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Segments of human right atrial appendages preincubated with [3H]noradrenaline and superfused with physiological salt solution containing desipramine and corticosterone were used to examine whether the cardiac sympathetic nerves are endowed with cannabinoid receptors and to further study pharmacological properties of presynaptic imidazoline receptors. The cannabinoid CB1 receptor agonists CP55,940, HU210 and anandamide inhibited evoked [3H]noradrenaline release. The inhibition by CP55,940 and anandamide was abolished by the CB1 receptor antagonists SR141716A (1 µM) and LY320135 (1 µM). Rauwolscine at the imidazoline receptor-blocking concentration of 30 µM abolished the inhibitory effect of CP55,940 and anandamide. After blockade of α2-adrenoceptors with 1 µM rauwolscine, the imidazoline binding site ligand S23230, which is the (-)-enantiomer of the racemic oxazoline derivative S22687, exhibited low potency in inhibiting electrically evoked [3H]noradrenaline release (pIC30%=4.96), whereas the (+)-enantiomer S23229 and the racemate S22687 were ineffective. In the presence of 30 µM rauwolscine, S23230 did not significantly inhibit evoked release. The imidazoline receptor-mediated inhibitory effect of BDF 6143 and aganodine on evoked [3H]noradrenaline release was abolished by 1 µM SR141716A and by 1 µM LY320135. The inhibitory effect of moxonidine on evoked [3H]noradrenaline release, which is exclusively mediated via activation of α2-autoreceptors, was not antagonized by 1 µM SR141716A. In conclusion, inhibitory cannabinoid CB1 receptors are present on the sympathetic axon terminals of human atrial appendages. Presynaptic imidazoline receptors share the property of other receptors in that they can be stereoselectively activated. The cross-antagonism of imidazoline receptor agonists/antagonists with CB1 receptor antagonists/agonists suggests that these receptors may have certain binding domains in common or that they interact with each other in an unknown manner. [ABSTRACT FROM AUTHOR]

Neoplasms are rare cardiac findings of which myxomas comprise about 75%. We report of 15 patients, predominantly female (60%) with a mean age of 58.8 years. Male patients (40%) were 20 years younger on average. 80% of these tumors developed in the left atrium fixed to the atrial septum. In 2 patients the right ventricle and in 1 patient the right atrium was involved. No left ventricular or bilateral tumors were found. Clinical findings showed a great variety of symptoms. Often misdiagnosis was established until echocardiography was performed. Major symptoms were dyspnea (80%), elevated erythrocyte sedimentation rate (73%), arrhythmias (53%), lung edema (47%), embolization (40%) and anemia (40%). Pathological examination and tumor genesis are still in discussion. Several theories are reported in literature: a true thrombus, thrombus organization with malignant potential, true neoplasms as well as a familiar myxoma complex may explain clinical and histological features. Our findings did not confirm only one theory but emphasize different possibilities. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the role of cardiac Troponin I (cTnI) and CK-MB for early prediction of outcome of patients undergoing coronary artery bypass grafting (CABG) surgery., Methods: In 134 consecutive patients undergoing CABG-surgery blood samples were analyzed for cTnI concentration and CK-MB activity. ECG, hemodynamic parameters and the need for inotropic support, were continuously registered. Patients were divided into group A (uneventful course), group B (ischemia by ECG, hemodynamic stability) and group C (ischemia by ECG and IABP)., Results: After removal of X-clamp an increase cTnI and CK-MB was observed in all patients. Five hrs after stop of CPB group A (8.3+/-4.2 microg/L) had lower cTnI values compared to group B (14.8+/-5.3 microg/L) (p=0.035) and C (54+/-22.8 microg/L) (p=0.023). The cut off value was 14.8 microg/L. Sensitivity and specificity (99%/97%) was higher for cTnI than for CK-MB (90%/30%). The positive predictive value of outcome was better for cTnI (86%) than for CK-MB (33%)., Conclusion: CTnI is a specific and sensitive marker for evaluation of perioperative myocardial ischemia (PMI). Additional determination of CK-MB activity does not provide further clinical information. CTnI should be the marker of first choice in CABG surgery.

On the basis of data obtained in rabbits, the imidazoline receptor ligand rilmenidine has been suggested to decrease blood pressure in humans by activating central alpha(2A)-adrenoceptors. A prerequisite for this hypothesis was the unproved assumption that rabbit and human alpha(2A)-adrenoceptors are equally activated by rilmenidine. Because alpha(2A)-adrenoceptors in the brain and on cardiovascular sympathetic nerve terminals are identical, the latter were used as a model for the former to confirm or disprove this assumption. Human atrial appendages and rabbit pulmonary arteries were used to determine the potencies of alpha(2)-adrenoceptor agonists in inhibiting the electrically (2 Hz) evoked [(3)H]norepinephrine release and of antagonists in counteracting the alpha(2)-adrenoceptor-mediated inhibition induced by moxonidine. In the rabbit pulmonary artery, rilmenidine and oxymetazoline are potent full agonists, whereas in the human atrial appendages they are antagonists at the alpha(2)-autoreceptors, sharing this property with rauwolscine, phentolamine, and idazoxan. In contrast, prazosin is ineffective. In addition, a partial nucleotide and amino acid sequence of the rabbit alpha(2A)-adrenoceptor (a region known to substantially influence the pharmacological characteristics of the alpha(2)-adrenoceptor) revealed marked differences between the rabbit and the human alpha(2A)-adrenoceptor. The sympathetic nerves of both the human atrial appendages and rabbit pulmonary artery are endowed with alpha(2A)-autoreceptors, at which, however, both rilmenidine and oxymetazoline exhibit different properties (antagonism and agonism, respectively). The antagonistic property of rilmenidine at human alpha(2A)-adrenoceptors indicates that in contrast to the suggestion based on rabbit data, the hypotensive property of the drug in humans is not due to activation of alpha(2A)-adrenoceptors but other, presumably I(1)-imidazoline receptors, are probably involved.

Background: Harmonic power Doppler imaging (H-PDI) has been introduced into the field of contrast echocardiography as a contrast-specific imaging modality. However, there has been considerable skepticism as to whether H-PDI would be quantifiable, because it depends on the destruction of microbubbles and has more complex signal processing than gray scale imaging. The aim of the present study was to evaluate the relationship between the concentration of microbubbles and the resulting H-PDI signals even under conditions where bubble destruction is most likely. Furthermore, we evaluated whether microbubbles of Levovist freely pass the microcirculation, which is a prerequisite for the assessment of myocardial blood flow., Methods and Results: A strong positive correlation was found between the H-PDI signals and the amount of microbubbles up to the onset of acoustic shadowing (r = 0. 968, P<0.001). Time-intensity curves for H-PDI of air-filled microbubbles were compared with time-concentration curves of indocyanine green (ICG) in both a flow phantom and a working heart setup. The mean transit times (MTTs) through the myocardium of both agents were compared after a bolus injection into the left coronary artery. A close correlation was observed between 1/MTT and flow in both setups (r>0.98, P<0.0001). However, at high flow rates, the MTTs of the microbubbles were slightly, albeit not significantly, faster than those of indocyanine green., Conclusions: We conclude that microbubbles fulfill the prerequisites of free flowing tracers through the myocardium. Furthermore, H-PDI technology allows a reliable assessment of time-concentration curves of air-filled microbubbles up to the onset of acoustic shadowing.

Background and Objective: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated., Patients and Methods: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection., Results: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction., Conclusions: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.

Background and Objective: There is seroepidemiologic and experimental evidence for a link between Chlamydia (C.) pneumoniae and arteriosclerosis. However, the clinical importance and the pathogenic pathways implicated remain unclear. In the present study, we sought to evaluate the presence and the location of C. pneumoniae in coronary atheroma, as well as a potential prevalence with unstable versus stable angina., Patients and Methods: Retrospectively, coronary plaque material of primary lesions from 51 consecutive patients (44 men, 7 women, mean age 59.6 +/- 9.4 years) was examined for the presence of C. pneumoniae by use of immuno-histochemistry and transmission electron microscopy. The findings associated with clinically acute coronary syndrome according to Braunwald's classification (n = 31) were compared to those with stable angina (n = 20) and regarded for potential relations to characteristic intimal features., Results: Immunoreaction for C. pneumoniae was found in 32 of 51 (63%) coronary plaques. Signals (% prevalence of specific intimal features) were present with necrotic areas (40%), sparse cellularity (40%), neo-vascularization (29%), thrombi (20%), ruptured plaque areas (19%), and fields rich in foam cells and calcifications (13%). Intimal hyperplasia and inflammatory infiltrates showed no signals. As the central finding in this report, C. pneumoniae immunoreaction was more frequently (P < 0.001) found in 26 of 31 (84%) lesions associated with unstable angina or acute myocardial infarction, compared to 6 of 20 (30%) lesions with stable angina (P < 0.001). Intact vessels devoid of arteriosclerotic disease, such as mammarial arteries and saphenous veins, were without C. pneumoniae signals (negative controls). Ultrastructurally, chlamydial elementary bodies were found in foam cells and phagocytosing macrophages, also in fragmented extracellular matrix adjacent to apoptotic and necrotic intimal cells., Conclusions: Chlamydiae pneumoniae were detected in 32 of 51 (63%) coronary primary lesions of symptomatic patients. Most importantly, there was a highly significant prevalence of lesions associated with acute coronary syndrome. Predilection sites of C. pneumoniae were areas that revealed small healing activity and (or) propensity to plaque rupture. The present in situ findings indicate a pathogenic role of Chlamydiae pneumoniae in human (coronary) plaque rupture.

Strips of human right atrial appendages were preincubated with [3H]noradrenaline and then superfused with physiological salt solution containing inhibitors of uptake1 and uptake2. Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). Prostaglandin E2 (PGE2) inhibited the electrically evoked tritium overflow; at the highest concentration investigated, tritium overflow was reduced by about 80% and the pIC50% value was 7.14. The effect of PGE2 was not affected by rauwolscine, which, by itself, increased the evoked overflow. Naproxen failed to affect the evoked tritium overflow and its inhibition by PGE2. The inhibitory effect of PGE2 on the electrically evoked tritium overflow was mimicked by prostaglandin E1, the EP1/EP3-receptor agonist sulprostone and the EP2/EP3-receptor agonist misoprostol with the rank order of potency (pEC50%): sulprostone (7.68) > misoprostol (7.10) > PGE1 (6.39). In contrast, PGF2alpha, the IP/EP1-receptor agonist iloprost and the stable thromboxane A2 analogue U46619 (9,11-dideoxy-11alpha,9alpha-epoxy-methanoprostaglandin++ + F2alpha) did not change evoked tritium overflow. PGD2 caused facilitation. These results suggest that the sympathetic nerve fibres innervating human atrial appendages are endowed with presynaptic inhibitory EP3 and facilitatory DP-receptors. The EP3-receptors appear not to be tonically activated and do not interact with the alpha2-autoreceptors.

Purpose: To demonstrate normal postoperative spiral CT and MRI findings and typical complications in patients with aortic repair after Stanford type A aortic dissection., Methods: 24 patients with aortic repair after Stanford type A aortic dissection were followed up by spiral CT and MRI (0.5 Tesla). Presence of persistent dissection, progressive or new dissection, proximal and distal anastomosis, periprosthetic space, supraaortic vessels, thrombosis and dilatation of the true and false lumen were evaluated., Results: The following postoperative complications were seen: three pseudoaneurysms which developed at the proximal anastomoses of the Dacron prosthesis in two cases and at the insertion site of the reimplanted left coronary artery after implantation of a composite graft (Bentall procedure) in one case; one re-dissection; one perforation of the false lumen; periprosthetic flow in one patient after surgical repair of type A dissection by the graft inclusion technique; progressive dilatation of the false lumen in 4 cases; dilatation of the aortic root in a Marfan patient after replacement of the ascending aorta., Conclusion: Precise knowledge of the surgical technique performed is crucial to accurate postoperative imaging evaluation. MRI is the method of choice in the postoperative follow-up of clinically stable patients with aortic dissections.

In view of the potential pathophysiological and therapeutic implications, presynaptic 5-HT auto- and heteroreceptors have been identified and characterized in isolated human tissues and their functional role has been determined. Such investigations have been carried out in different laboratories including that of the authors. Basic evidence for the involvement of inhibitory 5-HT receptors in modulation of 5-HT release in the cerebral cortex was obtained in slices: exogenous 5-HT inhibited 5-HT release in a manner susceptible to blockade by methiothepin, which given alone facilitated 5-HT release, probably by preventing endogenous 5-HT from activating the inhibitory receptors. The latter receptors are located on the 5-HT nerve terminals themselves, since 5-HT (and sumatriptan) also inhibited 5-HT release from cortical synaptosomes. Their pharmacological properties conform to those of the 5-HT1D class. Subclassification (5-HT1D alpha or 5-HT1D beta) has been tried with ketanserin which has an at least 60 times higher affinity for 5-HT1D alpha (pki = 7.1) than 5-HT1D beta receptors. Since ketanserin (0.32 microM) did not affect the concentration-response curve for 5-carboxamidotryptamine (5-CT), the presynaptic 5-HT autoreceptor may belong to the 5-HT1D beta rather than the 5-HT1D alpha subtype. The sympathetic nerve terminals of the human saphenous vein are endowed with inhibitory 5-HT1D beta heteroreceptors, as indicated by the potency ratio of several 5-HT receptor agonists in inhibiting noradrenaline release in strips of this blood vessels and by the ability of methiothepin, but not of ketanserin 0.3 microM, to act as an antagonist. Noradrenergic nerves in the dura mater, which probably innervate its microvasculature, may also be endowed with inhibitory 5-HT receptors, since 5-HT inhibited noradrenaline release from this tissue. In strips of atrial appendages, 5-HT receptor agonists (e.g. 5-HT, 5-CT and sumatriptan) inhibited noradrenaline release at potencies which are correlated with their ki values at 5-HT1D alpha and 5-HT1D beta receptors. Since this inhibitory effect was antagonized by ketanserin (0.3 but not 0.03 microM) and methiothepin, the presynaptic 5-HT receptor in this tissue may belong to the 5-HT1D alpha subtype. However, this conclusion needs further confirmation by experiments with more potent and subtype-selective antagonists of 5-HT1D alpha and 5-HT1D beta receptors.

1. Spirally cut strips of the human saphenous vein and pulmonary artery were used to determine the pharmacological properties of the presynaptic prostanoid receptors involved in the modulation of sympathetic [3H]-noradrenaline release. Strips preincubated with [3H]-noradenaline were superfused with physiological salt solution containing inhibitors of uptake1 and uptake2 and rauwolscine to eliminate involvement of presynaptic alpha 2-adrenoceptors. Tritium overflow was evoked by transmural electrical stimulation (standard frequency: 2 Hz). 2. In the saphenous vein, prostaglandin E2 (PGE2) inhibited the electrically-evoked tritium overflow; at the highest concentration investigated, tritium overflow was inhibited by more than 75% and the pEC50 value was 7.00. These effects were mimicked by prostaglandin E1, the EP1/EP3 receptor agonist, sulprostone and the EP2/EP3 receptor agonist, misoprostol with the rank order (pEC50): sulprostone (8.60) > PGE1 (7.25) > misoprostol (6.96). This rank order of potency suggests that the inhibitory effect of the drugs is mediated by presynaptic EP3-receptors. In contrast, PGF2 alpha did not inhibit evoked tritium overflow; the IP/EP1 receptor agonist iloprost and the stable thromboxane A2 analogue U 46619 (9, 11-dideoxy-11 alpha,9 alpha-epoxy-methanoprostaglandin F2 alpha) produced inhibition only at concentrations above 1 microM. 3. The EP1-receptor antagonist, AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) had no effect on the evoked tritium overflow nor did it modify the inhibitory effect of PGE2, further excluding involvement of inhibitory presynaptic EP1-receptors. 4. PGD2 caused a facilitation of evoked tritium overflow in the saphenous vein; this facilitation is probably mediated by presynaptic DP-receptors, since it was abolished by the selective DP-receptor antagonist, BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethylamino)hydantoin).5. In the pulmonary artery, sulprostone (pECm value 8.35), misoprostol (7.70) and PGE2 (6.80)inhibited electrically-evoked tritium overflow. This rank order of potency is consistent with the involvement of inhibitory presynaptic EP3-receptors.6. These results suggest that the sympathetic nerve fibres of both human saphenous vein and pulmonary artery are endowed with presynaptic inhibitory EP3 receptors. The EP3-receptors do not interact with the alpha 2-autoreceptors. In addition, the human saphenous vein seems to be endowed with presynaptic facilitatory DP-receptors.

19 patients in whom cardiopulmonary bypass (cpb) was performed during different types of cardiac operations, developed myocardial failure which remained refractory to inotropic support with increasing doses of adrenaline, dopamine and dobutamine, so that it was impossible to discontinue cpb. After changing the therapeutic approach to a new regime consisting of adrenaline, dopamine and enoximone, low-output syndrome (LCOS) could be successfully reversed in 12 of the 19 patients. In the 7 remaining patients blood pressure dropped in a clinically relevant way under treatment with enoximone. 5 of these patients needed intraaortic balloon pumping (IABP) inspite of the application of enoximone, before cpb could be successfully discontinued. In three patients receiving enoximone, persisting ventricular tachyarrhythmia appeared under treatment, and disappeared after discontinuation of the drug. One patient needed IABP and left heart bypass by means of the centrifugal pump before cpb could be duly discontinued. One patient died intraoperatively due to untreatable right ventricular failure and inability to discontinue cpb. It is concluded that enoximone represents a useful drug in a significant number of patients developing heart failure refractory to inotropic support, on emerging from cpb during cardiac surgery.

Forty-two patients (6 women, 36 men; mean age 55 [39-69] years), with one-, two- or three-vessel disease on coronary angiography, were studied using single-photon emission computer tomography with 15-p-123I-iodophenyl-pentadecanoic acid (IPPA), in order to evaluate this new method of demonstrating abnormalities of myocardial perfusion. The reference range for fatty acid turnover was determined in eleven controls (4 women, 7 men; mean age 41 [20-51] years) with no coronary stenosis. 185 MBq (5 mCi) of IPPA was administered intravenously during submaximal stress on a bicycle ergometer. Comparison between different regions of the tomograms revealed changes in fatty acid utilization typical of ischaemia. The sensitivity, specificity and predictive value of a positive result compared with coronary angiography were 95%, 89% and 93%, respectively, for the area supplied by the anterior interventricular artery, 92%, 91% and 93% for the circumflex branch and 89%, 91% and 90% for the right coronary artery. In 25 out of 31 patients (81%) with myocardial infarction, IPPA scintigraphy infarct localization agreed with the clinical findings. In two cases with unremarkable scintigrams left ventriculography showed hypokinesia, while in four cases neither method demonstrated any abnormality. There was one false-positive scintigram. IPPA scintigraphy has greater sensitivity and specificity than conventional nuclear medicine techniques in the demonstration of coronary heart disease.

A total of 29 patients with coronary artery disease (CAD) were investigated with 15-(p-[123I] iodophenyl)pentadecanoic acid (123I-IPPA) and sequential single photon emission tomography (SPET). Of these, 19 were studied after aorto-coronary bypass graft surgery. Some 13 patients without evidence of CAD served as a control group. Two SPET studies (early and late) were carried out within 45 min after intravenous administration of 200 MBq 123I-IPPA at peak sub-maximal exercise. Semi-quantification of uptake (related to perfusion) and turnover (linked to metabolism) was obtained by segmental comparison of oblique slices. Taking coronary arteriography as the "gold standard", 123I-IPPA scintigraphy had the following figures of merit for sensitivity and specificity in the diagnosis of CAD: for the left anterior descending artery territory 93% and 95%, for the left circumflex artery region 96% and 92%, and for the right coronary artery territory 77% and 92%, respectively. In all, 90% of the reperfused myocardial segments showed an improvement of uptake. Of these, 61% exhibited increased turnover after revascularization and 39% had pathologic turnover and thus a dissociation of improvement of perfusion and oxidative metabolism after surgery.

A high frequency ultrasound system processor was used for an intraoperative evaluation of coronary blood flow velocity and volume. In 12 patients with symptomatic coronary heart disease, morphology and hemodynamic parameters of the coronary artery system were examined intraoperatively. Optimal imaging was possible by keeping the ultrasound transducer at a constant distance of a few millimeters from the surface of the heart and the pericardial space between them filled with saline solution. Using this technique, large areas of the cardiovascular system were reproducible up to a peripheral vascular diameter of 2-3 mm. Blood flow velocity (20 to 33 cm/s) and blood volumes (33 to 94 ml/min) provide quantitative information on the degree of stenosis intraoperatively after coronary anastomosis during bypass surgery. All images were of outstanding quality and precision. This method is highly valuable for the intraoperative determination of blood flow parameters.