Right ventricular ischaemia due to right coronary artery stenosis.
Explore the source record for details and available documents.
Coronary Angiography↗
Biomedical subjects
G A Somsen
Publications and source records attributed to G A Somsen.
Neovascularity related to mural thrombus in endomyocardial fibrosis.
We report a 30-year old, previously healthy, Ghanese woman admitted with sudden onset of dyspnoe, hemoptoe and right-sided chest pain due to endomyocardial fibrosis with secondary pulmonary emboli Coronary angiography revealed a myocardial "blush". This finding may focus attention to the presence of mural thrombus that may have diagnostic and therapeutic consequences.
Adult↗
Acute renal failure due to self-medication.
A patient with rhabdomyolysis and transient renal failure due to auto injection of the procaine containing drug "Gerovital" is described. This case illustrates the hazards of self-regulated alternative treatment.
Acute Kidney Injury↗
Comparison between iodine 123 metaiodobenzylguanidine scintigraphy and heart rate variability for the assessment of cardiac sympathetic activity in mild to moderate heart failure.
This study demonstrates that in patients with mild to moderate heart failure, cardiac metaiodobenzylguanidine (MIBG) washout positively correlates with normalized low-frequency power in the heart rate variability spectrum. Alterations of the cardiac sympathetic nervous system could be detected with MIBG scintigraphy in patients with normal plasma norepinephrine levels. Therefore cardiac MIBG washout may be a valuable noninvasive technique to assess early alterations in cardiac sympathetic activity that may have potential clinical implications in patients with mild to moderate heart failure.
3-Iodobenzylguanidine↗
Development of radioligands for the imaging of cardiac beta-adrenoceptors using SPECT. Part II: Pharmacological characterization in vitro and in vivo of new 123I-labeled beta-adrenoceptor antagonists.
Cardiac beta-adrenoceptors are assumed to play a key role in chronic heart failure. Although several radioligands labeled with 11C or 18F have been synthesized for imaging purposes with positron emission tomography (PET), so far no optimal ligands are available to image cardiac beta-adrenoceptors using single photon emission tomography (SPECT). In the present study, we characterized four new synthesized analogues of the nonselective beta-adrenoceptor antagonist 4-(3-t-butylamino-2-hydroxypropoxy)-benzimidazol-2-one (CGP12177) and one analogue of the nonselective beta-adrenoceptor antagonist penbutolol. Using classical in vitro displacement studies with left ventricular tissue of New Zealand White rabbits and [125I]iodocyanopindolol as a radioligand, binding affinity to the receptor was determined. From the four analogues, only (2'S,2"E)- [4-(3'-(1",1"-dimethyl-3"-Iodo-2" propenylamino)-2'-hydroxypropoxy)]-benzimidazol-2-one proved to have a high affinity, with Ki = 1.25 +/- 0.09 nM, n = 3. The other analogues showed relatively low affinity, with Ki-values > 1 nM. The analogue of penbutolol ((S)-(-)-[1-(2-Iodophenoxy)]-3'-(tert-butylamino)-2'-propanol) also showed a Ki value of 0.64 +/- 0.26 nM, n = 3. Subsequently, (2'S,2"E)-[4-(3'-(1",1"-dimethyl-3"-Iodo-2" propenylamino)-2'-hydroxypropoxy)]-benzimidazol-2-one and (S)-(-)-[1-(2-Iodophenoxy)]-3'-(tert-butylamino)-2'-propanol were radioactively labeled with 123I to study their biodistribution in New Zealand White rabbits and to determine specific binding. Significant uptake was observed in both lungs and left ventricles. However, both compounds showed high nonspecific binding in vivo because uptake of the radioligand could not be inhibited by preinjection of different (selective- and nonselective-adrenoceptor antagonists and hydrophilic and lipophilic antagonists) antagonists. In conclusion, although two analogues showed reasonable affinity in vitro for the receptor, their binding in vivo proved to be largely nonspecific, suggesting that these two compounds are unsuitable for imaging purposes. However, because marked differences in affinity for the receptor were observed with only little structural changes between compounds, the present results offer future perspectives for the synthesis of a more specific radioligand.
Adrenergic beta-Antagonists↗
Development of radioligands for the imaging of cardiac beta-adrenoceptors using SPECT. Part I: Asymmetric synthesis and structural characterization of five new iodine-containing beta-adrenoceptor antagonist derivatives.
The asymmetric synthesis of a series of iodinated beta-adrenoceptor ligands is described. One ligand, (S)-(-)-[1-(2-iodophenoxy)]-3'-(tert-butylamino)-2'-propanol (CYBL3), is based on the beta-adrenoceptor antagonist penbutolol. The other ligands are N-iodovinyl and N-iodoaryl analogues of the beta-adrenoceptor antagonist CGP12177. These have been synthesized from 2-amino-3-nitrophenol. Furthermore, radioiodinated [123I]CYBL3 and [123I](2'S,2"E)-[4-(3'-(1",1"-dimethyl-3"-iodo-2" propenylamino)-2'-hydroxy propoxy)]-benzimidazol-2-one have been prepared by radiolabelling the corresponding trialkyltin precursors using [123I]-NaI in the presence of hydrogen peroxide.
Adrenergic beta-Antagonists↗
Synthesis and in vitro and in vivo characteristics of an iodinated analogue of the beta-adrenoceptor antagonist carazolol.
A new (radio)iodinated, beta-adrenoceptor ligand, (S)-(-)-4-[3-[(1,1-dimethyl-3-iodo-(2E)-propenyl)-amino]-2- hydroxypropoxy]carbazole (CYBL8E, 1), was prepared. 1 is an iodinated analogue of the high-affinity beta-adrenoceptor antagonist carazolol (2). The asymmetric synthesis was achieved in four steps starting from 4-hydroxycarbazole. The iodine-123-labeled form was obtained by an iododestannylation reaction with [123I]NaI in the presence of H2O2. Using classical in vitro displacement experiments with membrane fractions of cardiac left ventricular muscle, 1 proved to have a high affinity for the receptor (Ki = 0.31 +/- 0.03). Biodistribution studies performed in New Zealand white rabbits demonstrated the specificity of the binding in vivo to the receptor. Uptake of [123I]1 was reduced significantly in both atrial muscle, left ventricular muscle, frontal cortex, cerebellum, and striatum, by the pretreatment of the animals with different beta-adrenoceptor antagonists. In conclusion, 1 is a potent nonselective beta-adrenoceptor antagonist, which binds specifically to the beta-adrenoceptor in vivo, and is therefore a promising radioligand for the imaging of beta-adrenoceptors using single photon emission computerized tomography.
Adrenergic beta-Antagonists↗
Cardiac iodine-123 metaiodobenzylguanidine uptake in animals with diabetes mellitus and/or hypertension.
The aim of the present study was to evaluate the use of the noradrenaline analogue iodine-123 metaiodobenzylguanidine ([123I]MIBG) for the assessment of cardiac sympathetic activity in the presence of diabetes mellitus and/or hypertension in animal models. One model used Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) rendered diabetic at 12 weeks of age by an intravenous injection of streptozotocin (STZ). The other model used lean and obese Zucker rats. In all groups basic haemodynamic values were established and animals received an intravenous injection of 50 microCi [123I]MIBG. Initial myocardial uptake and wash-out rates of [123I]MIBG were measured scintigraphically during 4 h. After sacrifice, plasma noradrenaline and left cardiac ventricular beta-adrenoceptor density was determined. The diabetic state, both in STZ-treated rats (direct induction) and in obese Zucker rats (genetic induction), appeared to induce a lower cardiac density of beta-adrenoceptors, indicative of increased sympathetic activity. Cardiac [123I]MIBG then showed increased wash-outs, thereby confirming enhanced noradrenergic activity. This parallism of results led to the conclusion that [123I]MIBG wash-out measurements could provide an excellent tool to assess cardiac sympathetic activity non-invasively. However, in hypertension (WKY vs SHR), both parameters failed to show parallelism: no changes in beta-adrenoceptor density were found, whereas [123I]MIBG wash-out rate was increased. Thus, either [123I]MIBG washout or beta-adrenoceptor density may not be a reliable parameter under all circumstances to detect changes in the release of noradrenaline. Changes in the initial uptake of [123I]MIBG were observed as well. This may be a good marker for the disappearance of cardiac innervation, but it seems not to be a good parameter for distinguishing between loss of sympathetic innervation and enhanced uptake of noradrenaline in pathological conditions.
3-Iodobenzylguanidine↗
Neuronal dysfunction in heart failure assessed by cardiac 123-iodine metaiodobenzylguanidine scintigraphy.
In patients with chronic heart failure, increased sympathetic activity and cardiac sympathetic neuronal dysfunction are present and have been related to unfavourable clinical outcome. Modification of these alterations with the objective to improve prognosis has become an important aim of pharmacological therapy for these patients. A noninvasive technique to assess sympathetic neuronal function at the cardiac level may be valuable in evaluating newly developed therapeutic strategies. 123-iodine metaiodobenzylguanidine can be used to visualize cardiac sympathetic nerve function and activity. Single photon emission computerized tomographic is preferred to planar scintigraphy since it does not depend on superposition of other anatomical structures and may allow assessment of regional cardiac 123-iodine metaiodobenzylguanidine uptake. Although the quantitation of cardiac uptake in these tomographic images has several limitations, the use of the left ventricular cavity as a reference, calibrated by the 123-iodine activity in a blood sample drawn at the time of acquisition, may have clinical applications, with respect to the evaluation of therapeutical intervention in patients with heart failure.
3-Iodobenzylguanidine↗
Cardiac 123I-MIBG uptake is affected by variable uptake in reference regions: implications for interpretation in clinical studies.
Cardiac 123I-meta-iodobenzyl guanidine (123I-MIBG) uptake, using the mediastinal region as a reference, is a predictor of outcome in heart failure. Constant uptake in a reference region is required when studying the pharmacotherapeutic effects on the integrity of the cardiac adrenergic system. The aim of this study was to verify the assumption of constant uptake in reference regions and their relation to established predictors of clinical outcome. Planar 123I-MIBG images were obtained in 28 patients with heart failure. The left ventricular ejection fraction correlated with the heart-to-mediastinum (H/M) ratio but not with myocardial 123I-MIBG uptake. Plasma noradrenaline correlated with the H/M ratio, the heart-to-lung (H/L) ratio, mediastinal uptake and age, but not with uptake in the myocardium and lung. Age correlated with the H/M ratio, H/L ratio, mediastinal uptake and lung uptake, but not with myocardial uptake. In a regression model, after the inclusion of age, the H/M ratio and mediastinal uptake were not related to noradrenaline. We conclude that changes in the H/M and H/L ratios are predominantly due to confounding changes in mediastinal uptake or lung uptake. In pharmacological intervention studies, myocardial 123I-MIBG uptake should be assessed using single photon emission tomography or positron emission tomography, which do not rely on reference regions in mediastinum or lung.
3-Iodobenzylguanidine↗
Increased myocardial [123I]-metaiodobenzylguanidine uptake after enalapril treatment in patients with chronic heart failure.
OBJECTIVE: To assess non-invasively the effect of enalapril on cardiac sympathetic neuronal uptake function in patients with congestive heart failure, by using [123I]-metaiodobenzylguanidine (MIBG), which is a noradrenaline analogue. Cardiac MIBG uptake was visualised by single photon emission tomography (SPET). In addition, plasma noradrenaline concentration, indicating systemic sympathetic activity, was measured to see whether it was related to cardiac MIBG uptake. DESIGN: Consecutive patients were treated with enalapril and served as their own controls. SETTING: Cardiac unit of a tertiary care centre. PATIENTS: 23 Patients with chronic, mild to moderate, stable congestive heart failure, and a left ventricular ejection fraction less than 40%. Heart failure was caused by ischaemic heart disease or was idiopathic. INTERVENTIONS: Cardiac MIBG SPET was performed and plasma noradrenaline concentration was measured before and after 6 weeks treatment with enalapril. MAIN OUTCOME MEASURES: Cardiac uptake of MIBG was measured by using the left ventricular cavity and a venous blood sample as a reference. RESULTS: Cardiac uptake of MIBG increased significantly after enalapril treatment, indicating improved cardiac neuronal uptake function. Plasma noradrenaline concentration did not decrease significantly. Cardiac MIBG uptake was not related to plasma noradrenaline concentration. CONCLUSIONS: Cardiac MIBG SPET can be used to assess changes in cardiac sympathetic neuronal uptake function caused by pharmacological intervention. Enalapril seemed to improve cardiac sympathetic neuronal uptake function but did not significantly affect plasma noradrenaline concentrations in a group of patients with predominantly moderate heart failure. These results accord with the hypothesis that restoration of cardiac neuronal uptake of noradrenaline is one of the beneficial effects of enalapril in such patients.
3-Iodobenzylguanidine↗
Cardiac sympathetic neuronal function in left ventricular volume and pressure overload.
OBJECTIVES: In heart failure cardiac sympathetic neuronal function and activity appear to be altered. Although these changes are widely accepted, controversy exists concerning the neurohormonal changes occurring in pressure and volume overloaded hearts. The present study in rabbits was performed to assess the effects of mechanical overload on cardiac sympathetic neuronal function and beta-adrenoceptor density, in relation to left ventricular function. METHODS: In nine rabbits the aortic valve was perforated to induce left ventricular volume overload. Pressure overload was induced by suprarenal banding of the aorta abdominalis (group 1). Five animals were sham operated (group 2). Subanalysis of group 1 was performed for non-failing (n = 5) and failing (n = 4) hearts. Heart failure was defined as any reduction in left ventricular fractional shortening 2 weeks after the second operation compared to baseline. RESULTS: In animals with cardiac overload, left ventricular weight was higher compared with the control animals, 7.99 +/- 1.13 vs. 6.16 +/- 0.86 g (P < 0.02). Left ventricular end diastolic diameter increased from 1.35 +/- 0.16 to 1.57 +/- 0.15 cm (P < 0.005) after surgically induced overload. Left ventricular end systolic diameter and fractional shortening did not change significantly. Myocardial noradrenaline (NA) concentration and beta-adrenoceptor density were significantly lower in group 1 than in group 2, 1005 +/- 393 vs. 1643 +/- 109 ng/g (P < 0.02) and 167 +/- 36 vs. 224 +/- 36 fmol/mg protein (P < 0.03), respectively. Myocardial [123I]-MIBG uptake did not significantly differ between group 1 and 2, 2.1 +/- 0.58 vs. 1.8 +/- 0.44 (%ID/g x kg). A significant positive correlation between myocardial NA concentration and beta-adrenoceptor density was found (r = 0.66, P < 0.02). Myocardial NA concentration was inversely related to left ventricular weight (r =-0.75, P < 0.003). CONCLUSION: The present data indicate that in a condition of cardiac volume and pressure overload, sympathetic activity is enhanced as shown by myocardial noradrenaline depletion and beta-adrenoceptor downregulation. In contrast, no cardiac neuronal dysfunction is observed, even in the stage of early heart failure.
3-Iodobenzylguanidine↗
[Heart failure in a Ghanese woman due to endomyocardial fibrosis].
Endomyocardial fibrosis was diagnosed in a 30-year-old Ghanese woman suffering from heart failure and intracardial thrombi. Endomyocardial fibrosis is an endemic disease in tropical countries with a high mortality rate. Since the aetiology of this disease is still unknown, patients can only be treated symptomatically. Endocardial and myocardial damage give rise to reactive fibrosis, subendocardial infarction and thrombus formation, resulting in heart failure and thromboembolic processes.
Adult↗
Quantitation of myocardial iodine-123 MIBG uptake in SPET studies: a new approach using the left ventricular cavity and a blood sample as a reference.
In patients with chronic heart failure increased sympathetic activity is related to unfavourable prognosis. Since myocardial iodine-123 metaiodobenzylguanidine ([123I]MIBG) uptake is related to myocardial noradrenaline content, i.e. cardiac sympathetic activity, measurement of myocardial [123I]MIBG uptake may be of clinical use in determining prognosis or the effect of pharmacological intervention in these patients. The aim of the present study was to evaluate a new method to quantitate myocardial [123I]MIBG uptake with respect to reproducibility and accuracy. Eighteen [123I]MIBG planar and single-photon emission tomographic (SPET) studies of patients with chronic heart failure were evaluated. Myocardial uptake was calculated from the myocardial (MYO) to left ventricular cavity (C) count density ratio and the 123I activity in a blood sample. This was performed employing planar LAO images, a single-slice SPET method using the midventricular myocardial short-axis slice, and finally a multi-slice SPET method analysing semi-automatically drawn volumes of interest (VOIs). The accuracy of the multi-slice SPET method was verified using a cardiac phantom. The planar method was found to be reproducible [intra- and interobserver coefficients of variation (IACV and IRCV) were 0.025 and 0.012 respectively] but the mean MYO/C count density ratio was only 1.31 +/- 0.16 as a consequence of overprojection. For the single-slice SPET method IACV was 0.2 and IRCV was 0.13, representing poor reproducibility. For the multi-slice SPET method IACV was 0.051, IRCV was 0.047 and the mean MYO/C count density ratio was 5.4 +/- 2.42. Accuracy was 81% at a true MYO/C count density ratio of 6 in the phantom. It is concluded that the multi-slice SPET method using the left ventricular cavity VOI and a blood sample as a reference is a reproducible and accurate method for assessing myocardial [123I]MIBG uptake.
3-Iodobenzylguanidine↗
Pharmacologic characterization in vitro and in vivo of iodine 123-labeled derivatives of the beta-adrenoceptor antagonist CGP12177, designed for the imaging of cardiac beta-receptors.
BACKGROUND: Potential new radioligands for the noninvasive imaging of cardiac beta-adrenoceptors with single-photon emission computed tomography were investigated. METHODS AND RESULTS: Two iodinated derivatives of CGP12177 para (S-CYBL2B) and ortho (CYBL2A) substituted CGP12177 and an iodinated form of nadolol (CYBL1) were synthesized. Their affinity was tested in vitro (left ventricular homogenates). The biodistribution of [123I]S-CYBL2B was evaluated in rabbits. Specific binding was assessed by pretreatment of the animals with 0.1 mumol propranolol. The inhibition constant values (in nanomolars, means +/- SEM; n = 3 to 5) were determined at 1.17 +/- 0.42, 28800 +/- 9260, 11.1 +/- 2.1, 53.0 +/- 19.9, and 1790 +/- 700 for CGP12177, CYBL2A, S-CYBL2B, nadolol, and CYBL1. Myocardial uptake of [123I]S-CYBL2B was not inhibited by pretreatment of the animals with propranolol, but uptake by lung tissue could be blocked by propranolol (0.63% +/- 0.09% vs 0.33% +/- 0.02% % injected dose/g x kg; p < 0.05). In isolated right atria, preincubation with S-CYBL2B induced a parallel rightward shift of the concentration-response curve with isoprenaline. CONCLUSIONS: S-CYBL2B shows high affinity for cardiac beta-adrenoceptors, but binding proved nonspecific in vivo, whereas binding in lung tissue was specific. These results suggest that S-CYBL2B is probably not a suitable radioligand for receptor imaging.
Adrenergic beta-Antagonists↗