Biomedical subjects
E Carlsson
Publications and source records attributed to E Carlsson.
beta 1-and beta 2-adrenoceptor stimulatory effects of prenalterol.
Prenalterol, previously characterized as a functionally cardioselective partial beta-adrenoceptor agonist, was shown to relax K+ -elicited contractures in the uterine muscle from progesterone pretreated rats (pD2 7.7) and to increase beating rate in the rat right atrium (pD2 8.0) at about the same concentrations with maximal effects corresponding to 94 and 82% respectively of those of isoproterenol. Terbutaline, with equal maximal effects as isoproterenol, was 50 times more potent in the uterus (pD2 7.8) than in the right atrium (pD2 6.1). Both tissues displayed a high sensitivity to isoproterenol (pD2 9.1 in both tissues) indicating large receptor reserves for the full agonist. The maximal relaxing effect of prenalterol in the uterus was obtained at about a three-fold increase of the cyclic AMP content, which is similar to that obtained with isoproterenol at a corresponding relaxation. The effects in the uterine muscle of all three agonists were mediated through beta 2-adrenoceptors since beta 2-adrenoceptor blockers (ICI 118, 551 and IPS 339) antagonized the effects in concentrations which had only marginal effects on the atrial responses of the agonists. The beta 1-antagonists pafenolol and pamatolol in concentrations higher than those, which blocked the effects of the agonists on beating rate, were devoid of inhibitory effects in the uterus. These results indicate that prenalterol possesses the ability to elicit a functional response by stimulation of either beta 1-or beta 2-adrenoceptors provided that the tissue has a large spare receptor reserve for full agonists.
Cardiostimulatory effects of prenalterol, a beta-1 adrenoceptor partial agonist, in vivo and in vitro. Correlation between physiological effects and adenylate cyclase activity.
The cardiostimulatory effects of prenalterol, a beta-1-adrenoceptor partial agonist, were studied in vivo and in vitro and compared to those evoked by isoprenaline, a full agonist, and to those of other partial agonists. In the anaesthetized rat, prenalterol and terbutaline were found not to elevate the myocardial cyclic AMP content; this was in sharp contrast to isoprenaline. Both partial agonists did, however, produce significant effects on heart rate. In the anaesthetized cat, prenalterol exhibited chronotropic and inotropic intrinsic activities of 88 and 76% respectively in relation to isoprenaline. No statistically significant increase in myocardial cyclic AMP content could however be detected. Prenalterol did not stimulate adenylate cyclase significantly in the cat myocardial homogenate. This was also true of the beta-2-adrenoceptor selective partial agonist procaterol. In this preparation, isoprenaline, noradrenaline and adrenaline acted as full agonists. Furthermore, prenalterol produced a concentration-dependent inhibition of isoprenaline-activated adenylate cyclase. Our data indicate that maximal cardiac stimulation occurs at a low level of adenylate cyclase activation and low myocardial cyclic AMP concentration when provoked by a full beta-adrenoceptor agonist. The maximal physiological effects of a partial agonist such as prenalterol may consequently be achieved at a marginal activation of the adenylate cyclase. The present data may thus support the hypothesis of a large beta-adrenoceptor reserve for full agonists in the heart.
Computer graphic display of cardiac CT scans.
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Washout curves from myocardial infarctions in dogs, studied by contrast-enhanced computed tomography.
Experimental myocardial infarctions appear on CT scans as areas of mixed high and low densities. As the healing of the infarction proceeds, the low-density areas gradually decrease in size and disappear completely within 5 weeks. Healed infarctions appear as a high-density area only. In order to explore the contrast medium transport in the infarcted area, washout curves were constructed from the infarct components, the normal myocardium, and the left ventricular cavity at regular intervals over a period of 145 days. All regions except the low-density zones showed continuous decrease in density during the washout. The low-density zones showed gain in density during the first 10 to 15 min of washout, probably representing slow diffusion of contrast medium into the necrotic tissue. During the first 5 weeks of the healing process, the washout curve from the low-density zones gradually became similar and ultimately conformed to the other curves, concomitant with the ongoing neovascularization of the lesion.
Ultrastructural identification of human fetal Purkinje fibres--a comparative immunocytochemical and electron microscopic study of composition and structure of myofibrillar M-regions.
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Basic pharmacological properties of prenalterol.
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The haemodynamic effects of intravenous prenalterol and ouabain in conscious dogs.
Experiments were performed on 5 resting conscious dogs supplied with an electromagnetic flow probe on the ascending aorta and a chronic aortic catheter for pressure recording. The animals were used repeatedly in four different types of experiment involving i.v. administration of 1. saline (controls), 2. prenalterol 45 nmol/kg (approximately 10 micrograms/kg) followed by an additional dose of 135 nmol/kg 20 min later, 3. ouabain 50 nmol/kg (approximately 30 micrograms/kg) and 4. a combination of protocols 2. and 3. Ouabain and the low dose of prenalterol exerted clear-cut positive inotropic effects as reflected in increased stroke volume and max dF/dt without significant changes in heart rate or arterial pressure. The PQ interval increased with ouabain but decreased with prenalterol. The higher dose of prenalterol caused a further rise in max dF/dt, a further shortening of the PQ time, increased heart rate and reduction in systemic vascular resistance. Higher doses of ouabain could not be given due to side-effects (vomiting). The combined treatment with ouabain and prenalterol showed their inotropic responses to be additive. Arrhythmias did not occur in any of the animals at the applied dose levels of the drugs. The experiments show that prenalterol through its beta 1-adrenoceptor stimulating action exerts a positive inotropic effect which surpasses that of emetic doses of ouabain. The inotropic response at moderate doses occurs without a change in heart rate. This fact and the apparent lack of influence of prenalterol on vascular alpha- and beta 2-adrenoceptors make the substance potentially useful clinically as an inotropic agent in cardiac failure, particularly in view of its relatively long duration of action.
Differentiation of the myofibrils and the intermediate filament system during postnatal development of the rat heart.
The differentiation of the myofibrils and the intermediate filament system during postnatal development of the rat heart has been investigated. Several aspects of some of the structural proteins, that means the intermediate filament subunit skeletin, myosin, and the myofibrillar M-line proteins MM-creatine kinase and myomesin have been studied by using gel electrophoresis as well as enzyme and immunohistochemical techniques in combination with electron microscopy of both plastic and cryosectional material. We show that marked changes take place in the organization of the intermediate filament system and in the contractile apparatus, both in atria and in ventricles of the rat heart during postnatal development. In the newborn rats no dense myofibrillar M-bands were present in the M-region and the sarcomeric bands were irregular while in the four-week-old rats dense M-bands composed of a set of five crossbridges interconnecting the thick filaments were present. The sarcomeric bands were now regular. These observations are related to the presence of different isomyosins in the atria and in the ventricles of the newborn and the four-week-old rats, to the observation that MM-creatine kinase was only present in the M-region in the four-week old rats and to the physiological maturation of the heart.
[Adult orthodontics. A literature study].
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Technical aspects and clinical applications of CT/X, a dynamic CT scanner.
CT/X is an X-ray computed tomographic scanner system designed for research in the clinical applications of rapid sequence scanning. The minimum scan time is 1.5 sec, and up to 18 images of the same cross section can be derived from scans taken over a 30 sec time interval. With this high image rate, the transit of a bolus of iodinated contrast medium can be followed through any cross section of the body. Rapid sequence scanning through a series of contiguous levels can also be performed, and 12 levels can be scanned in less than 50 sec. The short aggregate scan period minimizes the likelihood of interslice patient motion resulting in high quality multiplanar images. To fully exploit this capability, an imaging facility capable of reformatting axial transverse display data into a plane of arbitrary orientation has been incorporated into the system. A computer-electrocardiographic interface is also provided for use in retrospective cardiac gating. The capabilities of the scanner are illustrated with selective clinical studies.
Recurrent abdominal pains as the first symptom of a spinal cord tumor.
Recurrent abdominal pains occur in about 11% of children. Of these about 8% have an organic etiology. That a spinal cord tumor, especially the intramedullary type, may present with abdominal pains as the initial symptom is unknown in paediatric circles. To highlight this problem two patients are reported. Early diagnosis is essential. The most important clues to a spinal cord tumor are pain, progressive paralysis, and a sensory level. In children with recurrent abdominal pains of unclear etiology the possibility of a spinal cord tumor must be kept in mind and lead to appropriate investigations.
Detection and quantitation of myocardial infarction in vivo using transmission computed tomography.
In vivo studies were performed on 28 dogs to evaluate the usefulness of transmission computed tomography (CT) in the detection and quantitation of experimentally induced myocardial infarction. Intravenously administered contrast material was required to define the internal structure of the heart and to differentiate normal from infarcted tissue. Transmural infarcts with homogeneous central regions were visualized as areas of diminished contrast enhancement compared with the normal myocardium. All transmural infarcts of at least 24 hours' duration showed a surrounding border zone of patchy necrosis that was variable in size and had high CT numbers due to slow washout of the contrast material from this region. Infarct area determined from the images for individual slices correlated well (r = 0.976) with that calculated using pathology. The technique is very sensitive and can detect infarction within a papillary muscle. Nontransmural or patchy infarcts show up as areas of diffuse contrast enhancement without a central core of diminished enhancement. The distribution of the contrast material is similar to that of technetium-99m pyrophosphate in the border zone of the infarct in infusion studies, but in bolus studies it behaves more like thallium-201.
Ventricular diastolic pressure-volume relations and the pericardium. Effects of changes in blood volume and pericardial effusion in dogs.
We investigated the role of the pericardium in the mechanism of shifts in the left ventricular (LV) diastolic pressure-volume relation produced by changes in circulating blood volume and by pericardial effusion. Twelve closed-chest anesthetized dogs were instrumented with pericardial and pleural balloons and intracardiac catheters for pressure measurements. We measured the volumes of the pericardium and the left and right ventricles by computed tomography (CT), integrating the area of CT cross-sections measured at 1-cm intervals from the cardiac apex to the aortic arch. The volumes of the pericardium and the cardiac chambers were changed by infusing 40 and 80 ml of dilute contrast medium into the pericardial space, by bleeding, and by rapidly infusing saline intravenously. Pericardial effusions of 80 ml reduced mean right ventricular volumes to 59% of control, whereas LV volumes were less severely compromised (81% of control). Total pericardial volume and pressure increased. Intravenous saline infusions, which raised right atrial pressure 10-15 mm Hg, produced increases of this magnitude in pericardial pressure. This was also the magnitude of the upward displacement in the LV diastolic pressure-volume relation after infusion. However, LV diastolic transmural pressure-volume coordinates fell along a single curve. Similar behavior was observed for the right ventricular diastolic pressure-volume relation. Pericardial transmural pressure-volume curves were described. When cardiac volume was altered by volume load and pericardial effusion, acute shifts in the LV diastolic pressure-volume relation were caused by changes in pericardial pressure, which, in turn, corresponded to changes in pericardial volume.
Myocardial infarction in dogs, demonstrated by non-enhanced computed tomography.
The capability of non-enhanced and enhanced CT scanning of the heart without ECG gating to detect myocardial infarction in living dogs was explored. CT findings were correlated with those at post mortem. In large transmural infarctions, areas of lower attenuation were detected without contrast medium enhancement and appeared as defects when intravenous contrast medium was administered. The infarct size as estimated on each CT scan correlated closely with post mortem values.
Validation of geometric methods for estimating segmental myocardial motion of the left ventricle at cineangiography.
Functional myocardial changes which result from ischemia are typically local rather than total. For assessing such regional changes quantitatively, left ventricular angiography has been used. The ventricular image has been divided into several components which can be measured individually. In order to test the validity of such methods, left ventricles of 5 dogs were labeled with endocardial tantalum markers and the segmental myocardial motion was estimated using cineangiography. Variance analysis of beat to beat measurements of total ejection fractions was performed. Total ejection fraction demonstrated the least variation with an average 3.5 per cent, segmental myocardial shortening 15 and regional stroke volumes 13 to 18 per cent. Intermethodologic variation with different regional volume measurements was 11 to 13 per cent. Regional stroke volume calculations showed large methodologic variations in beat to beat analysis. Conclusions and clinical decisions based on such measurements should be drawn with caution.
Repair of dissection of the thoracic aorta. Evaluation of false lumen utilizing computed tomography.
During the period 1975 to 1980, 21 patients with thoracic aortic dissections underwent surgical treatment. The operative technique was resection and tube graft replacement of the segment of the aorta containing the entry point into the false channel. Eleven Type A and 10 Type B dissections were resected. The hospital survival rate was 95%. The single operative death occurred in a patient with an acute Type A dissection. Three patients had total resection of the dissected segment; three had clotted false lumina; five had distal anastomosis to true and false lamina; and 10 had distal anastomosis to the true lumen only, with proximal entry into the false lumen obliterated by incorporating both intimal and adventitial walls in a single suture line. The late survival rate was 95% (mean 32 months, range 8 to 63 months). No late ruptures occurred. Computed tomography (CT) with contrast enhancement was used to evaluate the aorta and any residual false lumen at follow-up. Seven of eight patients in whom obliteration was attempted and CT scans performed demonstrated persistence of false lumen perfusion; in six of the eight, preoperative angiograms were adequate for evaluation of false lumen runoff. Major vessels arose from the false lumen in all cases, except in the one patient in whom obliteration was later successful. This report demonstrates that there is persistence of false lumen perfusion in patients in whom obliteration is attempted, and the mechanism of this persistence is the presence of major vessel runoff. It suggests that the mechanism by which long-term survival is achieved is by resection of the segment of aorta containing the entry site, which is frequently the site of subsequent enlargement and rupture, rather than obliteration of the false channel.
Prenalterol, a non-selective beta-adrenoceptor ligand with absolute beta1-selective partial agonist activity.
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