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Biomedical subjects

W H Knapp

Publications and source records attributed to W H Knapp.

At least 19 recordsLinked to original sources

[Results of myocardial scintigraphy in patients with left bundle-branch block using Tl-201 and Tc-99m-MIBI].

Tl-201 myocardial scintigrams in patients with left bundle-branch block (LBBB) are frequently non-diagnostic with respect to presence or absence of coronary artery disease (CAD). The new myocardial perfusion tracer Tc-99m-MIBI requires a different protocol due to its insignificant redistribution. Therefore, scintigraphic patterns in LBBB cannot be deduced from experiences with Tl-201. In a total of 132 patients with LBBB, 81 studies were carried out with Tl-201, another 81 studies with Tc-99m-MIBI. In 30 patients both radiopharmaceuticals were employed. 72% of the Tl-201 scintigraphies in constant LBBB resulted in a reversible septal deficit and 9% in a constant septal deficit. In contrast, 70% of the Tc-99m-MIBI scintigraphies resulted in a constant septal deficit and only 19% in a reversible septal deficit. Similar "discrepancies" were found in LBBB patients in whom CAD has been angiographically excluded (N = 17). All patients, however, with LAD or RCA stenoses and constant LBBB showed reversible septal deficits with either tracer, Tl-201 (N = 12) or Tc-99m-MIBI (N = 10). It is concluded: 1) that the majority of patients with LBBB has reduced septal perfusion, 2) that this reduction is typically stress-independent in absence of CAD, and 3) that this stress-independent perfusion deficit is, in general, only differentiated from stress-induced ischemia (in case of CAD) with using the Tc-99m-MIBI protocol.

Adult

Increased thermal response to ultrasound in the Walker carcinosarcoma treated with vasoactive drugs.

In order to evaluate the potential of a highly selective Ca2+ entry blocker (nisoldipine) and of 5-hydroxytryptamine (5-HT) as adjuvant in hyperthermia treatment, we studied the differential flow response and time-course of tumor and normal tissue temperature following the administration of the two substances and during ultrasound heating. In 12 rats bearing Walker 256 carcinomas i.p. injection of 0.2-0.4 mg/kg nisoldipine caused a reduction in the tumor-to-muscle flow relationship of 4.4 +/- 1.9 (SD) to 1.74 +/- 0.86 as determined by intraarterial 133Xe injection; i.p. injection of 2-8 mg/kg 5-HT (N = 13) caused a respective reduction from 3.9 +/- 2.67 to 1.3 +/- 1.59. During a 20-min period of 41 degrees C normal tissue temperature-controlled ultrasound heating without drugs, tumor temperature attained 40.8 +/- 0.9 degrees C (N = 16). Nisoldipine or 5-HT injection at continuing 41 degrees C normal tissue temperature controlled energy delivery produced an instantaneous further increment of tumor temperature, eventually to 44.0 +/- 1.14 degrees C or 44.2 +/- 1.26 degrees C, respectively, after a period of 20 min. Injection of 0.9% NaCl (N = 4) solution caused only insignificant changes. Blood pressure and muscle perfusion were distinctly influenced by nisoldipine, but not by 5-HT. Since both drugs instantaneously increased the temperature differential between tumor and normal tissue, though by different vasoaction, they should be considered as adjuvants in hyperthermia.

Animals

Regional myocardial nitrogen-13 glutamate uptake in patients with coronary artery disease: inverse post-stress relation to thallium-201 uptake in ischemia.

The purpose of the present study was to evaluate the clinical significance of myocardial scintigraphy with nitrogen-13 (N-13) glutamate as a marker of myocardial metabolism. Within 2 weeks after cardiac catheterization, 25 patients with single vessel left anterior descending coronary artery disease underwent thallium-201 imaging (5 min and 3 h after injection) and N-13 glutamate scintigraphy (10 min after injection). Radionuclide studies were performed in the 30 degrees left anterior oblique projection after symptom-limited bicycle exercise, and regional tracer uptake was quantified by computer-assisted placement of regions of interest within the regions of myocardial activity. Poststenotic tracer uptake in the perfusion bed of the left anterior descending coronary artery (septum) was then normalized to the tracer uptake in the nondiseased left circumflex territory (posterolateral segments = 100%). In 14 patients with a history of previous myocardial infarction (Subgroup A), deficient poststenotic N-13 uptake correlated closely with thallium-201 uptake in both initial (r = 0.82, p less than 0.001) and redistribution (r = 0.74, p less than 0.01) scintigrams. By contrast, in 11 patients with no previous myocardial infarction and normal left ventricular function at rest (Subgroup B), initial uptake of both tracers was inverse: poststenotic N-13 glutamate uptake increased with decreasing thallium-201 uptake during exercise-induced ischemia (r = -0.64, p less than 0.05) and was closely correlated with the percent thallium-201 redistribution (r = 0.74, p less than 0.01). Thus, augmented accumulation of N-13 glutamate in reversibly ischemic (that is, viable) myocardium, and decreased uptake in myocardial scar tissue suggest the clinical usefulness of this metabolic tracer in the differentiation between viable (metabolically active) and irreversibly damaged myocardium.

Coronary Disease

Noninvasive assessment of coronary artery bypass patency: determination of myocardial thallium-201 washout rates.

This prospective study was undertaken to investigate the response of thallium-201 washout rates to coronary artery bypass surgery. Thirty-four patients with coronary heart disease were studied before and after coronary artery bypass grafting, 27 patients with normal coronary arteries serving as controls. All patients underwent cardiac catheterization and thallium-201 serial imaging, including assessment of myocardial washout rates. Pre-operatively, thallium-201 washout rates yielded a considerably higher sensitivity in detection of coronary artery disease, without significant loss of specificity compared to qualitative evaluation of serial static thallium-201 scintigrams. Post-operatively, 50 of 57 segments supplied by a patent graft showed normal washout rates, while in 9 out of 11 segments an occlusion of the graft was indicated by decreased washout rates. Compared to pre- and post-operative qualitative interpretation of static thallium-201 images, the post-operative assessment of washout rates increased both sensitivity (82% vs. 64%) and specificity (88% vs. 77%) for the evaluation of bypass graft patency. Thus, quantitative assessment of thallium-201 washout rates improves the diagnostic reliability of noninvasive detection of myocardial ischaemia with regard to the evaluation of coronary artery bypass graft patency.

Coronary Artery Bypass

Regional myocardial free fatty acid extraction in normal and ischemic myocardium.

The rate constant for free fatty acid influx (k1) was studied in normal and ischemic myocardium. In 15 normal subjects and 30 patients with coronary artery disease, 201Tl and 15-(p-123I-iodophenyl)-pentadecanoic acid (IPPA) were administered during exercise under fasting conditions and at rest. In 10 patients, the study was repeated after percutaneous transluminal coronary angioplasty; in three patients, the study was repeated after infarction. The initial accumulation of IPPA, related to that of 201Tl (both background and crossover corrected), was used for determinations of the regional rate constant of IPPA influx into myocardial tissue (k1*). In normal subjects, no significant differences in k1* between major myocardial segments were found; the average value of k1* was 0.57 +/- 0.13/min (mean +/- SD) at rest and 0.42 +/- 0.06/min at exercise (average workload, 123 +/- 47 W). With increasing free fatty acid plasma concentration and perfusion, free fatty acid influx increased in a saturable fashion. The Michaelis-Menten constant (KM*) and the maximal velocity (Vmax*) for IPPA influx into myocardial tissue were estimated to be 470 nmol/g and 430 nmol/g.min, respectively. In ischemic areas, k1* was reduced to 57 +/- 18% of k1* value in nonaffected segments. The areas were larger than those showing reduced 201Tl uptake. Preinfarction and postinfarction studies showed that the size of 201Tl defects in postinfarction images corresponded with the size of the area with reduced k1* observed in preinfarction scintigrams. Revascularization led to an increase of 201Tl uptake and to normalization of k1*.

Coronary Disease

Effect of methotrexate on perfusion and nitrogen-13 glutamate uptake in the Walker-256 carcinosarcoma.

The tissue uptake of [13N]glutamate (glu) was related to that of [11C]butanol (but), a highly diffusible perfusion tracer. In 25 rats bearing Walker-256 carcinomas tumor-to-muscle glu uptake averaged 6.34 +/- 2.84 (s.d.) prior to interventions and the respective uptake of but was 6.79 +/- 3.08 (y = 0.03 + 0.94x). One hour after selective intraarterial administration of methotrexate (mtx), glu uptake fell by 47%, whereas blood flow remained within the pretreatment range (N = 9). Four hours after mtx, perfusion was reduced by approximately 40%, and 2 days later both perfusion and glu uptake reached extremely low levels. No significant difference in the effect of 10 and 50 mg/kg mtx was observed. Regional tissue mtx uptake estimations using 77Br-labeled bromomethotrexate did not reveal any significant uptake in muscle. The relationship between tumor-to-muscle uptake of glu and but (13N/11C-index) was 0.94 +/- 0.015 (s.e.m., N = 25) before intervention. After methotrexate (1 hr, 4 hr, and 2 days) this index was 0.58 +/- 0.06 (N = 9), and 0.85 +/- 0.04 (N = 11) and 1.03 +/- 0.05 (N = 5), respectively. These values demonstrate an early mtx-induced uncoupling of glu uptake with respect to perfusion.

Animals

Double-nuclide study of the myocardium using 201Tl and 123I-labeled fatty acids in non-ischemic myocardial diseases.

Metabolic impairment and perfusion abnormalities are known to occur in hypertensive heart disease (HHD) and in cardiomyopathies. Free fatty acid (FFA) extraction is severely inhibited in a number of pathobiochemical reactions. This parameter was assessed using the radiolabeled FFA analogue 123I-(p-iodo-phenyl-)-pentadecanoic acid (IPPA) and 201Tl as perfusion marker, both of them injected at maximal physical workload. The regional extraction fraction of IPPA (IPPA-EF) was estimated by relating the regional IPPA and 201Tl uptake to each other. In HHD (normal coronary arteries) with posterior wall thickness less than or equal to 12 mm IPPA-EF was 77 +/- 18% (SD) in septum and 92 +/- 17% in the posterolateral wall (N = 13), with thickness of greater than 12 mm 60 +/- 23% in septum and 61 +/- 20% in the posterolateral wall (N = 8) when compared with IPPA-EF in normal subjects (= 100%, N = 9). In hypertrophic cardiomyopathy (HCM) IPPA-EF averaged 51 +/- 20% in septum and 87 +/- 10% in the posterolateral wall (N = 11). In these patient groups no systematic regional changes in 201TI uptake were observed. In dilated cardiomyopathy (DCM) both IPPA-EF and 201Tl uptake showed distinct regional variations and a great interindividual variability with a mean IPPA-EF reduction of 12% (N = 9). Thus, IPPA uptake in primarily non-ischemic myocardial disease may already be compromised when 201Tl uptake is unchanged. The double-nuclide method for IPPA-EF determination allows to eliminate the influence of flow in FFA imaging and enhances the potential of scintigraphy in the differential diagnosis of HHD versus coronary artery disease.

Cardiomyopathies

Automated determination of the right ventricular ejection fraction by digital processing of 81mKr scintigrams.

A method is presented for the automated determination of the right ventricular ejection fraction (RVEF) by digital image processing of scintigrams obtained by intravenous infusion of Krypton 81m (81mKr) dissolved in a glucose solution. End-diastolic and end-systolic sum pictures were computed by the addition of approximately 30-40 frames selected from the time-activity curve of a preliminary, manually drawn, right ventricular region of interest. After processing these two images with an adaptive Wiener filter, the right ventricular contour was determined by a recently developed algorithm using morphological and functional criteria. The RVEF was calculated for a series of 51 patients from the counts in the detected right ventricular regions in the end-diastolic and end-systolic sum images. In 16 patients without evidence of cardiopulmonary disease, the mean RVEF was 50 +/- 6.1%. RVEF was significantly reduced in 18 patients with obstructive pulmonary disease (42 +/- 6.5%) and in 17 patients with congestive cardiomyopathy (36 +/- 7.1%). The correlation coefficient between two determinations of the RVEF was r = 0.94. Through digital image processing, the determination of the RVEF by radioventriculography with 81m Kr showed high reliability and reproducibility.

Algorithms

Imaging of cerebral blood flow-to-volume distribution using SPECT.

The ratio between cerebral blood flow (CBF) and cerebral blood volume (CBV) has been proposed as an adequate parameter for the evaluation of cerebrovascular disease (CVD), but to date it has not been assessed with SPECT. We have chosen [123I]IMP for CBF and [99mTc] erythrocytes for CBV imaging. The distribution of both nuclides was investigated in succession using corrections for the contamination of the 99mTc tomograms by 123I. The ratio between 123I and 99mTc tomograms yielded the CBF/CBV distribution. Quantitation was obtained by side-to-side comparison of both hemispheres and of segments containing the territories affected by CVD. In 16 patients with CVD, CBF of the affected territories was 85 +/- 19% (s.d.) when related to the nonsymptomatic contralateral side (100%). When the regions of interest defined within one slice encompassed the entire affected hemisphere, the average CBF was 95 +/- 9%, again related to the nonsymptomatic side. The corresponding CBF/CBV data in 15 of these 16 patients were 60 +/- 32% and 81 +/- 16%. In unilateral internal carotid artery stenoses greater than 50% (N = 10), segmental CBF averaged 81.1 +/- 10.1% and CBF/CBV 49.6 +/- 15.5% relative to the contralateral side. The figures for the hemispheres were 92.8 +/- 5.8 and 75.8 +/- 12.6, respectively. These clinical findings mirror the characteristics of CBF autoregulation, namely the vasodilation of small vessels in decreased arterial perfusion pressure. They, therefore, substantiate SPECT imaging of CBF/CBV for the assessment of cerebral perfusion reserve in CVD.

Adult

Nitrogen-13 glutamate uptake and perfusion in Walker 256 carcinosarcoma before and after single-dose irradiation.

Nitrogen-13 (13N) glutamate uptake was recorded in 18 anesthetized rats, both before and at least once after intervention. Each investigation was immediately followed by imaging of blood flow distribution using [11C]butanol. All animals had Walker 256 carcinosarcoma implants in one hind leg. Tumors were locally irradiated with a dose of 800 rad in 14 rats; in four rats, the vasoactive substance 5-hydroxytryptamine (5-HT) was administered. Prior to interventions, the [13N]glutamate tumor-to-muscle uptake showed a linear correlation with blood flow close to identity (y = 0.117 + 0.915x, r = 0.97). After irradiation, a discordant pattern was observed: blood flow tended to increase, while [13N]glutamate tumor-to-muscle uptake dropped from 4.30 +/- 0.66 (s.e.m.) to 3.06 +/- 0.36 (p less than 0.005) during 30 min and attained 4.04 +/- 0.67 2 days later. If [13N]glutamate tumor-to-muscle uptake was related to that of [11C] butanol in each individual animal, this index dropped from 0.93 +/- 0.03 (s.e.m.) to 0.62 +/- 0.04 (p less than 0.001) 30 min after irradiation and attained 0.90 +/- 0.09 after 2 days. In animals treated with 5-HT, [13N]glutamate and [11C]butanol showed a parallel drop from 6.60 +/- 0.84 to 2.10 +/- 0.60 (p less than 0.05) and from 6.8 +/- 0.78 to 2.08 +/- 0.74 (p less than 0.05), respectively. Thus, single-dose irradiation causes [13N]glutamate uptake to be uncoupled with respect to flow, while [13N]glutamate uptake in untreated tumors is flow-limited and responds together with flow on vasomotion.

Animals

Calculation of residence time distributions of intravascular radioactive tracers in fields of external registration.

Because of the physiological significance of the mean velocity of blood flow, indicator dispersion models are of special interest and possess practical relevance, if biological and extraneous variables can be altered. The variables being considered are flow characteristics of the streaming blood, tracer distribution at the entrance into the flow system, and the area in which impulses are collected to form the time-activity curve. Using a simplified version of the general convective diffusion equation (diffusion model) in which the diffusion constant D includes all propagation and mixing of the tracer, a simple numerical method can be applied. The method is used to determine influences of injection and changed regions of interest on the time-activity curve and the following parameters: appearance times, peak times, mean circulation times, and the times of the first inflection points. For this purpose, the range of D was determined in 14 patients by applying experimental data to the model. The calculations on the variables show, that the advantage of this method is its applicability to any experimental case by simply adapting the input data to the recordings.

Blood Circulation

Relationships between mean velocity of circumferential fiber shortening (VCF) and heart rate - the diagnostic value of a normalization of VCF to heart rate.

Previous studies relating mean velocity of circumferential fiber shortening (VCF) to heart rate suggested a linear correlation. Since there is considerable variability in the heart rate of normal subjects and in patients with myocardial disease, a normalization of VCF to heart rate could possibly increase the reliability of this echocardiographic parameter of myocardial function. In 106 normal subjects, a linear correlation between VCF and heart rate was confirmed (r=0.87). Values normalized to an arbitrary heart rate of 60/min by the calculated regression were called "relative velocity of contraction" (RVC). Because of the independence of RVC from heart rate, the RVC shows an obviously smaller physiological variation than VCF. Two hundred seventy-six patients were grouped and classified according to hemodynamic and angiographic parameters. These parameters correlated closer to RVC than to VCF. In addition, RVC gave definitely superior diagnostic information in separating patients with cardiac abnormality from normal individuals than did VCF.

Echocardiography

[Radiocardiographic procedures during the first passage of an intravascular tracer in diagnostic context with echo- and angiocardiography (author's transl)].

In 107 patients having coronary artery disease in their majority, left ventricular ejection fraction and minimal cardiac transit times (MTT) were determined by precordial registration during the first passage of the radioactive tracer. 87 patients underwent echocardiographic examination. Data were compared with ventriculography and coronarography: left ventricular ejection fraction, if radiographically evaluated, shows a low sensitivity in indicating myocardial disorder. MTTs are reduced in more than 80% of patients with CAD at rest. With a few exceptions, all patients with disorders in the ventriculogram show reduced MTT values. MTTs, however, do not react specifically for myocardial performance. They also indicate disorders of central hemodynamics caused by vitia cordis. In these cases myocardial function can not be evaluated. Echocardiography can only be applied in about 85% of patients. It possesses a high sensitivity in discrimination of lower degree failures. Results are misleading in old infarctions with dyskinesia. It is concluded that best diagnostic information concerning global myocardial function results if direct hemodynamic parameters as MTT are combined with echocardiography.

Angiocardiography

[Experimental coronary bypass operation: distribution of myocardial blood flow early and after one year].

In 10 dogs a stenosis greater than 75% of the left circumflex coronary artery is induced (Ameroid) in the course of 40 days. Within 1 hour after coronary artery bypass operation (n = 6) maldistribution of myocardial blood flow (MBF), consisting of a subendocardial perfusion deficit, is improved but not completely abolished. One year after coronary bypass operation (n = 4) MBF and its endo/epi-distribution is normal. Bypass flow and its flow profile are useful indicators of MBF and its intramyocardial distribution only when coronary dilation is induced.

Animals