Biomedical subjects

S R Bergmann

Publications and source records attributed to S R Bergmann.

At least 91 records · Page 5Linked to original sources

PubMed1989

Assessment of myocardial oxidative metabolic reserve with positron emission tomography and carbon-11 acetate.

We have previously demonstrated that positron emission tomography (PET) with [11C]acetate allows noninvasive regional quantification of myocardial oxidative metabolism. To assess the metabolic response of normal myocardium to increased work (oxidative metabolic reserve), clearance of myocardial 11C activity after administration of [11C]acetate i.v. was measured with PET in seven normal subjects at rest and during dobutamine infusion. At rest, clearance of 11C was monoexponential and homogeneous. The rate constant of the first phase of 11C clearance, k1, averaged 0.054 +/- 0.014 min-1 at a rate-pressure produce (RPP) of 7329 +/- 1445 mmHg X bpm. During dobutamine infusion, RPP increased by an average of 141% to 17,493 +/- 3582 mm Hg Z bpm. Clearance of 11C became biexponential and remained homogeneous. k1 averaged 0.198 +/- 0.043 min-1 with a mean coefficient of variation of 16%.. k1 and RPP correlated closely (r = 0.91; p less than 0.001), and the slope of the k1/RPP relation remained consistent in all subjects (1.48 +/- 0.42). These findings suggest that PET with [11C]acetate and dobutamine stress may provide a promising approach for evaluation of regional myocardial oxidative metabolic reserve in patients with cardiac diseases of diverse etiologies and for assessment of the efficacy of interventions designed to enhance the recovery of metabolically comprised myocardium.

Acetates↗

PubMed1989

Noninvasive estimation of regional myocardial oxygen consumption by positron emission tomography with carbon-11 acetate in patients with myocardial infarction.

We previously demonstrated in experimental studies that myocardial oxygen consumption (MVO2) can be estimated noninvasively with positron emission tomography (PET) from analysis of the myocardial turnover rate constant (k) after administration of carbon-11 (11C) acetate. To determine regional k in healthy human subjects and to estimate alterations in MVO2 accompanying myocardial ischemia, we administered [11C]acetate to five healthy human volunteers and to six patients with myocardial infarction. Extraction of [11C]acetate by the myocardium was avid and clearance from the blood-pool rapid yielding myocardial images of excellent quality. Regional k was homogeneous in myocardium of healthy volunteers (coefficient variation = 11%). In patients, k in regions remote from the area of infarction was not different from values in myocardium of healthy human volunteers (0.061 +/- 0.025 compared with 0.057 +/- 0.008 min-1). In contrast, MVO2 in the center of the infarct region was only 6% of that in remote regions (p less than 0.01). In four patients studied within 48 hr of infarction and again more than seven days after the acute event, regional k and MVO2 did not change. The approach developed should facilitate evaluation of the efficacy of interventions designed to enhance recovery of jeopardized myocardium and permit estimation of regional MVO2 and metabolic reserve underlying cardiac disease of diverse etiologies.

Acetates↗

PubMed1989

Kinetics of copper-PTSM in isolated hearts: a novel tracer for measuring blood flow with positron emission tomography.

Copper(II) pyruvaldehyde bis(N4-methylthiosemicarbazone) ([Cu]PTSM) has shown potential as a flow tracer and can be labeled with the generator-produced positron emitting radionuclide 62Cu as well as with other copper radioisotopes. To define the myocardial handling of [Cu]PTSM, the externally detected single pass extraction and retention of [67Cu]PTSM was characterized after bolus administration in 12 isolated rabbit hearts perfused with erythrocyte-enriched modified Krebs-Henseleit buffer which permitted physiologic flow rates. The myocardial residual (extraction) fraction at control flow rates (approximately 1.5 ml/g/min) was 45 +/- 7(s.d.)% (n = 12), and was invariate with ischemia (flow = 0.15 ml/g/min, n = 4), hyperemia (flow = 3 ml/g/min, n = 4) or with hypoxia induced by perfusion at control flow rates with hypoxic buffer (n = 4) (residual fraction 45 +/- 20, 43 +/- 8, and 49 +/- 8%, respectively, p = N.S.). Once extracted, the tracer was retained with a biologic t1/2 of greater than 3600 min in all groups. The high single-pass extraction, which is not influenced by flow, and the prolonged retention of this tracer under diverse conditions indicate that [Cu]PTSM could be a useful tracer for measuring blood flow with positron emission tomography.

Animals↗

PubMed1988

Sensitivity of scintigraphy with 111In-lymphocytes for detection of cardiac allograft rejection.

We recently demonstrated the feasibility of noninvasive detection of cardiac allograft rejection after administration of indium-111-labeled lymphocytes. To determine the sensitivity and specificity of the technique, as well as its value for delineating the severity of rejection, we studied 16 dogs with heterotopic thoracic cardiac allografts. Five animals were evaluated while exposed to immunosuppressive agents. Animals were scanned sequentially after administration of 100-400 microCi of indium-111-labeled autologous lymphocytes. Myocardial lymphocyte infiltration was expressed as the indium excess (IE), defined as the ratio of indium activity of the transplant or native heart compared with that in blood. Scintigraphic results were compared with characteristics of simultaneously obtained endomyocardial biopsies. Among 17 biopsy documented episodes of rejection, 16 were detected scintigraphically. Among 18 biopsies with no evidence of rejection, scintigraphy was uniformly negative. Thus, the sensitivity and specificity of scintigraphy were 94 and 100%, respectively. Biopsies graded as showing no rejection were associated with an IE of 0.3 +/- 0.5 (+/- SD); those graded as mild, 2.8 +/- 1.7; those as moderate, 10.7 +/- 7.2; and those graded as indicative of severe rejection, 14.2 +/- 4.5. Thus, scintigraphy with indium-111-labeled lymphocytes sensitively and specifically detects cardiac allograft rejection and delineates the intensity of the rejection process. It should be useful clinically for assessing potential allograft rejection noninvasively.

Animals↗

PubMed1988

Noninvasive assessment of canine myocardial oxidative metabolism with carbon-11 acetate and positron emission tomography.

Noninvasive quantification of regional myocardial metabolism would be highly desirable to evaluate pathogenetic mechanisms of heart disease and their response to therapy. It was previously demonstrated that the metabolism of radiolabeled acetate, a readily utilized myocardial substrate predominantly metabolized to carbon dioxide (CO2) by way of the tricarboxylic acid cycle, provides a good index of oxidative metabolism in isolated perfused rabbit hearts because of tight coupling between the tricarboxylic acid cycle and oxidative phosphorylation. In the present study, in a prelude to human studies, the relation between myocardial clearance of carbon-11 (11C)-labeled acetate and myocardial oxygen consumption was characterized in eight intact dogs using positron emission tomography. Anesthetized dogs were studied during baseline conditions and again during either high or low work states induced pharmacologically. High myocardial extraction and rapid blood clearance of tracer yielded myocardial images of excellent quality. The turnover (clearance) of 11C radioactivity from the myocardium was biexponential with the mean half-time of the dominant rapid phase averaging 5.4 +/- 2.2, 2.8 +/- 1.3 and 11.1 +/- 1.3 min in control, high and low work load studies, respectively. No significant difference was found between the rate of clearance of 11C radioactivity from the myocardium measured noninvasively with positron emission tomography and the myocardial efflux of 11CO2 measured directly from the coronary sinus. The rate of clearance of the 11C radioactivity from the heart correlated closely with myocardial oxygen consumption (r = 0.90, p less than 0.001) as well as with the rate-pressure product (r = 0.95, p less than 0.001). Hence, the rate of oxidation of 11C-acetate can be determined noninvasively with positron emission tomography, providing a quantitative index of oxidative metabolism under diverse conditions.

Acetates↗

PubMed1988

Compromise of beneficial effects of reperfusion on myocardium supplied by vessels with critical residual stenosis.

Coronary thrombolysis in patients frequently unmasks high grade residual stenosis. To determine whether beneficial effects of reperfusion are compromised by critical residual coronary stenosis, 14 dogs were instrumented with an external left anterior descending coronary artery balloon occluder, Doppler flow probe and adjustable screw clamp. In eight of the dogs, critical stenosis (abolition of reactive hyperemia after a 20 s occlusion; 95.7 +/- 1.0% cross-sectional area reduction) was induced before occlusion and maintained. In the control group (n = 6), no stenosis was induced. Each dog was subjected to 2 h of myocardial ischemia followed by balloon deflation and 24 h of reperfusion. Myocardial blood flow assessed with microspheres was similar during balloon inflation in both groups and indicative of profound ischemia. Transmural blood flow to the reperfused zone assessed 1 min after balloon deflation was significantly greater in control dogs without residual stenosis (383% of normal compared with 120% of normal in dogs with stenosis) (p less than 0.01). Compromise of transmural flow persisted in dogs with stenosis (85% compared with 121% of normal in control dogs after 1 h, p less than 0.05; and 49% compared with 68% after 24 h of reperfusion, p less than 0.05). Diminution of subendocardial blood flow after reperfusion was particularly marked. The extent of infarction was greater in the heart of dogs with residual stenosis. Thus, residual critical coronary stenosis compromises nutritional perfusion and salvage of reperfused myocardium after recanalization. These observations underscore the need for prompt identification of patients with high grade residual stenosis early after coronary thrombolysis and the potential value of angioplasty or coronary surgery in selected patients soon after initial recanalization.

Angioplasty, Balloon↗

PubMed1988

Noninvasive assessment of treatment of cardiac allograft rejection with indium-111-labeled lymphocytes.

We have shown previously that cardiac allograft rejection can be detected noninvasively with gamma scintigraphy after administration of indium-111 (111In)-labeled lymphocytes. To determine whether this technique could be used to monitor salvage immunosuppressive therapy in reversing rejection, 5 dogs were studied after thoracic heterotopic cardiac transplantation. Initial postoperative immunosuppression was maintained with cyclosporine (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 7 days after transplantation and then discontinued. Scintigraphy after administration of labeled lymphocytes was performed during initial immunosuppression and every 3 days after its termination. Endomyocardial biopsies were obtained on each day scintigraphy was performed. Once scintigraphic criteria for rejection were met (111In-lymphocyte uptake greater than mean +/- 2SD of normal myocardium), animals were treated with high dose methylprednisolone and cyclosporine. Myocardial 111In-lymphocyte activity compared with that in blood was 0.7 +/- 0.8 during initial immunosuppression, increased to 5.7 +/- 3.5 after termination of therapy (P less than 0.01), and diminished with salvage immunosuppressive therapy to 0.5 +/- 0.8 (P = NS compared with native hearts or allografts during initial immunosuppression). Scintigraphy accurately predicted all but one episode of biopsy-documented rejection and accurately detected reversal of rejection during salvage. Thus, scintigraphy with 111In-labeled lymphocytes should facilitate noninvasive monitoring of antirejection therapy in patients.

Animals↗

PubMed1988

Delineation of impaired regional myocardial perfusion by positron emission tomography with H2(15)O.

Positron emission tomography with 15O-labeled water (H2(15)O) can be used to delineate abnormal regional myocardial blood flow in experimental animals. To determine the feasibility of this method in humans, we studied 33 subjects (9 normal volunteers and 24 patients with angiographically documented coronary artery disease) at rest and after myocardial hyperemia induced with intravenous infusion of dipyridamole. At rest, the myocardial region demonstrating the lowest relative H2(15)O activity exhibited 71 +/- 8% of activity in the region with peak activity in control subjects and 62 +/- 17% in patients (p = NS). After the dipyridamole infusion, differences between the two groups were accentuated. In control subjects, activity in the region with lowest relative radioactivity averaged 77 +/- 5% of that in the region with peak activity. In patients, it averaged 55 +/- 22% of activity in the region with peak activity (p less than 0.01). Results in patients with ischemia with or without a history of remote myocardial infarction were not significantly different. In 22 of the 24 patients, the region with lowest relative perfusion corresponded anatomically to the region of myocardium distal to a stenosis. Thus, delineation of regional myocardial perfusion in patients with coronary artery disease is possible with positron emission tomography and H2(15)O. Further studies will be necessary to prospectively determine sensitivity and specificity.

Adult↗

PubMed1988

Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy.

Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

Animals↗

PubMed1987

Metabolism of beta-methyl[1-11C]heptadecanoic acid in canine myocardium.

To assess the contributions of metabolism to CO2 and back-diffusion of nonmetabolized tracer to total clearance of beta-methyl[1-11C]heptadecanoic acid ([1-11C]BMHDA) from myocardium and its distribution into lipid pools, 10-15 mCi of [1-11C]BMHDA were rapidly infused into the circumflex coronary artery of seven open-chest dogs. Externally detected clearance of myocardial 11C-activity was protracted (t1/2 = 41 +/- 18 min) with over 50% of extracted tracer retained in tissue after 20 min. Efflux of extracted [1-11C]BMHDA between 5 and 20 min was comprised of both 11CO2 (16.5 +/- 15.2%) and nonmetabolized [11C]BMHDA (24.6 +/- 11.5%). At 20 min, 11C-activity in lipid was distributed primarily between triglyceride (47 +/- 16% of total) and phospholipid (39 +/- 17%) pools. Partial oxidation to 11CO2 and partitioning into more than one lipid pool are likely to hinder evaluation of fatty acid metabolism based on residue detection of [1-11C]BMHDA with tomography.

Animals↗

PubMed1987

Substrate use in ischemic and reperfused canine myocardium: quantitative considerations.

The patterns of use of substrate in reperfused myocardium are not yet well elucidated, and their delineation is essential for adequate interpretation of results of analyses performed after positron emission tomography with labeled substrates to differentiate normal from abnormal heart muscle. Accordingly, in open-chest, anesthetized dogs we measured glucose and fatty acid utilization in normal, ischemic, and reperfused myocardium and assessed the contributions of metabolism of each substrate to overall oxidative metabolism. Intracoronary [3H]glucose and [14C]palmitate were administered in five control dogs, eight dogs subjected to 1 h of coronary occlusion, and nine dogs subjected to reperfusion after 1 h of ischemia. Regional coronary venous blood samples were assayed sequentially. In reperfused myocardium, utilization of glucose (463 +/- 88 nmol X g-1 X min-1) was 103% greater than that in ischemic and 273% greater than in normal myocardium (P less than 0.05 for each). Utilization of fatty acid during reperfusion (55 +/- 10 nmol X g-1 X min-1), although greater than that in ischemic myocardium, was significantly less than that in normal myocardium (48% of control, P less than 0.05) despite restoration of flow to 80% of control values. Although glucose constituted 70% of the substrate oxidized in ischemic myocardium, its contribution to overall oxidative metabolism in reperfused myocardium was only 25%. In contrast, despite diminished net uptake of fatty acid, oxidation of fatty acid accounted for 63% of total oxygen consumption in reperfused myocardium. These studies indicate that canine myocardium reperfused after 1 h of ischemia exhibits enhanced uptake of glucose and impaired utilization of palmitate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes.

To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 (111In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed (p less than .01). In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures.

Animals↗

PubMed1987

Delineation of myocardial oxygen utilization with carbon-11-labeled acetate.

Although positron-emission tomography (PET) with labeled fatty acid delineates infarct size and permits qualitative assessment of fatty acid utilization, quantification of oxidative metabolism is limited by complex alterations in the pattern of utilization of fatty acid during ischemia and reperfusion. Because metabolism of acetate by myocardium is less complex than that of glucose or palmitate, we characterized kinetics of utilization of radiolabeled acetate in 37 isolated rabbit hearts perfused with modified Krebs-Henseleit buffer and performed a pilot tomographic study in man. Results of initial experiments with carbon-14-labeled acetate (14C-acetate) indicated that the steady-state extraction fraction of acetate averaged 61.5 +/- 4.0% in control hearts (n = 4), 93.6 +/- 0.9% in hearts rendered ischemic (n = 4), and 54.8 +/- 4.0% in hearts reperfused after 60 min of ischemia (n = 3). Oxidation of 14C-acetate, assessed from the rate of efflux of 14CO2 in the venous effluent, correlated closely with the rate of oxygen consumption under diverse metabolic conditions (r = .97, p less than .001). In addition, no significant differences were observed between rates of efflux of total 14C in all chemical species (reflecting total clearance of tracer from myocardium) and efflux of 14CO2. Clearance of 11C-acetate, measured externally with gamma probes in normal and ischemic myocardium, correlated closely with clearance of 14C-acetate measured directly in the effluent (r = .99, p less than .001) and with overall myocardial oxygen consumption (r = .95, p less than .001). Accumulation and clearance of 11C-acetate from human myocardium with PET demonstrated kinetics comparable to those seen with radiolabeled acetate in vitro. Thus externally detectable clearance of 11C-acetate provides a quantitative index of myocardial oxidative metabolism despite variation in the patterns of intermediary metabolism that confounds interpretation of results with conventionally used tracers such as glucose and fatty acid.

Acetates↗

PubMed1987

Determinants of salvage of jeopardized myocardium after coronary thrombolysis.

Coronary thrombolysis is an attractive approach for salvaging jeopardized, ischemic myocardium. The advent of second- and third-generation clot-selective thrombolytic agents will make this approach safer and more widely applicable in the future. However, residual stenoses and reocclusion are common after the thrombolytic therapy. In addition to thrombolysis, future management of coronary thrombosis may include adjunctive pharmacologic therapy such as calcium-channel antagonists, beta-blockers, or oxygen free radical scavengers, and/or mechanical interventions such as balloon or laser angioplasty, or bypass surgery.

Angioplasty, Balloon↗

PubMed1987

Coronary thrombolysis with tissue-type plasminogen activator.

Although the value of reperfusion has not yet been convincingly established in humans, initial data with precise end points appear to indicate salutary effects. t-PA will have a clear role in the initial phase of treatment of myocardial infarction, but it must be administered promptly, and residual stenosis must be evaluated and treated if reocclusion is to be prevented. Optimum therapy may involve concomitant pharmacologic agents as well as mechanical or surgical intervention. Long-term goals must address the underlying pathophysiology of coronary atheromata formation and thrombogenesis and primary prevention.

Animals↗

PubMed1987

The temporal pattern of recovery of myocardial perfusion and metabolism delineated by positron emission tomography after coronary thrombolysis.

Recovery of mechanical function by ischemic myocardium is dependent on the restoration of nutritive blood flow and oxidative metabolism subsequent to reperfusion. To characterize the time course and extent of recovery of perfusion and metabolism, we used positron emission tomography with 15O-labeled water and 11C-labeled palmitate to sequentially study six dogs after 2 hr of ischemia followed by reperfusion for 4 wk. Myocardial blood flow in the ischemic region increased from 15 +/- 8% of normal during coronary occlusion to 82 +/- 25% 1 hr after reperfusion. Despite maintained coronary patency documented angiographically, flow was reduced after 24 hr to 37 +/- 16% of normal. This decrease was temporary, with flow returning to 66 +/- 11%, 62 +/- 7%, and 64 +/- 18% of normal after 1, 2, and 4 wk of reperfusion, respectively. Uptake of 11C-labeled palmitate paralleled alterations in perfusion during ischemia and early reperfusion, averaging 32 +/- 15% of normal during ischemia, and 67 +/- 22% and 36 +/- 10% after 1 and 24 hr of reperfusion. After that, palmitate uptake was more variable. Flow and fatty acid uptake after 4 wk of reperfusion were not related to collateral flow during ischemia or the extent of initial reperfusion. However, uptake of palmitate 1 hr after reperfusion was a strong predictor of the uptake of palmitate 4 wk after reperfusion (r = 0.86, p less than 0.03). The results indicate that positron emission tomography with 15O-labeled water and 11C-labeled palmitate may be useful for assessing the success of recanalization in restoring nutritive perfusion and fatty acid metabolism and that the uptake of [11C]palmitate early after reperfusion predicts the ultimate salvage of myocardium.

Animals↗

PubMed1987

Metabolic fate of radiolabeled palmitate in ischemic canine myocardium: implications for positron emission tomography.

Interpretation of dynamic and integrated myocardial tomograms requires elucidation of the biochemical fate of the tracer and characterization of its tissue distribution and rate of efflux. The fate of [1-11C] and [1-14C]palmitate was studied in 13 open-chest dogs during control or ischemic extracorporeal perfusion of the left circumflex coronary artery. Residue detection of myocardial radioactivity, and radio-biochemical analyses of sequential transmural biopsies and arterial and coronary venous effluent were performed for 30 min after intracoronary bolus administration of tracer. In control hearts, 10.3% of initially extracted tracer was retained in tissue (2.9% in triglyceride, 3.5% in phospholipid, and 3.9% in other lipid and aqueous fractions), 73.7% was oxidized, and 16.1% back-diffused unaltered. With ischemia (pump flow 10% of normal), 28.1% was retained (18% in triglyceride, 6.0% in phospholipid, and 4.1% in other lipid and aqueous fractions), 27.2% was oxidized, and 44.4% back diffused (p less than 0.05 compared to control). Throughout the 30-min study interval, triglyceride, diglyceride, and nonesterified fatty acid comprised a significantly greater fraction of initially extracted radioactivity in ischemic than in control hearts. Thus, during ischemia externally detected clearance rates cannot be used as a direct measure of fatty acid metabolism because of marked influences on efflux of nonmetabolized radiolabeled palmitate and the distribution of tracer retained in tissue. Quantitative measurements of specific metabolic processes by tomography will require development and validation of tracers confined to individual metabolic pathways or pools.

Animals↗

PubMed1986

External detection of beta-adrenoreceptors with 125I-hydroxybenzylpindolol in isolated perfused hearts.

To assess the feasibility of characterizing beta-adrenoreceptors externally with ligands labeled with gamma-emitting radionuclides, we infused 125I-hydroxybenzylpindolol (125I-HYP) a potent, high affinity, beta-adrenoreceptor ligand into isolated perfused hearts and monitored uptake and release of the label externally with a gamma probe. Perfusion with specific beta-adrenergic displacing significantly increased the turnover rate constant of 125I-HYP in comparison to that obtained with non-specific displacing agents. After modifying beta-adrenoreceptor density by pretreatment of animals with thyroid hormone, an increase in 125I-HYP uptake was observed. Thus, beta-adrenoreceptor occupancy and increases in beta-adrenoreceptor density can be detected externally with an approach which may offer promise for their characterization in vivo with radiolabeled adrenergic ligands.

Animals↗