Experimental validation of nonsteady rate measurements using a tracer infusion method and inulin as tracer and tracee.
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Results for “Experimental validation”
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CT assessment of cerebral perfusion: experimental validation and initial clinical experience.
PURPOSE: To validate a dynamic single-section computed tomographic (CT) method to measure cerebral blood volume (CBV) and cerebral blood flow (CBF) by using a noncarotid artery as the input and to demonstrate the feasibility of this method in a pilot series of patients. MATERIALS AND METHODS: Twelve dynamic contrast material-enhanced CT studies were performed in beagles. CBV, CBF, and mean transit time (MTT) values were calculated by using an internal carotid artery (ICA) and a noncarotid artery as the input artery to the brain. Patient studies with use of the radial artery as the input were performed (a) repetitively in two patients after subarachnoid hemorrhage, (b) in a patient with a symptomatic ICA occlusion before and after the intravenous injection of 1 g of acetazolamide, and (c) in a patient with a malignant brain tumor. RESULTS: Linear regression analyses revealed highly significant correlations (P < .001) between CBV (r, 0.98; slope, 0.96), CBF (r, 0.89; slope, 0.87), and MTT (r, 0.80; slope, 0.76) values calculated with the ICA and the noncarotid inputs. The CT-derived patient data correlated well with ancillary clinical and neuroradiologic findings. CONCLUSION: Dynamic single-section CT scanning to measure CBV and CBF on the basis of a noncarotid input is a highly accessible and cost-effective blood flow measurement technique.
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Experimental validation of measurements of glucose turnover in nonsteady state.
The aim of the present experiments is to validate, in conscious dogs, the tracer infusion methods of measuring nonsteady turnover rates. This was done in nine experiments performed in four normal dogs by infusing isotopically labeled glucose (2-3H, 6-3H, 1-14C) and monitoring the concentrations of both the labeled and unlabeled substances. The validation is based on the observation that a high exogenous infusion of glucose will suppress endogenous glucose production and become the sole source of glucose in the body. By infusing glucose at a high, time-varying rate, calculating its rate of appearance, (Ra) and comparing it to the infused rate, the method can be verified. The calculations were based on: a) a single-compartment model with a modified volume of distribution; b) a two-compartment model; and c) a generalized dispersion model. The absolute values of the areas of the deviations of the calculated from the infused curves were found to be, respectively, 9.5, 8.4, and 7.8 percent of the total area under the infused curve. It was concluded that the tracer infusion method can reliably measure Ra of glucose when it is changing rapidly, and the system is out of steady state.
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Impulse-response function of splanchnic circulation with model-independent constraints: theory and experimental validation.
Modeling physiological processes using tracer kinetic methods requires knowledge of the time course of the tracer concentration in blood supplying the organ. For liver studies, however, inaccessibility of the portal vein makes direct measurement of the hepatic dual-input function impossible in humans. We want to develop a method to predict the portal venous time-activity curve from measurements of an arterial time-activity curve. An impulse-response function based on a continuous distribution of washout constants is developed and validated for the gut. Experiments with simultaneous blood sampling in aorta and portal vein were made in 13 anesthetized pigs following inhalation of intravascular [15O]CO or injections of diffusible 3-O-[11C]methylglucose (MG). The parameters of the impulse-response function have a physiological interpretation in terms of the distribution of washout constants and are mathematically equivalent to the mean transit time (T) and standard deviation of transit times. The results include estimates of mean transit times from the aorta to the portal vein in pigs: T = 0.35 +/- 0.05 min for CO and 1.7 +/- 0.1 min for MG. The prediction of the portal venous time-activity curve benefits from constraining the regression fits by parameters estimated independently. This is strong evidence for the physiological relevance of the impulse-response function, which includes asymptotically, and thereby justifies kinetically, a useful and simple power law. Similarity between our parameter estimates in pigs and parameter estimates in normal humans suggests that the proposed model can be adapted for use in humans.
3-O-Methylglucose↗
Aortic pressure-diameter relationship assessed by intravascular ultrasound: experimental validation in dogs.
Intravascular ultrasound (IVUS) has emerged as an important diagnostic method for evaluating vessel diameter and vessel wall motion. To evaluate the validity of IVUS in assessing changes in the pressure-diameter relationship we compared measurements of abdominal aortic diameters derived from IVUS with those simultaneously obtained at the same site using implanted sonomicrometers in five chronically instrumented conscious dogs and in seven acutely instrumented anesthetized dogs. Five hundred eighty beats were analyzed to obtain peak systolic and end-diastolic diameters and to calculate aortic compliance at different blood pressure levels induced either by an aortic pneumatic cuff or by intravenous injections of nitroglycerin or norepinephrine. IVUS agreed closely with sonomicrometer measurements at different blood pressure levels. However, IVUS slightly but significantly underestimated aortic diameters by 0.6 +/- 0.7 mm for systolic diameters (P < 0.001) and by 0.7 +/- 0.6 mm for diastolic diameters (P < 0.001) compared with the sonomicrometer measurements. We conclude that IVUS is a feasible and reliable method to measure dynamic changes in aortic dimensions and has the potential to provide ready access to assess aortic compliance in humans.
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Definition of arterial compliance. Re: Hardt et al., "Aortic pressure-diameter relationship assessed by intravascular ultrasound: experimental validation in dogs.".
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Experimental validation of the countercurrent model of urinary concentration.
This essay looks at the historical significance of four APS classic papers that are freely available online: Jolliffe N, Shannon JA, and Smith HW. The excretion of urine in the dog. III. The use of non-metabolized sugars in the measurement of the glomerular filtrate. Am J Physiol 100: 301-312, 1932 (http://ajplegacy.physiology.org/cgi/reprint/100/2/301). Shannon JA. The excretion of inulin by the dog. Am J Physiol 112: 405-413, 1935 (http://ajplegacy.physiology.org/cgi/reprint/112/3/405). Shannon JA and Fisher S. The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122: 765-774, 1938 (http://ajplegacy.physiology.org/cgi/reprint/122/3/765). Shannon JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J Physiol 133: 752-761, 1941 (http://ajplegacy.physiology.org/cgi/reprint/133/3/752).
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Microvascular resistance is not influenced by epicardial coronary artery stenosis severity: experimental validation.
BACKGROUND: The effect of epicardial artery stenosis on myocardial microvascular resistance remains controversial. Recruitable collateral flow, which may affect resistance, was not incorporated into previous measurements. METHODS AND RESULTS: In an open-chest pig model, distal coronary pressure was measured with a pressure wire, and the apparent minimal microvascular resistance was calculated during peak hyperemia as pressure divided by flow, measured either with a flow probe around the coronary artery (R(micro app)) or with a novel thermodilution technique (apparent index of microcirculatory resistance [IMR(app)]). These apparent resistances were compared with the actual R(micro) and IMR after the coronary wedge pressure and collateral flow were incorporated into the calculation. Measurements were made at baseline (no stenosis) and after creation of moderate and severe epicardial artery stenoses. In 6 pigs, 189 measurements of R(micro) and IMR were made under the various epicardial artery conditions. Without consideration of collateral flow, R(micro app) (0.43+/-0.12 to 0.46+/-0.10 to 0.51+/-0.11 mm Hg/mL per minute) and IMR(app) (14+/-4 to 17+/-7 to 20+/-10 U) increased progressively and significantly with increasing epicardial artery stenosis (P<0.001 for both). With the incorporation of collateral flow, neither R(micro) nor IMR increased as a result of increasing epicardial artery stenosis. CONCLUSIONS: After collateral flow is taken into account, the minimum achievable microvascular resistance is not affected by increasing epicardial artery stenosis.
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Spectral analysis of arterial bruits (phonoangiography): experimental validation.
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Experimental validation of quantitative coronary arteriography for determining pressure-flow characteristics of coronary stenosis.
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Animals↗
Intraoperative evaluation of coronary artery bypass graft anastomoses with high-frequency epicardial echocardiography: experimental validation and initial patient studies.
There is currently no accepted approach for intraoperative evaluation of the technical adequacy of coronary artery bypass graft anastomoses. High-frequency epicardial echocardiography performed intraoperatively could assess coronary artery bypass graft anastomoses by providing on-line short-axis (cross-sectional) and longitudinal two-dimensional images of the vessels. To validate measurements of anastomoses with high-frequency epicardial echocardiography, luminal diameter determined by high-frequency epicardial echocardiography was compared with that determined histologically after perfusion fixation in 12 dogs studied after coronary artery bypass grafting. Technical errors were deliberately created in some grafts. The results of these animal validation studies showed that maximum luminal diameter of the anastomosis by high-frequency epicardial echocardiography correlated well with histologic measurements (r = .92; high-frequency epicardial echocardiography = 0.8 histology + 0.3). All deliberately created technical errors were detected by an independent observer using high-frequency epicardial echocardiography. After completion of the animal studies, we demonstrated the clinical applicability of this approach in 12 patients. Fifteen coronary artery bypass graft anastomoses were examined intraoperatively with high-frequency epicardial echocardiography. The measured maximum luminal diameter of the anastomosis was greater than the maximum luminal diameter of the native artery, as expected, in all end-to-side anastomoses. However, the maximum luminal diameter of the side-to-side anastomoses was equal to or slightly less than that of the native artery. In this initial patient group, minor technical errors were noted in two of 15 graft anastomoses. In conclusion, high-frequency epicardial echocardiography can accurately measure coronary arterial bypass graft anastomoses and has potential for intraoperative detection of technical errors and inadequacies.
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Quantitation of absolute area of a coronary arterial stenosis: experimental validation with a preparation in vivo.
The absolute cross-sectional area of a coronary stenosis measured by quantitative coronary angiography correlates well with its hemodynamic significance. We evaluated a combined approach using edge detection applied to the normal segment and videodensitometry applied to the stenosis to determine the absolute cross-sectional area of the stenosis (videodensity method). The results were then compared with those with the edge detection method applied directly to the stenosis. The area of the stenosis by the edge detection method was calculated by analyzing two orthogonal projections for irregular stenoses and with use of the formula for the area of an ellipse (ellipse method). The accuracy of both these techniques was assessed by analyzing digital angiograms acquired from closed-chest dogs in which 10 plastic cylinders with precisely machined circular and irregular lumina were inserted into the coronary arteries. Angiograms of irregular stenoses were acquired in two orthogonal views. The ellipse method applied to circular stenoses was very accurate, with r = .97, average absolute difference (AAD) = 0.21 mm2, and SEE = 0.30. For the videodensity method r = .97, AAD = 0.84 mm2, and SEE = 0.40. Irregular stenoses were better quantitated by the videodensity method applied in one view (AAD = 0.50 mm2, SEE = 0.47) than by the ellipse method applied in two orthogonal projections (AAD = 1.03 mm2, SEE = 0.87). Overall, the two methods were comparable in accuracy (for videodensity, AAD = 0.65 mm2, SEE = 0.71 vs AAD = 0.54 mm2, SEE = 0.79 for ellipse).(ABSTRACT TRUNCATED AT 250 WORDS)
Angiography↗
Experimental validation of Doppler echocardiographic measurement of volume flow through the stenotic aortic valve.
In aortic stenosis, evaluation of aortic valve area by the continuity equation assumes that the volume of flow through the stenotic valve can be measured accurately in the left ventricular outflow tract. To test the accuracy of Doppler volume-flow measurement proximal to a stenotic valve, we developed an open-chest canine model in which the native leaflets were sutured together to create variable degrees of acute aortic stenosis. Left ventricular and aortic pressures were measured with micromanometer-tipped catheters. Volume flow was controlled and varied by directing systemic venous return through a calibrated roller pump and back to the right atrium. Because transaortic volume flow will not equal roller pump output when there is coexisting aortic insufficiency (present in 67% of studies), transaortic flow was measured by electromagnetic flowmeter with the flow probe placed around the proximal descending thoracic aorta, just beyond the ligated arch vessels. In 12 adult, mongrel dogs (mean weight, 25 kg), the mean transaortic pressure gradient ranged from 2 to 74 mm Hg, and transaortic volume flow ranged from 0.9 to 3.2 l/min. In four dogs, electromagnetic flow that was measured distal to the valve was accurate compared with volume flow determined by timed collection of total aortic flow into a graduated cylinder (n = 24, r = 0.97, electromagnetic flow = 0.87 Direct +0.13 l/min). In eight subsequent dogs, electromagnetic flow was compared with transaortic cardiac output measured by Doppler echocardiography in the left ventricular outflow tract as circular cross-sectional area [pi(D/2)2] x left ventricular outflow tract velocity-time integral x heart rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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A mathematical model for the quantification of mitral regurgitation. Experimental validation in the canine model using contrast echocardiography.
BACKGROUND: Because the clearance of contrast from the left atrium (LA) relative to the left ventricle (LV) depends on the degree of mitral regurgitation (MR), we hypothesized that a mathematical model can be developed that would provide a quantitative estimation of MR from the washout of contrast from these chambers. METHODS AND RESULTS: After mathematically developing the model, we performed experiments in two groups of dogs with the use of contrast echocardiography. Group 1 consisted of nine dogs in which different degrees of MR were produced by creating ischemic LV dysfunction. Contrast was injected into the LV, and MR was graded visually on a scale of from 0 to 4+. Videointensity plots generated from the LA and LV were provided to the model. There was excellent correlation between visual assessment of MR and model-derived regurgitant fraction in the 33 stages: y = 0.16x + 0.002 (r = 0.97, p less than 0.001, SEE = 0.06). To obtain a more quantitative validation, we placed electromagnetic flow probes on the aorta and just cephalad to the mitral annulus in six dogs (group 2) during cardiopulmonary bypass. Different degrees of MR were produced by chordal traction and/or myocardial ischemia. Regurgitant fraction was calculated at each stage from the flow probe and videointensity data. There was excellent correlation between flow probe and model-derived regurgitant fraction (y = 0.90x + 0.03; r = 0.96, p less than 0.001, SEE = 0.06), and close interobserver and intraobserver correlations were noted using flow probe and contrast echocardiographic data. CONCLUSIONS: A mathematical model that uses the clearance of contrast from the LA relative to the LV can be used to accurately measure the severity of MR. These findings may have important practical implications for the quantification of MR.
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Papillary muscle displacement causes systolic anterior motion of the mitral valve. Experimental validation and insights into the mechanism of subaortic obstruction.
BACKGROUND: Systolic anterior motion (SAM) of the mitral valve in hypertrophic cardiomyopathy (HCM) has generally been explained by a Venturi effect related to septal hypertrophy, causing outflow tract narrowing and high velocities. Patients with HCM, however, also have primary abnormalities of the mitral apparatus, including anterior and inward or central displacement of the papillary muscles, and leaflet elongation. These findings have led to the hypothesis that changes in the mitral apparatus can be a primary cause of SAM by altering the forces acting on the mitral valve and its ability to move in response to them. Despite suggestive observations, however, it has never been prospectively demonstrated that such changes can actually cause SAM. METHODS AND RESULTS: To test this hypothesis in vivo, anterior papillary muscle displacement was created in 7 dogs studied by echocardiography, with controlled cardiac output and heart rate. In all 7 dogs, papillary muscle displacement caused SAM, with an outflow tract gradient (33 +/- 19 mm Hg) and mitral regurgitation in 6. As in patients with HCM, the mitral valve was displaced anteriorly and the coaptation point shifted toward the insertion of the leaflets, creating longer distal residual leaflets that moved anteriorly. CONCLUSIONS: Primary changes in the mitral apparatus can cause SAM without septal hypertrophy. In this model, SAM appears to be determined by the ability of the leaflets to move anteriorly (papillary muscle displacement causing slack and increased residual leaflet length) and their interposition into the outflow stream by anterior displacement, determining the direction of this motion. Geometric factors observed in HCM and in patients with SAM without HCM can therefore play a primary role in causing SAM.
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Noninvasive quantification of regional myocardial metabolic rate of oxygen by 15O2 inhalation and positron emission tomography. Experimental validation.
BACKGROUND: The purpose of this study was to validate a novel method for noninvasive quantification of regional myocardial oxygen consumption (MMRO2, mL.min-1 x 100 g-1) and oxygen extraction fraction (OEF) by use of positron emission tomography (PET) and inhalation of 15O-labeled molecular oxygen gas (15O2). METHODS AND RESULTS: Twenty-four measurements were performed in eight closed-chest anesthetized greyhounds at baseline and during infusions of adenosine (100 to 200 micrograms.kg-1.min-1), isoproterenol (1 to 10 microgram/min), and propranolol (5 mg botus +0.2 to 1 mg/min) with morphine (5 mg slow infusion +0.2 to 0.5 mg/ min) to obtain a wide range of oxidative metabolism. The PET imaging protocol consisted of 15O2 emission (OEF and MMRO2), transmission, [15O]CO emission (blood pool), and [15O]CO2 emission (myocardial blood flow: MBF(pets) mL.min-1.g-1) scans. OEF was calculated from the PET data (OEFpet) by three different analytical techniques: steady-state, 5-minute, and 8-minute autoradiographic analyses. Reference measurements of MBF (MBFref) and OEF (OEFref) were obtained during 15O2 inhalation with radiolabeled microspheres and paired arterial and coronary sinus blood sampling, respectively. MMRO2 was calculated from the PET (MMRO2pet) and the reference (MMRO2ref) data as follows: MMRO2 = OEF x MBF x (O2 content of arterial blood). OEF measured by the steady-state PET method was well correlated with the reference data over the range 0.16 to 0.73 (OEFpet = 1.03 OEFref -0.01, r = .97), as was MMRO2 over the range 2.4 to 27.5 mL.min-1 x 100 g-1 (MMRO2pet = 0.98 MMRO2ref +0.91, r = .94). OEFpet calculated by use of the 5-minute and 8-minute autoradiographic analyses were equally well correlated with the reference measurements (r = .95 and r = .97, respectively). There were no significant differences between values of MMRO2pet calculated by use of the steady-state, 5-minute, and 8-minute autoradiographic analyses (P = NS by ANOVA). Regional values of MBFpet, OEFpet, and MMRO2pet were homogeneously distributed and similar to the whole-heart values both at baseline and during the various pharmacological interventions. CONCLUSIONS: Accurate quantification of OEF and MMRO2 is feasible with 15O2 inhalation and PET imaging using both the steady-state and autoradiographic analytical approaches. These studies suggest the applicability of this method for quantitative assessments of regional cardiac oxidative metabolism in clinical studies.
Adenosine↗
Measurement of regional cerebral blood flow in the dog using ultrafast computed tomography. Experimental validation.
The applicability, feasibility, reproducibility, and accuracy of the method of measuring regional cerebral blood flow using ultrafast computed tomography were evaluated in 25 dogs under varying physiological and pathophysiological conditions. Regional cerebral blood flow values were 75.6 +/- 29.4 ml/100 g/min (mean +/- standard deviation) for the hemisphere, 68.4 +/- 28.2 ml/100 g/min for the basal ganglia, 41.2 +/- 15.0 ml/100 g/min for the internal capsule, and 80.8 +/- 37.2 ml/100 g/min for the neocortex. Measurements made 10 minutes apart were significantly (p less than 0.05) correlated. Simultaneous measurements of regional cerebral blood flow by the microsphere and ultrafast computed tomography methods showed a significant (p less than 0.05) correlation for the hemisphere (r = 0.95), basal ganglia (r = 0.95), and neocortex (r = 0.94) but not for the internal capsule (r = 0.51). Microsphere and ultrafast computed tomography regional cerebral blood flow values were also in agreement in radiation-damaged brain with appreciable blood-brain barrier breakdown, and the two methods demonstrated similar responsiveness of regional cerebral blood flow to alterations in arterial carbon dioxide tension. The accuracy and sensitivity of the ultrafast computed tomography technique suggests that it affords a useful new tool for studying normal and abnormal regional cerebral blood flow.
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Coronary thermodilution to assess flow reserve: experimental validation.
BACKGROUND: Fractional flow reserve (FFR) and coronary flow reserve (CFR) are indices of coronary stenosis severity that provide the clinician with complementary information on the contribution of epicardial arteries and microcirculation to total resistance to myocardial blood flow. At present, FFR and CFR can only be obtained by 2 separate guidewires. The present study tested the validity of the thermodilution principle in assessing CFR with one pressure-temperature sensor-tipped guidewire. METHODS AND RESULTS: In an in vitro model, absolute flow was compared with the inverse mean transit time (1/T(mn)) of a thermodilution curve obtained after a bolus injection of 3 mL of saline at room temperature. A very close correlation (r>0.95) was found between absolute flow and 1/T(mn) when the sensor was placed >/=6 cm from the injection site. In 6 chronically instrumented dogs (60 stenoses; FFR from 0.19 to 0.98), a significant linear relation was found between flow velocity and 1/T(mn). A significant correlation was found between CFR(Doppler), which was calculated from the ratio of hyperemic to resting flow velocities, and CFR(thermo), which was calculated from the ratio of resting to hyperemic T(mn) (r=0.76; SEE=0.24; P<0.001). CONCLUSION: The present findings demonstrate the validity of the thermodilution principle to assess CFR. Because the pressure-temperature sensor was mounted in a commercially available angioplasty guidewire, this technique permits simultaneous measurements of CFR and FFR.
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