major under transfusion treatment, probably due to myocardial iron deposits and/or secondary structural changes. These quantitatively assessed abnormalities in regional reflectivity can be detected when conventional echocardiographic parameters of systolic left ventricular function are undistinguishable from normal controls.

Quantitative assessment of ultrasonic myocardial reflectivity in hypertrophic cardiomyopathy.

The purpose of this study was to investigate the relation between acoustic properties of the myocardium and magnitude of left ventricular hypertrophy in patients with hypertrophic cardiomyopathy. An on-line radio frequency analysis system was used to obtain quantitative operator-independent measurements of the integrated backscatter signal of the ventricular septum and posterior free wall in 25 patients with hypertrophic cardiomyopathy and 25 normal age-matched control subjects. The integrated values of the radio frequency signal were normalized for the pericardial interface and expressed in percent. Tissue reflectivity was significantly increased in the hypertrophied ventricular septum, as well as in the nonhypertrophied posterior free wall, in patients with hypertrophic cardiomyopathy (58 +/- 15% and 37 +/- 12%, respectively) compared with values in normal subjects (33 +/- 10% and 18 +/- 5%, respectively; p less than 0.001). Furthermore, measurements of reflectivity of the septum or posterior free wall, or both, were beyond 2 SD of normal values in greater than 90% of the patients and were also abnormal in each of the five study patients who had only mild and localized left ventricular hypertrophy. No correlation was identified between myocardial tissue reflectivity and left ventricular wall thickness in the patients with hypertrophic cardiomyopathy (correlation coefficient r = 0.4; p = NS). These findings demonstrate that myocardial reflectivity is abnormal in most patients with hypertrophic cardiomyopathy and is largely independent of the magnitude of left ventricular hypertrophy. Moreover, quantitative analysis of ultrasonic reflectivity can differentiate patients with hypertrophic cardiomyopathy from normal subjects independently of clinical features and conventional echocardiographic measurements.

In vivo identification of mitral valve fibrosis and calcium by real-time quantitative ultrasonic analysis.

Conventional echocardiography provides fundamental information about mitral valve morphology and function but has a relatively low specificity in evaluating valve calcific deposits, which is critical information for the preoperative decision to perform commisurotomy or replacement. In vitro radiofrequency ultrasonic quantitative analysis of the mitral valve has been demonstrated to be a reliable tool in identifying normal, fibrotic and calcific valves. This study evaluates quantitative ultrasound characterization of the mitral valve in vivo. Thirty-three patients, scheduled to undergo mitral valve replacement, and 20 normal subjects (10 young and 10 older control subjects) were studied with a 2.25-MHz transducer. Radiofrequency signal was analyzed by a microprocessor system (used with an M-mode commercially available echocardiograph) for on-line evaluation of ultrasonic backscatter with 8 bits of amplitude resolution, 40-MHz sampling rate and a 1-microsecond acquisition gate. The integrated value of the rectified radiofrequency signal amplitude was deemed the integrated backscatter index. The highest value recorded with the ultrasonic analysis from each valve was taken as representative and expressed as the percent value with respect to the pericardial integrated backscatter index value of that subject. The 33 excised mitral valves underwent histologic examination. Four groups were identified: young controls (group I, n = 10); older controls age-matched with patients (group II, n = 10); patients with fibrotic mitral valves (group III, n = 13); and patients with calcific mitral valves (group IV, n = 20).(ABSTRACT TRUNCATED AT 250 WORDS)

In vitro identification of different degrees of mitral valve disease by online evaluation of radiofrequency ultrasound signal.

Sixty five mitral valves were studied in vitro with a 2.25 MHz transducer. Radiofrequency signals were analysed by a microprocessor system (implemented on an M-mode commercially available echocardiography) for online evaluation of ultrasonic backscatter (8 bits of amplitude resolution, 40 MHz sampling rate, 1 microsecond acquisition gate). The integrated value of the rectified signal amplitude was expressed as the integrated backscatter index (in db). The highest value recorded with ultrasonic scanning of each sample was taken as representative of that specimen. Calcification of mitral valves was assessed by radiography (24 mitral valves). Non-calcified mitral calves underwent pathological examination, and fibrotic valves (22 mitral valves) were differentiated from normal valves (19 mitral valves). A statistically significant (p less than 0.005) difference was recorded among the three groups for the index maximal value: calcific -7.4(3.1) db (mean(SD)), fibrotic -18.9(4.9) db, and normal -37.9(7.6) db. In conclusion, a microprocessor based system for online evaluation of radiofrequency ultrasonic signals, which may also be feasible for in vivo studies, provided a clear differentiation in vitro of calcific, fibrotic, and normal mitral valves.

On-line two-dimensional evaluation of ultrasonic integrated backscatter.

We describe an apparatus for the on-line evaluation of integrated backscatter from areas of tissue. The equipment is fully integrated into a B-mode ultrasonic system; there are therefore no new operating procedures to be learned. It provides a simultaneous display of conventional information, together with parameters of tissue characterization. The apparatus is fast and, over a broad diagnostic frequency range, may be used in conjunction with conventional equipment employing transducers.

In vivo radiofrequency ultrasound analysis of normal human heart structures.

Twenty young subjects were studied with a microprocessor system for quantitative analysis of backscattered radiofrequency (RF) signals from normal heart structures. This system allows an "on line" quantitative evaluation of the amplitude of the RF "native" signal, before the chain of processing and display, with the acquisition gate displayed on a conventional M-mode machine. Septum, posterior wall, and anterior mitral leaflet were analyzed. The gate length was kept at 3 microseconds (2.35 mm) for the ventricular walls (excluding endo- and epicardial reflections), and at 1 microsecond (0.8 mm) for the mitral valve. Integrated backscatter index (IBI) was calculated as the time integral of [u(t)[, where u(t) = i(t) X s(t); is the time sequence of backscattered echoes and s(t) is the time gate delimiting the thickness of the insonated tissue. The IBI was expressed in percent, normalized for the pericardial interface (the strongest reflection was assumed to be 100%). The percent IBI for the septum was found to be 22 +/- 4%; for the posterior wall it was 17 +/- 3%; for the anterior mitral leaflet it was 5 +/- 2%. A second reading of the same structures was performed by the previous observer and by a new one. Good intraobserver (r = 0.92) and interobserver (r = 0.88) correlations were obtained. In conclusion, a regional variation in echo amplitude from different heart structures can be observed in man. This set of values can be used as normal values for future studies in pathologic conditions.

The use of frequency histograms of ultrasonic backscatter amplitudes for detection of atherosclerosis in vitro.

This study was designed to determine whether a quantitative analysis of integrated backscatter amplitude distribution is potentially useful in characterizing the atherosclerotic lesion. One hundred measurements (10 X 10 array) were made in fresh aortic regions (2 cm X 2 cm) of nine normal and 19 atherosclerotic arterial walls. A 10 MHz transducer was used. The integrated backscatter distinguished normal from atherosclerotic specimens (-56.7 +/- 4.3 vs -42.5 +/- 8.9 dB, p less than .01). The shape of the integrated backscatter amplitude distribution was analyzed by calculation of skewness and kurtosis of each arterial region. Both skewness values (0.134 +/- 0.325 vs -0.193 +/- 0.491 in normal and atherosclerotic segments, respectively, p = NS) and kurtosis values (0.055 +/- 0.765 vs -0.610 +/- 0.379, p less than .01) discriminated between the two groups. When only the six atherosclerotic specimens with mostly fatty and fibrofatty sites were considered, skewness and kurtosis still distinguished normal from atherosclerotic regions (0.134 +/- 0.325 vs -0.404 +/- 0.232, p less than .05 and 0.055 +/- 0.765 vs -0.558 +/- 0.337, p less than .05, respectively), while integrated backscatter values did not (-56.7 +/- 4.5 vs -52.3 +/- 6.1 dB, p = NS). In conclusion, atherosclerosis may be detected in vitro by the quantitative analysis of integrated backscatter distribution. This variable could also be of help in the identification of less obvious forms of atherosclerotic disease that are not distinguishable on the basis of integrated backscatter amplitude.

On-line evaluation of ultrasonic integrated backscatter.

Although it is already known that reflected ultrasonic signals (backscatter) are changed by the structure of the tissue through which they pass, clinicians are still awaiting a practical instrument in which information from backscatter reflections will serve as a diagnostic aid additional to that provided by conventional ultrasonic scans. The equipment described here is both small and fast, and is integrated into a normal ultrasound installation. No new operating procedures have to be learned. The integrated backscatter is calculated on-line and presented on an LED as tissue characterization parameters. In order to minimize noise due to physical movement of the heart during an investigation of the myocardium, the analysis is synchronized with the ECG; and as an aid to the user, the normal system VDU displays both the ECG and the activating trigger pulse derived from the R-wave peak. An A-scan display has been used but this could readily be adapted for B-scan operation and single line analysis. Tests with backscattering models and standard instrumentation have shown no significant difference between results using time domain or frequency domain analysis.

[Joint pain crises and chronic inflammatory-reactive phenomena: a unitary approach with proglumetacin]. / Crisi algiche articolari e fenomeni flogistico-reattivi cronici: un approccio unitario con la proglumetacina.

Nineteen patients with acute joint pain and 12 patients with chronic rheumatic disorders were treated with 450 mg/day of proglumetacin for a period ranging between 15 and 30 days. The overall results revealed a satisfactory response to treatment, and tolerance was rated as "good" or "very good" in all patients.