Search PubMed⌕ Search

Biomedical subjects

S R Bergmann

Publications and source records attributed to S R Bergmann.

At least 127 records · Page 7Linked to original sources

Noninvasive detection of coronary thrombi with In-111 platelets: concise communication.

The need for rapid, definitive identification of coronary thrombosis has been intensified by the advent of thrombolytic therapy and by interest in the role of thrombosis in the etiology of coronary artery disease. To determine whether platelet thrombi can be detected noninvasively with In-111 platelets, a method was developed in which Tc-99m-tagged red blood cells were used to correct for activity within the blood attributable to platelets circulating but not associated with thrombus. In 18 dogs coronary thrombi were induced closed-chest with a copper coil introduced into the coronary artery. Indium-111 platelets and Tc-99m RBCs were administered either before or 1 hr after induction of thrombus, and serial scintigrams obtained. Coronary thrombus was identified readily in the processed scintigrams. In six dogs, thrombolysis was achieved with intracoronary streptokinase. In each case serial scintigraphy demonstrated resolution of the clot. The dual radiotracer technique should permit serial noninvasive delineation of the temporal relationship between platelet deposition and coronary heart disease in patients, and should facilitate the evaluation of interventions designed to prevent platelet aggregation or to lyse existing thrombi.

Animals↗

Temporal dependence of beneficial effects of coronary thrombolysis characterized by positron tomography.

To delineate beneficial effects of intracoronary thrombolysis on myocardial metabolism in vivo and their dependence on the interval after coronary occlusion prior to reperfusion, we studied 23 closed-chest dogs. Coronary occlusion was produced with a thrombogenic copper coil to performance of cardiac positron emission tomography with 11C-palmitate. Jeopardized zones were calculated by summation by myocardial regions exhibiting less than 50 percent of the peak left ventricular wall radioactivity, and residual metabolic activity within jeopardized zones quantified based on the average counts compared with average counts in normal myocardium. After tomography, streptokinase was infused into the coronary artery (4,000 units per minute), resulting in angiographically demonstrable restoration of patency. Repeat tomography performed 90 minutes after the initial study with a second injection of 11C-palmitate demonstrated reduction of jeopardized zones by 51 +/- 6.3 percent (SE) and by 21 +/- 1.8 (p less than 0.01 based on paired comparisons) when refusion was initiated 1 to 2 (in four dogs) or 2 to 4 (in six dogs) hours after occlusion. Metabolic activity in initially jeopardized regions increased by 111 +/- 24.3 percent and 61.8 +/- 12.6 (p less than 0.01 for each). When streptokinase was infused later after occlusion, significant salutary metabolic effects did not occur. These results indicate that positron tomography may be useful in the clinical delineation of the efficacy of thrombolytic therapy in restoring myocardial metabolism and underscore the marked dependence of such efficacy on the duration of the interval of ischemia prior to the onset of reperfusion.

Animals↗

Influence of cardiac and respiratory motion on tomographic reconstructions of the heart: implications for quantitative nuclear cardiology.

The potential influence of physiological, periodic motions of the heart due to the cardiac cycle, the respiratory cycle, or both on quantitative image reconstruction by positron emission tomography (PET) has been largely neglected. To define their quantitative impact, cardiac PET was performed in 6 dogs after injection of 11C-palmitate under disparate conditions including: normal cardiac and respiration cycles and cardiac arrest with and without respiration. Although in vitro assay of myocardial samples demonstrated that palmitate uptake was homogeneous (coefficient of variation = 10.1%), analysis of the reconstructed images demonstrated significant heterogeneity of apparent cardiac distribution of radioactivity due to both intrinsic cardiac and respiratory motion. Image degradation due to respiratory motion was demonstrated in a healthy human volunteer as well, in whom cardiac tomography was performed with Super PETT I during breath-holding and during normal breathing. The results indicate that quantitatively significant degradation of reconstructions of true tracer distribution occurs in cardiac PET due to both intrinsic cardiac and respiratory induced motion of the heart. They suggest that avoidance of or minimization of these influences can be accomplished by gating with respect to both the cardiac cycle and respiration or by employing brief scan times during breath-holding.

Animals↗

Kinetics of positron emitters in vivo characterized with a beta probe.

To facilitate characterization of regional myocardial kinetics of positron-emitting tracers in vivo without distortion by activity outside the region of interest, a probe was developed and evaluated for monitoring radioactivity by detection of positrons themselves. These particles (beta particles) have a maximal range in tissue of only few millimeters rather than the larger range of gamma photons emitted as a result of positron annihiliation. Regional myocardial time-activity curves were determined in open-chest dogs after intracoronary injection of 0.5-1.5 mCi [15O]H2O, a tracer used for measurement of myocardial blood flow, or 6.0-8.0 mCi [11C]palmitate, a tracer used for noninvasive assessment of myocardial metabolism. Time-activity curves after [11C]palmitate injection clearly delineated specific components of myocardial tracer clearance previously identified in vitro in isolated perfused hearts. Myocardial washout of [15O]H2O was monoexponential for more than 2 min without distortion induced by recirculating tracer in ventricular blood. Reproducibility of measured tracer clearance rates during monoexponential clearance was high based on duplicate determinations for both tracers. The beta-detector probe developed overcomes several intrinsic limitations of gamma-probe systems or well counting of serial myocardial biopsies for studies of positron-emitting tracers in vivo and should facilitate assessment of factors of influencing tracer kinetics in vivo relevant to positron-emission tomography.

Animals↗

Detection of cardiac transplant rejection with radiolabeled lymphocytes.

To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy.

Animals↗

Monitoring of cardiac antirejection therapy with In-111 lymphocytes.

To determine whether lymphocytes labeled with indium-111 permit noninvasive assessment of antirejection therapy, we performed 40 allogeneic heterotopic cardiac transplants in rats. Antirejection therapy with azathioprine (30 mg/kg) and sodium salicylate (200 mg/kg) prolonged contractile function of the graft from 7.5 +/- 1.5 (s.d.) days in controls to 19.4 +/- 3.7 days in treated animals. Six to seven days after transplantation, autologous lymphocytes labeled with In-111 were injected intravenously in seven untreated and eight treated rats. Scintigraphy and organ counting were performed 24 hr after administration of labeled cells. At sacrifice all grafts in untreated rats exhibited contractile failure, whereas grafts in all treated rats were beating well. Transplants in untreated recipients exhibited marked accumulation of In-111 lymphocytes detectable scintigraphically, with ratios of 7.7 +/- 1.9 for the activity in the transplant over that in the native heart (HT/HO), as obtained by well counting. In contrast, accumulation was not scintigraphically detectable in transplants of treated rats, with HT/HO ratios of 2.6 +/- 1.8 (p less than 0.005). The results suggested that imaging with in-111-labeled lymphocytes will permit noninvasive assessment of antirejection therapy.

Animals↗

Identification of fatty acid ethyl esters as products of rabbit myocardial ethanol metabolism.

To characterize metabolic factors potentially associated with alcohol-induced heart disease, myocardial ethanol intermediary metabolism was studied in isolated, perfused rabbit hearts and whole heart homogenates. Results showed that intact rabbit hearts and homogenates of rabbit left ventricle incorporate carbon-14-labeled ethanol at 20 and 59 nmol/g/h, respectively, into a neutral lipid species that co-migrates with triacylglycerides in standard chromatographic solvent systems. After isolation and purification by thin layer chromatography in an apolar solvent system, the labeled species were identified by gas chromatographic-mass spectral analysis to be a family of fatty acid ethyl esters. Heat inactivation of incorporation and the kinetics of formation of products suggest that the process is enzymatic. Gas chromatography identified the fatty acid components as predominantly unsaturated moieties, especially oleic, linoleic, and arachidonic acids. These results provide insight into potential biochemical mechanisms contributing to the triacylglyceride accumulation, decreased beta oxidation of fatty acids, and other lipid abnormalities typical of effects of ethanol on the heart.

Animals↗

Effects of amphiphiles on erythrocytes, coronary arteries, and perfused hearts.

Due to their unique structure, lysophosphoglycerides (such as lysophosphatidylcholine, LPC), compounds known to accumulate in ischemic myocardium, form micelles at concentrations exceeding the critical micelle concentration (CMC). In this study, we found that sub-CMC levels of LPC exerted dose-dependent morphological changes on red blood cells and elicited dysrhythmia and contracture while increasing coronary artery resistance in isolated hearts. LPC at supra-CMC concentrations lysed red blood cells, elicited virtually instantaneous contracture in perfused hearts, and constricted isolated coronary arteries. Because bile salts form micelles also, effects of LPC were compared with those induced by selected concentrations of bile salts. At sub-CMC levels, bile salts did not affect red cell morphology appreciably and exerted only negative ino- and chronotropic effects in isolated hearts. However, at supra-CMC concentrations, bile salts lysed red blood cells and caused contracture in the hearts. Thus LPC exerts specific effects at sub-CMC levels independent of nonspecific detergent effects of micelles. These specific effects may contribute to the mechanical and electrical dysfunction associated with myocardial ischemia.

Animals↗

An improved assay with 4-(2-thiazolylazo)-resorcinol for non-esterified fatty acids in biological fluids.

A simple and rapid colorimetric assay for non-esterified fatty acids (NEFA) was developed employing extraction of samples with 0.1 mol/l glycine (pH 2.7) and methoxyethanol : butyl ether, and formation of a copper-fatty acid soap detected with 4-(2-thiazolylazo)-resorcinol. The method developed is sensitive enough to detect as little as 11 nmol/0.25 ml sample. Results are not affected by marked molar excesses of phospholipids, cholesterol, cholesterol esters, triglycerides, bilirubin, or lactate. Recovery of palmitate in the extract averages 94.2 +/- 3.2% (S.D.) and other long chain fatty acids are recovered equally. The copper-NEFA-indicator complex formed is stable. Extracted samples can be stored for as long as 2 weeks without appreciable changes in measured NEFA content. The method developed is suitable for both manual and semi-automated procedures for determining NEFA content in biological fluids.

Animals↗

External quantification of myocardial perfusion by exponential infusion of positron-emitting radionuclides.

A technique was developed and evaluated using the exponential infusion of positron-emitting diffusible tracers to quantitate myocardial perfusion. The approach employs a parameter that rapidly reaches a constant value as a function of tracer delivery rate, isotope decay constant, and the monotonically increasing tissue radioactivity. Isolated rabbit hearts with controlled flow were used to evaluate the approach, because tracer kinetics in such preparations mimic those in vivo. Accordingly, exponential infusions of H2 15O and [11C]butanol were administered to 25 isolated rabbit hearts perfused with Krebs-Henseleit solution (KH) alone or KH enriched with erythrocytes (KH-RBC, hematocrit = 40). With flow varied from 1.2 to 5 ml/g per min in eight KH hearts infused with H2 15O, actual and estimated flow correlated closely (r = 0.95, n = 52 determinations). For the KH-RBC hearts, flow was varied from 0.3 to 1.5 ml/g per min. Actual and estimated flow correlated significantly for both the 14 KH-RBC hearts infused with H2 15O (r = 0.90, n = 89 determinations) and the 3 KH-RBC hearts infused with [11C]butanol (r = 0.93, n = 13 determinations). In addition, the required exponentially increasing arterial tracer concentrations were shown to be attainable in vivo in dogs and rhesus monkeys after intravenous exponential administrations of tracer. The results suggest that the approach developed employing exponential tracer infusion permits accurate measurement of myocardial perfusion and that it should prove useful in the noninvasive measurement of regional myocardial perfusion in vivo by positron emission tomography.

Animals↗

An improved isolated heart preparation for external assessment of myocardial metabolism.

To facilitate characterization of myocardial metabolism with the use of positron-emitting tracers, we developed an isolated heart preparation designed to simulate physiological levels of flow and substrate extraction. Isovolumically beating hearts were perfused retrograde at 60 mmHg with modified non-recirculating Krebs-Henseleit (KH) solution with or without washed sheep red blood cells at a hematocrit of 25 or 40 (KH-RBC25, KH-RBC40). Left ventricular (LV) systolic pressure averaged 63 mmHg with KH alone, 78 with KH-RBC25, and 98 with KH-RBC40. LV dP/dt, pressure-time index, and oxygen consumption increased in an analogous fashion. Fatty acid extraction increased from 1.5% with KH to 11.8% in hearts perfused with KH-RBC40, although net uptake was not increased markedly because of the associated differences in flow (4.6 ml.g-1.min-1 with KH and 1.5 with KH-RBC40). Hearts perfused with erythrocyte-rich media exhibited functional and metabolic stability and less edema. The preparation avoids intrinsic limitations encountered with buffer-perfused hearts and should prove useful for characterization of cardiac metabolism with radiolabeled tracers relevant to positron emission transaxial tomography.

Animals↗