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PubMedDate not supplied

Consideration of perfusion reserve in viability assessment by myocardial Tl-201 rest-redistribution SPECT: a quantitative study with dual-isotope SPECT.

BACKGROUND: To optimize the use of thallium 201 rest-redistribution study in Tl-201/technetium 99m sestamibi dual-isotope single photon emission computed tomography (SPECT), the predictability of Tl-201 rest-redistribution for viable myocardium was examined according to the degree of perfusion reserve. METHODS AND RESULTS: Twenty patients with both unstable angina and left ventricular dysfunction were enrolled. Tl-201 rest-dipyridamole stress Tc-99m sestamibi gated SPECT/Tl-201 24-hour redistribution SPECT was performed before and 3 months after coronary artery bypass grafting. Through use of a 20-segment model, segmental stress perfusion, rest perfusion, and systolic thickening were quantified on gated SPECT by means of automatic quantitation software. Perfusion was expressed as the average percentage of maximal radioactivity uptake. To represent perfusion reserve, the perfusion difference score (PDS) was defined as rest perfusion minus stress perfusion. A low PDS indicated little or no inducible ischemia, and a high PDS indicated inducible ischemia. In dysfunctional myocardium, viability was defined by the improvement of thickening after coronary artery bypass grafting. The overall predictability of Tl-201 redistribution for viability was 0.709 of the area under the curve (AUC) in receiver operating characteristic analysis. With a cutoff of 7, predictability was significantly better in the low PDS group (AUC = 0.785) than in the high PDS group (AUC = 0.582). CONCLUSIONS: The predictability of Tl-201 rest-redistribution for viability differs according to perfusion reserve. It was more reliable for dysfunctional myocardium with persistent perfusion decrease. On the basis of the continuum hypothesis of chronic stunning and hibernation, we suggest that dysfunctional myocardium with persistent perfusion decrease should be assessed by Tl-201 redistribution SPECT.

Aged↗
PubMed1992

The correlation between three methods of skin perfusion pressure measurement: radionuclide washout, laser Doppler flow, and photoplethysmography.

The most accurate measurement of skin perfusion pressure is made with use of radioisotopic clearance techniques. We compared the skin perfusion pressure using radioisotope to the skin perfusion pressure measured simultaneously by placing laser Doppler and photoplethysmography probes within a transparent polyvinylchloride plastic blood pressure cuff in 13 subjects. A new device, which was created for this experiment, consisted of a plastic bladder into which light-emitting probes can be placed, so that the pressure applied to the skin was transmitted by the surface of the bladder, rather than by the surface of a rigid probe. The cuff was inflated to a supra-systolic pressure over the intradermal injection site of technetium Tc 99m, then deflated in 10 mm Hg decrements at 3-minute intervals. The pressures at which radioisotope clearance began, at which microcirculatory flow was detected by laser Doppler, and at which deflection of the photoplethysmography (DC mode) output occurred, were recorded as the skin perfusion pressure. The range of radioisotopic determined skin perfusion pressure was 0 to 100; skin perfusion pressure-laser Doppler was 0 to 100; and skin perfusion pressure-photoplethysmography was 60 to 100, with 7 of 13 limbs demonstrating no clear deflection point and thus an unobtainable skin perfusion pressure-photoplethysmography reading. Linear regression revealed a coefficient of correlation of 0.991 for skin perfusion pressure when the radioisotopic and laser Doppler methods were compared. Our study is not in agreement with previous reports of the successful determination of skin perfusion pressure with use of photoplethysmography. This may be due to differences in our technique when compared with previous reports of skin perfusion pressure-photoplethysmography determination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1983

Uptake of lipoproteins by in situ perfused rat ovaries: identification of binding sites for high density lipoproteins.

We have examined the uptake and distribution of 125I-labeled human high density lipoprotein, apolipoprotein E-free (hHDL3), 125I-rat high density lipoprotein (HDL), and human HDL (hHDL) reconstituted with [3H]cholesteryl linoleate after their in situ vascular perfusion to ovaries of gonadotropin-primed immature rats on days 6-9 post human chorionic gonadotropin (hCG)-injection. Some rats were treated with 4-aminopyrazolopyrimidine to reduce plasma lipoproteins and ovarian cholesteryl ester stores. Perfused ovaries were analyzed biochemically and autoradiographically, and progestin content of the ovarian effluent was quantified. Infusion of ovine luteinizing hormone and hHDL increased ovarian progestin secretion severalfold, indicating that the perfused ovary was functional. After perfusion with HDL reconstituted with [3H]cholesteryl linoleate, radioactive progestin appeared in the effluent; thus, sterol carried by exogenous HDL was converted to steroid. At 37 degrees C, uptake of 125I-hHDL3 was greatest after 15 min of perfusion with label. This was decreased by 80% when the perfusion was carried out at 4 degrees C and by 70-95% when excess unlabeled hHDL, but not human low density lipoprotein (hLDL), was included in the perfusate with 125I-hHDL. Aminopyrazolopyrimidine treatment enhanced 125I-hHDL uptake twofold. After perfusion for 15 min with 125I-hHDL3, radioactivity in the ovary was high for 3-30 min of HDL-free wash, then declined 75% by 30-60 min. With light and electron microscope autoradiography, 125I-hHDL3 was localized to corpora lutea, both along luteal cell surfaces and over their cytoplasm. The plasma membrane grains appeared to be associated with segments that lacked bristle coats. Perfusion with 125I-rat HDL produced a similar pattern of labeling. In ovaries perfused with 125I-BSA, silver grains were concentrated over macrophage-like cells but were sparse over luteal cells. We conclude that the in situ perfused rat ovary takes up 125I-hHDL3 by a temperature-dependent, lipoprotein-specific process, and that this lipoprotein is accumulated by luteal cells.

Adenine↗
PubMed1998

Perfusion and thermal field during hyperthermia. Experimental measurements and modelling in recurrent breast cancer.

Recurrences of malignant tumours in the chest wall are proposed as a valuable model of tissue mainly perfused by small size vessels (the so-called 'phase III' vessels). Invasive thermal measurements have been performed on two patients affected by cutaneous metastasis of malignant tumours during hyperthermic sessions. Thermal probes were inserted into catheters implanted into the tissue at different depths. In one of the catheters a probe connected with laser-Doppler equipment was inserted to assess blood perfusion in the tumour periphery. The perfusion was monitored throughout the sessions, and a noticeable temporal variability was observed. The effect of the perfusion on the thermal map in the tissue was evaluated locally and the 'effective conductivity' of the perfused tissue was estimated by means of the numerical integration of the 'bio-heat' equation. The tumour temperature, at the site where the perfusion probe is located, can be predicted by the numerical model provided two free parameters, alpha and beta, are evaluated with a fitting procedure. Alpha is related to the effective conductivity and beta to the SAR term of the bio-heat equation. The model aimed at estimating the 'effective conductivity' K(eff) of the perfused tissue, and average values of K(eff) of 0.27 +/- 0.03 W m(-1) degrees C(-1) in Patient 1 and of 0.665 +/- 0.005 W m(-1) degrees C(-1) in Patient 2 were obtained throughout the treatment. However, when the average temperature in a larger tumour volume is to be predicted but only a single, 'local' measurement of the perfusion is available and is assumed to be representative for the whole region, the model results are far less satisfactory. This is probably due to the fact that changes of blood perfusion throughout hyperthermic sessions occur to different extents within the tumour volume, and the differences in perfusion cannot be ignored. The above result suggests that, in addition to the 'temperature map', also a 'perfusion map' within the heated volume should be monitored routinely throughout hyperthermic sessions.

Breast Neoplasms↗
PubMed2002

Cerebral perfusion SPET correlated with Braak pathological stage in Alzheimer's disease.

Reductions in regional cerebral perfusion, particularly in the posterior temporo-parietal lobes, are well recognized in Alzheimer's disease. We set out to correlate perfusion changes, using (99m)Tc-HMPAO single photon emission tomography (SPET), with the pathological stage of Alzheimer's disease. The 'Braak stage' of the distribution of neurofibrillary pathology in post-mortem brains was used to classify SPET scans taken in life from a mixed (dementia and control) elderly population into the entorhinal stage (n = 23 subjects), limbic stage (n = 30 subjects) and neocortical stage (n = 36 subjects) Alzheimer's disease pathology. The SPET scans were then registered to a common, standard Talaraich space, and single template scans produced for each pathological stage. Comparison of these templates revealed an evolution in the pattern of reduction in regional perfusion. Additional comparisons were performed using earlier SPET scans obtained 5 years before death. For comparisons between templates, a threshold of 10% perfusion change was chosen so as to be clinically relevant as well as statistically significant. Reduced perfusion appears between the entorhinal and limbic stages in the anterior medial temporal lobe, subcallosal area, posterior cingulate cortex, precuneus and possibly the supero-anterior aspects of the cerebellar hemispheres. Large posterior temporo-parietal perfusion defects then appear between the limbic and neocortical stages, before finally large frontal lobe perfusion defects. The time course of these perfusion defects appears relatively long, suggesting that perfusion changes may have scope to be a diagnostic aid in staging Alzheimer's disease in life. The reduction in anterior medial temporal lobe perfusion may have future relevance on modern high resolution SPET and PET systems and also perfusion-type MRI sequences.

Aged↗
PubMedDate not supplied

Technetium-99m-labeled myocardial perfusion agents: Are they better than thallium-201?

Currently, thallium-201 (201Tl)- and technetium-99m (99mTc)-labeled tracers are used interchangeably for the detection of coronary artery disease, the assessment of myocardial viability, and risk stratification. This article reviews some of the potential advantages and disadvantages of the 99mTc-labeled tracers relative to 201Tl. The basic myocardial kinetic properties and biodistribution of the commonly used 99mTc-labeled perfusion tracers are compared with those of 201Tl. The clinical value of the 99mTc-labeled perfusion tracers is then compared with that of 201Tl imaging. With regard to imaging physics and radiation safety, the 99mTc-labeled tracers are superior to 201Tl. Cost and tracer availability also may favor 99mTc-labeled perfusion tracers rather than 201Tl imaging. However, the most widely used 99mTc-labeled perfusion tracers currently approved for clinical use-99mTc-sestamibi and 99mTc-tetrofosmin-do not track myocardial flow as well as 201Tl does. This shortcoming of 99mTc-labeled perfusion tracers may reduce the sensitivity of these agents in detecting subcritical coronary artery disease. The most notable new perfusion agent is 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v), which is considered to be the 99mTc-labeled equivalent of 201Tl. However, 99mTc-labeled bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(v) is a neutral compound with kinetic properties that are very different from those of 201Tl. Myocardial perfusion imaging is often conducted in conjunction with exercise or with different pharmacologic stressors, both of which augment regional flow heterogeneity. Each of these stressors has unique effects on the coronary vasculature and influences the behavior of the radiolabeled perfusion agents. The substantial differences in myocardial uptake, clearance kinetics, and biodistribution between each of the 99mTc-labeled perfusion tracers and 201Tl should be considered in the clinical application of perfusion imaging. The myocardial retention of all of the agents is affected by myocardial viability. However, 201Tl demonstrates greater differential clearance from normal and ischemic regions (redistribution), making 201Tl a better agent for assessment of viability, particularly in patients with extremely low flow. In contrast, agents that do not redistribute, such as 99mTc-tetrofosmin, might be better for acute assessment of "risk areas" or of chest pain. Each of the available perfusion tracers has unique advantages and disadvantages that must be considered to ensure its optimal application.

Coronary Circulation↗
PubMed2002

Effect of liposuction on skin perfusion.

Clinical reports of full-thickness skin necrosis have raised concern about the thermal and dermal ischemic effects of ultrasound-assisted liposuction. The purpose of this study was to evaluate skin perfusion in patients treated with ultrasound-assisted liposuction or suction-assisted liposuction. Patients (n = 75) were studied prospectively in the perioperative period surrounding their suction-assisted liposuction (31 patients) or ultrasound-assisted liposuction (64 patients). The laser Doppler flowmeter was used to monitor skin perfusion in the treated regions preoperatively, intraoperatively, and postoperatively at a series of time intervals. The effects of the anesthetic, wetting solution, and type of liposuction (suction-assisted liposuction or ultrasound-assisted liposuction) on skin perfusion were measured. Anesthetic induction significantly increased measured skin perfusion. Wetting solution infusion significantly decreased skin perfusion (-57.4 percent +/- 2.0) by 15 minutes postinfusion. Skin perfusion in the ultrasound-assisted liposuction group was significantly greater than that of the suction-assisted liposuction patients at 1 hour, 1 day, and 1 week postoperatively; however, by 2 to 5 weeks, no difference in skin perfusion was noted and skin perfusion had returned to preoperative levels in both groups. Although skin perfusion in the suction-assisted liposuction group was significantly lower than in the ultrasound-assisted liposuction group in the early postoperative period, no differences in skin perfusion between the groups were noted beyond 1 week postoperatively, suggesting that neither technique impairs perfusion.

Adolescent↗
PubMed2006

Perfusion zones of the DIEP flap revisited: a clinical study.

BACKGROUND: The Hartrampf perfusion zones of the lower abdominal flap are generally accepted. They were empirically based on the clinical impression of the perfusion in the first 16 unipedicled transverse rectus abdominis musculocutaneous flaps and have been uncritically adopted for the free transverse rectus abdominis musculocutaneous and the free deep inferior epigastric perforator (DIEP) flap. Scientific data proving the validity of these perfusion zones do not exist. The objective of this study was to evaluate and quantitatively assess the perfusion zones of the DIEP flap. METHODS: In a clinical, prospective study of 15 patients undergoing DIEP flap breast reconstruction, tissue perfusion was intraoperatively assessed using the method of laser-induced fluorescence of indocyanine green. RESULTS: Perfusion of zones I, II, and III was seen 25, 41, and 32 seconds, respectively, after injection, and the perfusion index constituted 76, 25, and 47 percent (median) of normal tissue. Perfusion of zone IV was completely absent in five patients (33 percent); in the remaining patients, it was dramatically decreased (5 percent) and occurred with a delay of 67 seconds. CONCLUSIONS: On the basis of the results of this study, the Hartrampf concept of a centrally perfused skin ellipse with declining perfusion of its peripheral ends is wrong and should be revised. Instead, one should think of the lower abdominal flap as two halves separated by the midline. The ipsilateral half has an axial pattern of perfusion; the contralateral half shows a random-pattern, individually variable blood supply. Therefore, the classic Hartrampf zones should be rearranged, switching zones II and III.

Abdominal Wall↗
PubMed1976

Tryptophan metabolism in the isolated perfused liver of the rat: effects of tryptophan concentration, hydrocortisone and allopurinol on tryptophan pyrrolase activity and kynurenine formation.

1 The effect of tryptophan concentration on the rate of kynurenine appearance and tryptophan disappearance in the medium perfused through the isolated liver of the rat has been investigated. The effect of pretreatment of the rat with hydrocortisone or allopurinol was also examined, together with the effects of these treatments on liver tryptophan pyrrolase activity measured in vitro at the beginning and end of perfusion. 2 Hydrocortisone (5 mg/kg) injection 3 h before perfusion resulted in a four-fold increase in kynurenine production by the liver during perfusion with a medium containing either 0.1 mmol/1 or 1.0 mmol/1 tryptophan. Injection of allopurinol (20 mg/kg) together with hydrocortisone and addition of allopurinol (4 mg/100 ml) to the medium abolished the hydrocortisone-induced rise of kynurenine in the 0.1 mmol/tryptophan medium but not the 1.0 mmol/1 tryptophan medium. 3 Injection of cycloheximide (30 mg/kg) with hydrocortisone (5 mg/kg) 3 h before perfusion inhibited the hydrocortisone-induced rise of kynurenine production and the increase in pyrrolase activity measured in vitro both before and at the end of perfusion with 1.0 mmol/1 tryptophan. This last result suggests that protein synthesis is involved not only in hydrocortisone induction of pyrrolase but also in substrate induction. 4 Kynurenine production in the 1.0 mmol/1 tryptophan medium was less in both saline- and hydrocortisone-treated older rats (335-450 g) compared to younger rats (180-220 g). In agreement with a previous study, pyrrolase activity in vitro was also lower in both saline- and hydrocortisone- treated older rats at the beginning of the perfusion although activity had risen equally in both young and older rats at the end of perfusion. 5 There was little correlation between the rate of tryptophan disappearance from the medium and the activity of tryptophan pyrrolase either as measured in vitro or as indicated by the rate of kynurenine production. 6 In general, the production of kynurenine in the medium at the end of the 60 min perfusion was indicative of in vitro pyrrolase activity at the start of the perfusion. 7 It is concluded that while in vitro pyrrolase assay does not give a quantitative index of kynurenne production, it does provide a qualitative index. Furthermore, if kynurenine production in the isolated perfused liver of the rat is indicative of in vivo pyrrolase activity, then hydrocortisone must induce pyrrolase activity in vivo.

Age Factors↗
PubMed1992

Effects of pyridoxalated hemoglobin polyoxyethylene conjugate and stroma free hemoglobin on pulmonary vascular responsiveness to vasoactive substances in isolated perfused rat lungs.

We examined the effects of pyridoxalated hemoglobin polyoxyethylene conjugate (PHP) and stroma free hemoglobin (SFH) on vascular responsiveness to various vasoactive substances in isolated perfused rat lungs. The lungs isolated from rats were perfused with 6% PHP, 6% SFH, or 6% hydroxyethylstarch (HES) solution, and the effects of intrapulmonary arterial injection of norepinephrine (NE), angiotensin II (ANG-II), acetylcholine (ACh), and nitroglycerin (NG) were examined by measuring perfusion pressure. NE and ANG-II produced a dose-dependent increase in perfusion pressure in all groups. The NE response in the PHP- or SFH-perfused group was significantly larger than that in the HES-perfused one. ACh decreased perfusion pressure in both PHP- and HES-perfused groups but increased perfusion pressure in the SFH-perfused group. NG decreased perfusion pressure in all groups. Present results indicate that pulmonary arterial responses to endothelium-derived relaxing factor (EDRF) induced by ACh would not be affected in the presence of PHP.

Acetylcholine↗
PubMed2004

Assessment of pigmented skin lesions in terms of blood perfusion estimates.

BACKGROUND/AIMS: Cutaneous malignant melanoma is a disease of increasing clinical and economical importance. The prognosis is good with early diagnosis. The chief differential diagnosis is benign melanocytic naevus, a common lesion in Caucasians. Attempts have been made to use bioengineering techniques to aid in the initial diagnosis. The present study proposes a method of extracting possibly discriminative blood perfusion properties in pigmented skin lesions by combining information on the lesions' blood perfusion with optical or visual information of their spatial extent. METHODS: A total of 46 blood perfusion measurements were performed on 22 pigmented skin lesions, the ultimate diagnosis of which was three histologically proven malignant melanomas, four histologically proven benign naevi and fifteen naevi assessed by two specialist dermatologists as being benign. Laser Doppler perfusion imaging gave two different types of two-dimensional data sets (64x64 pixels), one representing the total backscattered light intensity at each measurement point (TLI image) and the second corresponding to perfusion values. The boundaries of each examined lesion were derived from the TLI image employing greyscale thresholding, thus resulting in an estimated region of interest (ROI) approximating the optical extent of the lesion. The ROI was superimposed on the perfusion image and extraction of perfusion features was then performed. RESULTS: The processing of the TLI images was successful in delineating the lesions' boundaries. The first hypothesis that the mean perfusion quotients in MM and benign naevi are equal could not be rejected at the chosen 5% level of significance. The second hypothesis that the mean percent-age of elevated perfusion values (image pixels) within the ROI shows no difference between MM and benign naevi could be rejected at a 5% level of significance. CONCLUSIONS: This study has presented a method of extracting blood perfusion parameters of pigmented skin lesions by combining blood perfusion information with information on the lesion's optical extent. The proposed method of presenting data could prove to be a useful discriminative adjunct in the assessment of pigmented skin lesions.

Adult↗
PubMed2003

Regional myocardial perfusion defects during exercise, as assessed by three dimensional integration of morphology and function, in relation to abnormal endothelium dependent vasoreactivity of the coronary microcirculation.

OBJECTIVE: To test the hypothesis that scintigraphic regional myocardial perfusion defects during exercise in patients with normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory in response to cold pressor testing. METHODS: 38 patients were classified into two groups according to the presence or absence of exercise induced scintigraphic myocardial perfusion defects. A cold pressor test was done in all patients during routine coronary angiography, followed by dynamic positron emission tomography to establish coronary blood flow mediated vasoreactivity of the epicardial coronary artery and the myocardial territories supplied by the left anterior descending, left circumflex, and right coronary arteries. RESULTS: 28 patients had regional myocardial perfusion defects while 10 had normal scintigraphic imaging. The three dimensional scintigraphic fusion image revealed 49 regional myocardial perfusion defects with a mean (SD) reversibility of the original stress defect of 20 (3)%. In patients with exercise induced regional myocardial perfusion defects, the responses of epicardial luminal area and regional myocardial blood flow (RMBF) to cold pressor testing were reduced compared with patients with normal perfusion imaging (epicardial luminal area: 5.2 (1.2) to 4.2 (0.86) mm2 v 4.7 (0.5) to 5.8 (0.5) mm2; RMBF: 0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.15) to 1.38 (0.26) ml/g/min; p < or = 0.03, respectively). In patients with regional abnormal scintigraphic perfusion, the corresponding RMBF response to cold pressor testing was more severely impaired than the mean myocardial blood flow in the remaining two vascular territories, but the difference was not significant (0.75 (0.16) to 0.78 (0.20) ml/g/min v 0.75 (0.10) to 0.87 (0.12) ml/g/min; NS). The endothelium independent increase in RMBF induced by glyceryl trinitrate did not differ between patients with exercise induced myocardial perfusion defects and those with normal perfusion images (0.75 (0.16) to 0.94 (0.09) ml/g/min v 0.75 (0.15) to 0.94 (0.09) ml/g/min; NS). There was a highly significant correlation between the endothelium dependent responses of RMBF to cold pressor testing and the severity of exercise induced scintigraphic regional myocardial perfusion defects (r = 0.95, p = 0.001). CONCLUSIONS: Exercise induced scintigraphic regional myocardial perfusion defects in patients with angina but normal coronary angiography may be related to abnormal endothelium dependent vasoreactivity of the corresponding myocardial territory.

Cold Temperature↗
PubMed2004

Admission perfusion CT: prognostic value in patients with severe head trauma.

PURPOSE: To assess the prognostic value of admission perfusion computed tomography (CT) in patients with severe head trauma. MATERIALS AND METHODS: This prospective study included 130 patients with severe trauma, aged 19-86 years, admitted with a Glasgow Coma Scale score of 8 or less. They underwent perfusion CT as part of their admission CT survey. Clinical data, unenhanced cerebral CT findings, and perfusion CT scans were evaluated with respect to the Glasgow Outcome Scale (GOS) score at 3 months. Perfusion CT features were evaluated in patients with intracranial hypertension, cerebral contusions, and juxtadural hematomas. Ordered logistic regression was used to determine risk factors for an unfavorable GOS score at 3 months. RESULTS: Perfusion CT was more sensitive than conventional unenhanced CT in the detection of cerebral contusions. Perfusion CT featured specific patterns with respect to patient outcome, with normal brain perfusion or hyperemia in patients with favorable outcome, and oligemia in patients with unfavorable outcome. The number of arterial territories with low regional cerebral blood volume at perfusion CT was an independent prognostic factor (P =.008), as were mean arterial pressure at the scene of accident (P =.083), base excess at admission (P =.002), presence of skull fractures (P =.041), and signs of herniation (P =.013) at admission unenhanced cerebral CT. Perfusion CT also showed a range of brain perfusion alterations in patients with juxtadural collections, cerebral edema, or intracranial hypertension. CONCLUSION: Perfusion CT in patients with severe head trauma provides independent prognostic information regarding functional outcome.

Adult↗
PubMed1993

Quantification of regional myocardial perfusion with generator-produced 62Cu-PTSM and positron emission tomography.

BACKGROUND: Noninvasive assessment of regional myocardial perfusion at rest and after stress is important for the objective evaluation of the effects of coronary artery disease and its response to therapy. Centers that do not have cyclotrons rely on generator-produced radioisotopes for assessment of regional myocardial perfusion with positron emission tomography (PET). The aim of the present study was to develop and implement an approach to quantify regional myocardial perfusion using copper(II) pyruvaldehyde bis-(N4-thiosemicarbazone) (PTSM) labeled with the generator-produced, positron-emitting radionuclide 62Cu (t1/2 = 9.7 minutes). METHODS AND RESULTS: Regional perfusion was estimated from dynamic PET scans after intravenous administration of 62Cu-PTSM in 21 studies in 13 intact dogs evaluated over a wide range of myocardial flow values. In 15 interventions in nine dogs, regional perfusion was also estimated with H2(15)O. Regional perfusion with 62Cu-PTSM was estimated from dynamic blood and tissue time-activity curves, along with the model parameter k1 (forward rate of transport) and the PET parameter FBM (fraction of blood pool activity observed in tissue), using a two-compartment kinetic model. Arterial blood activity was corrected for red blood cell-associated 62Cu. In 44 comparisons, estimates of regional perfusion with 62Cu-PTSM correlated well with estimates obtained with concomitantly administered radiolabeled microspheres (y = 0.90x +/- 0.15, r = 0.95, p < 0.05) over a flow range from 0.23 to 6.14 ml/g per minute. In five healthy human volunteers evaluated at rest with H2(15)O and 62Cu-PTSM, regional perfusion estimated with 62Cu-PTSM was not significantly different from that obtained with H2(15)O (1.05 +/- 0.36 versus 0.96 +/- 0.28 ml/g per minute). 62Cu-PTSM provided high-quality images of the heart. CONCLUSIONS: The results of this study demonstrate that quantification of regional myocardial perfusion is feasible using generator-produced 62Cu-PTSM. Since 62Cu-PTSM can be used to estimate perfusion in the brain, kidney, and tumors as well as in the heart, it is an attractive tracer for centers that rely on generator-produced tracers for the evaluation of perfusion with PET.

Animals↗
PubMed1997

Alternations in beta-Adrenoceptor Mechanisms in Hearts Perfused With Xanthine Plus Xanthine Oxidase.

BACKGROUND: Although beta-adrenoceptors and adenylyl cyclase are known to be affected upon exposing cardiac membranes to some oxyradical generating systems, the results are conflicting. Furthermore, functional significance of alterations in the beta-adrenoceptor-adenylyl cyclase systems in terms of changes in the inotropic responses to catecholamines is not clear. METHODS AND RESULTS: The positive inotropic effect of isoproterenol was augmented on perfusing the isolated rat hearts with xanthine (X) plus xanthine oxidase (XO) for 5 minutes but was attenuated by perfusion for 15 minutes. The isoproterenol-stimulated adenylyl cyclase activity in cardiac membranes showed an increase at 10 minutes and a decrease at 30 minutes perfusion of hearts with X plus XO. The density of beta-adrenoceptors in cardiac membraners was reduced after 10 minutes and 30 minutes of perfusion with X plus XO, whereas the affinity of beta-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although beta-adrenoceptors was increased after 10 minutes and reduced after 30 minutes. Although beta-adrenoceptors were unaltered by 10 minutes of perfusion with X plus XO, their affinity was increased and density was decreased by 30 minutes of perfusion. The agonist competition curves using isoproterenol indicated an increase in the number of coupled receptors in the high affinity state on 10 minutes of perfusion and an increase in the low affinity state of coupled receptor due to 30 minutes of perfusion with X plus XO. The basal as well as forskolin-, NaF- and Gpp(NH)p-stimulated adenylyl cyclase activities in cardiac membranes exhibited an increase after 10 minutes and decrease after 30 minutes of perfusion with X plus XO. Although the presence of superoxide dismutase plus catalase in the perfusion medium prevented most of the alterations due to X plus XO, it did not alter the increased affinity of the beta-adrenoceptor upon perfusing hearts for 10 minutes with X plus XO. CONCLUSIONS: The results in this study suggest the biphasic nature of the oxyradical-induced alterations in both the inotropic responses to catecholamines and the beta-adrenoceptor-mediated signal transduction mechanism in the heart.

Journal Article↗
PubMed2006

Frequency and severity of myocardial perfusion abnormalities using Tc-99m MIBI SPECT in cardiac syndrome X.

BACKGROUND: Cardiac syndrome X is defined by a typical angina pectoris with normal or near normal (stenosis <40%) coronary angiogram with or without electrocardiogram (ECG) change or atypical angina pectoris with normal or near normal coronary angiogram plus a positive none-invasive test (exercise tolerance test or myocardial perfusion scan) with or without ECG change. Studies with myocardial perfusion imaging on this syndrome have indicated some abnormal perfusion scan. We evaluated the role of myocardial perfusion imaging (MPI) and also the severity and extent of perfusion abnormality using Tc-99m MIBI Single Photon Emission Computed Tomography (SPECT) in these patients. METHODS: The study group consisted of 36 patients with cardiac syndrome X. The semiquantitative perfusion analysis was performed using exercise Tc-99m MIBI SPECT. The MPI results were analyzed by the number, location and severity of perfusion defects. RESULTS: Abnormal perfusion defects were detected in 13 (36.10%) cases, while the remaining 23 (63.90%) had normal cardiac imaging. Five of 13 (38.4%) abnormal studies showed multiple perfusion defects. The defects were localized in the apex in 3, apical segments in 4, midventricular segments in 12 and basal segments in 6 cases. Fourteen (56%) of all abnormal segments revealed mild, 7(28%) moderate and 4 (16%) severe reduction of tracer uptake. No fixed defects were identified. The vessel territories were approximately the same in all subjects. The Exercise treadmill test (ETT) was positive in 25(69%) and negative in 11(30%) patients. There was no consistent pattern as related to the extent of MPI defects or exercise test results. CONCLUSION: Our study suggests that multiple perfusion abnormalities with different levels of severity are common in cardiac syndrome X, with more than 30 % of these patients having at least one abnormal perfusion segment. Our findings suggest that in these patients microvascular angina is probably more common than is generally believed.

Journal Article↗
PubMed1989

Aldosterone metabolism in the isolated perfused liver of female and male rats.

A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes. Perfusate 4-14C-labeled radiometabolites after 90 min of perfusion were lower in livers of castrated male rats than in noncastrated male rats (P less than 0.001). The final perfusate 14C-labeled radiometabolite concentration correlated inversely with the total 14C in bile (P less than 0.01). All 14C-labeled radiometabolites detected in perfusate and bile after 90 min were more polar than aldosterone. After enzymatic hydrolysis, some of the metabolites from the male livers cochromatographed with tetrahydro- and dihydroaldosterone, while other fractions remained more polar. Only more polar metabolites were detected in the perfusate and bile of female livers.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗
PubMed2003

Effects of dopexamine and positive end-expiratory pressure on intestinal blood flow and oxygenation: the perfusion pressure perspective.

OBJECTIVE: To evaluate the net effects of the concomitant use of positive end-expiratory pressure (PEEP) and dopexamine on intestinal tissue perfusion and oxygenation during predefined artificial reductions in intestinal perfusion pressure (IPP). DESIGN: Prospective, self-controlled, experimental study. SETTING: University hospital research laboratory. SUBJECTS: Seven female pigs. MEASUREMENTS: In barbiturate-anesthetized pigs, we measured mesenteric blood flow (QMES) [by transit-time ultrasonic flowmetry], jejunal mucosal perfusion (by laser Doppler flowmetry), and tissue PO(2) (by microoximetry). Based on blood sampling, we calculated the intestinal net lactate production and oxygenation. INTERVENTIONS: These measurements and calculations were performed at three predefined and controlled IPP levels, which were obtained by an adjustable clamp around the superior mesenteric artery. At each IPP level, measurements were performed prior to and during PEEP (10 cm H(2)O), both with and without simultaneous dopexamine infusions (at 0.5 and 1.0 microg/kg/min). RESULTS: Within the IPP range of 77 to 33 mm Hg, intestinal perfusion and oxygenation were maintained irrespective of whether PEEP and/or dopexamine were applied or not. At IPP < 33 mm Hg, QMES and intestinal oxygenation deteriorated, resulting in regional net lactate production. At this IPP range, tissue oxygen perfusion was entirely pressure-dependent, and even small reductions in IPP led to prominent increases in intestinal net lactate production. Dopexamine did not modify this pattern. CONCLUSIONS: We describe maintained intestinal tissue oxygen perfusion within a wide perfusion pressure range. Within this perfusion pressure range, PEEP did not induce any adverse regional circulatory effects. Below the perfusion pressure range for effective autoregulation, intestinal tissue oxygen perfusion deteriorated, and regional ischemia occurred. In this situation, dopexamine was unable to counteract IPP-dependent decreases in intestinal tissue oxygen perfusion. The regional ischemic threshold can be defined either as an IPP of < 33 mm Hg or as an intestinal tissue PO(2) of < 45 mm Hg.

Adrenergic beta-Agonists↗