[Open foramen ovale in patients with arterial vascular occlusions of the retina and optic nerve]. / Offenes Foramen ovale bei Patienten mit arteriellen Gefässverschlüssen der Netzhaut und des Sehnervs.

BACKGROUND: We examined the frequency and significance of persistent foramen ovale (PFO) in patients with ocular circulatory disturbance. PATIENTS AND METHODS: Forty patients with acute arterial occlusions of the posterior bulb segment were investigated by means of transthoracic and transesophageal echocardiography (TEE). The parallel presence of cerebral ischemia was clarified on the basis of existing CCT findings and by additional HMPAO-SPECT investigation. RESULTS: PFO was identified in nine of the patients investigated. The probability of paradoxical embolism arises from further findings: eight of those with PFO (89%) showed echocardiographic signs of right heart strain, indicating previous pulmonary embolism, compared with only three of those without PFO (10%). Five of those with PFO showed a potential source of embolism, two of them with phlebothromboses in their clinical history and three with additional atrial septal aneurysm. Cardiovascular risk factors were prevalent in the group without PFO. Both groups had a mean age of approximately 60 years. Signs of cerebral ischemia were present in the SPECT or CT findings for four of the patients with PFO and nine of those without. CONCLUSIONS: From our findings, it appears highly probable that ocular arterial occlusion is caused by paradoxical embolism. PFO should be taken into account in establishing a diagnosis, including diagnosis in elderly patients.

Acute influence of beta-adrenergic antagonists on left ventricular diastolic function: contrasting results after administration of celiprolol and metoprolol.

Various beta-adrenergic receptor antagonists have different effects on myocardial function. A clinical study was performed in 30 patients with symptomatic coronary artery disease and systemic hypertension to compare the effects of single intravenous doses of 0.15 mg/kg celiprolol (n = 16) (third generation beta-blocking agent) and metoprolol (n = 14) (second generation) on left ventricular diastolic function. Parameters derived from pressure, volume, flow, time intervals and their combination were used to characterise diastolic function. After celiprolol administration, parameters of diastolic myocardial function improve (dp/dtip-; relaxation time constant T1, peak filling rate PFR; first-third filling rate FF1/3 or diastolic wall stress-time integral Sigdiasc) or remain unchanged. In contrast, after metoprolol administration parameters of diastolic function seem to be deteriorated (dp/dtip-, T1; Sigdiasc). This indicates an improvement in myocardial relaxation and filling under the influence of celiprolol but not under metoprolol. The left shift of the pressure-volume loops after celiprolol (n = 13), in contrast to metoprolol, supports this interpretation. Celiprolol did not show any deterioration of diastolic function in patients with coronary heart disease and arterial hypertension under these acute conditions.

Celiprolol exerts microvascular dilatation by activation of beta 2-adrenoceptors.

In order to clarify the question whether the beta 1-selective adrenoceptor antagonist celiprolol possesses vasodilating properties, isolated vascular networks were perfused with increasing concentrations of celiprolol (in a cumulative manner) ranging from 10(-8) to 10(-4) mol/l. The study was carried out using the isolated mesenteric vascular bed of the guinea pig mesenterium coli. Vascular diameters of four different vascular regions [vessels classified as G1 (585 +/- 30 microns), G2 (403 +/- 25 microns), G3 (282 +/- 27 microns) and G4 (197 +/- 13 microns)] were assessed by means of microscopic videoangiometry. Perfusion with celiprolol resulted in concentration dependent vasodilation which was more pronounced in G3 and G4 vessels. In addition, cumulative concentration-response curves were determined from responses obtained in the presence of 10(-8), 10(-7), 10(-6) and 10(-4) mol/l ICI 118,551 (a highly selective adrenoceptor antagonist). In the presence of ICI 118,551 at concentrations greater than or equal to 10(-6) mol/l, no celiprolol response could be observed. Lower concentrations of ICI 118,551 shifted the celiprolol concentration-response curve to the right in a concentration-dependent manner. Therefore, it is concluded (a) that celiprolol has a vasodilating effect, (b) that this vasodilation is produced by stimulation of beta 2-adrenoceptors and (c) that the vasodilating effect is more pronounced in smaller than in larger vessels (G3, G4 vs G1, G2).

Distinct pathways for beta-adrenoceptor-induced up-regulation of muscarinic acetylcholine receptors and inhibitory G-protein alpha-subunits in chicken cardiomyocytes.

Exposure of cardiomyocytes from chicken embryos for 3 days to the beta-adrenoceptor agonist, isoproterenol, lead to a down-regulation of beta-adrenoceptors by about 70% and to a decrease in isoproterenol-stimulated adenylyl cyclase activity by about 40% (homologous desensitization). In addition, the isoproterenol treatment induced an increase in the level of muscarinic acetylcholine receptors by about 30% and an increase in pertussis toxin-catalyzed ADP-ribosylation of two about 40 kDa proteins, most probably alpha-subunits of the inhibitory G-protein (Gi), by about a factor of two (heterologous desensitization). The purpose of the present study was to characterize the role of beta-adrenoceptor-dependent and -independent mechanisms in heterologous desensitization of adenylyl cyclase. Therefore, the effect of pretreatment with the beta-adrenoceptor antagonist, propranolol, with the partial agonists, celiprolol and xamoterol, and with the beta-adrenoceptor-independent adenylyl cyclase activators, prostaglandin E1 and forskolin, on beta-adrenoceptors, muscarinic acetylcholine receptors and pertussis-toxin-catalyzed ADP-ribosylation of G-protein alpha-subunits was studied. Pretreatment of the cardiomyocytes for 3 days with xamoterol or celiprolol, but not with propranolol, induced a small decrease in beta-adrenoceptor number and in isoproterenol-stimulated adenylyl cyclase activity by about 15-20%. Exposure to prostaglandin E1 and forskolin lead to a more pronounced decrease in beta-adrenoceptor binding and in isoproterenol-mediated adenylyl cyclase stimulation by about 40-60% (heterologous desensitization). An increase in the level of muscarinic acetylcholine receptors, similar to that induced by isoproterenol exposure, was only observed after pretreatment with the partial agonists, celiprolol and xamoterol, but not after pretreatment with the beta-adrenoceptor-independent agonists, prostaglandin E1 and forskolin, nor after pretreatment with propranolol. In contrast, prostaglandin E1 and forskolin exposure lead to a similar increase in pertussis toxin-catalyzed ADP-ribosylation of about 40 kDa G-proteins as isoproterenol exposure whereas treatment with propranolol, celiprolol and xamoterol had no or only a very small effect on pertussis toxin substrates. In summary, the data suggest that, similar as shown for homologous desensitization, cyclic AMP-dependent and -independent mechanisms are also involved in heterologous desensitization of adenylyl cyclase stimulation. The beta-adrenoceptor-induced upregulation of muscarinic acetylcholine receptors and of the alpha-subunits of pertussis toxin-sensitive G-proteins, most probably of Gi, seem to be mediated via distinct pathways.

Acute haemodynamic profile of celiprolol in patients with coronary heart disease and hypertension: a double-blind comparison with metoprolol.

Celiprolol is a 'third generation' beta-blocking agent which is claimed to avoid problems associated with simpler beta-blockers, such as vasoconstriction, bronchoconstriction and myocardial depression. A double-blind randomized study was undertaken in 30 patients with coronary artery disease and hypertension to compare the haemodynamic effects of single intravenous doses of 0.15 mg kg-1 celiprolol (N = 16) and metoprolol (N = 14). Following celiprolol administration, the tendency was for myocardial function to improve or remain unchanged; left ventricular end-systolic volume and ejection fraction improved significantly (P less than 0.05). However, following metoprolol administration, the tendency was for myocardial function to deteriorate, with significant falls in cardiac output (P less than 0.05), ejection fraction (P less than 0.05) and velocity of circumferential shortening (P less than 0.01). There was a tendency for peripheral resistance to fall slightly with celiprolol but to rise markedly with metoprolol (pNS). Left ventricular pressure-volume loops showed improved performance with celiprolol and deterioration with metoprolol. Both drugs resulted in increases in coronary flow and myocardial oxygen consumption (P less than 0.05). Metoprolol, but not celiprolol, resulted in some deterioration in regional left ventricular wall motion (P less than 0.05). Celiprolol appears to be haemodynamically advantageous compared to metoprolol in patients with coronary artery disease and hypertension.

[Ultrastructural morphometric studies of the myocardium of cardiomyopathic hamsters of the BI0 8262 strain]. / Ultrastrukturell morphometrische Untersuchungen am Myocard cardiomyopathischer Hamster des Stammes BI0 8262.

Tissue of myocardium from (8262) hamsters, 2, 6 and 27 weeks of age, were analyzed with quantitative microscopic techniques. Besides alterations of some other structures, we found the most evident changes in the mitochondrial abnormalities exist at all ages. They may be related to defective energetic mechanism.

[Surgical therapy of bacterial endocarditis]. / Chirurgische Therapie der bakteriellen Endokarditis.

On the basis of an own clinical material of 26 patients and in comparison to the literature indications and results of the operative therapy in bacterial endocarditis were discussed. The progressive, conservatively not controllable cardiac insufficiency is the most frequent indication for operation. Without valve replacement it causes death in 60-90% of the patients. In contrast to this there is a postoperative early lethality of 10-30%. Among our own patients the early mortality was 19%. Ill patients operated on were in an advanced stage of the disease, seven patients had to be operated on under emergency conditions. Postoperatively, an improvement of the clinical stages by on an average two degrees of severity (NYHA) could be established. For the purpose of a further improvement of the changes of survival in patients with bacterial endocarditis the demands for an early diagnosis, an adequate antibiotic therapy, a well-timed operation and a suitable operating technique have to be fulfilled.

[Coronarography findings following systemic short-term lysis of acute myocardial infarct]. / Koronarographiebefunde nach systemischer Kurzzeitlyse des akuten Myokardinfarktes.

In 50 patients with acute infarction who were admitted within 6 hours after the beginning of the complaints randomizedly an intravenous streptokinase short-term lysis or a conventional heparin phenprocoumon treatment was performed and 4 weeks later the results were objectified by coronarography and ventriculography. The patients were subdivided into 3 groups: 1. control group (without fibrinolysis), 2. early lysis (within 4 hours) and 3. late lysis (4-6 hours). Four weeks after the infarction the proportions of the open infarction vessels are approximately of the same size in all three groups, the functional results are best (end-diastolic pressure and kinetics of the cardiac wall) in the group of patients who underwent an early lysis. Successfully lysed patients with remaining residual stenosis must be regarded as particularly threatened by infarction and remain under special control (residual angina, ergometrically objectified exercise tolerance, perhaps coronarography) in the phase of rehabilitation.

Epicardial image analysis using a desk top computer. Comparison of epicardial flow distribution and NADH-fluorescence pattern.

In isolated coronary-ligated rabbit hearts, quantification of epicardial flow distribution pattern and of ischemic area was performed from flow indicator and endogenous NADH-fluorescence pictures, respectively, after UV-flash photography. After being digitized (256 X 256 pixels), the fluorescence photos were analyzed by an Apple desk computer using self-written software (fast machine routines called from BASIC programs). The ischemic area (= sum of pixels with enhanced NADH fluorescence) corresponds to the area with disturbed coronary perfusion (= sum of pixels with diminished indicator fluorescence). Since coronary-active drugs might affect both parameters--local myocardial perfusion and metabolism--differentially, the method presented seems to be a very useful technique for differentiated analysis of the action profile of coronary-active drugs.

[ECG changes in the late postoperative course of patients following alloplastic heart valve replacement]. / Zur Bedeutung von Ekg-Veränderungen im späten postoperativen Verlauf bei Patienten nach alloplastischem Herzklappenersatz.

Based upon a total of 50 patients with alloplastic heart valve substitute an attempt was made to verify postoperative retrogression of the signs of hypertrophy in the ECG and to correlate them with the clinical findings. In accordance with the pertaining literature, the essential criterion for assessing left hypertrophy is the Sokolow index. In corrected aortic lesions there is a close relation between retrogression of electrocardiographic signs of hypertrophy and the clinical degree of severity. All patients with a retrogressive tendency of the signs of hypertrophy showed definite improvement of clinical findings. Patients in whom the ECG deteriorated did not have good clinical findings either. This clear relationship is not demonstrable in mitral lesions, since mitral stenosis and mitral insufficiency influence the left ventricle, the left atrium and the pulmonary circulation in various ways. A discussion of the assessment of the individual ECG symptoms and their causes is added.

[Upper gastrointestinal tract hemorrhages following heart surgery]. / Blutungen aus dem oberen Gastrointestinaltrakt bei herzoperierten Patienten.

The clinical histories of 612 patients who underwent an operation of the heart were evaluated. Eight times a more severe haemorrhage from the upper gastrointestinal tract was described, i.e. 1.3%. One patient died under the signs of the septic shock. All patients were treated conservatively, only in one patient an ulcer existed 12 years before the heart operation.

[Indication for alloplastic heart valve prosthesis]. / Indikation zum alloplastischen Herzklappenersatz.

The indication for the alloplastic substitution of the cardiac valve results from the expectation of life with natural course of the disease on the one hand and with the operative risk and late results on the other. For the diagnosis of heart diseases intracardial methods are necessary in much cases. Contraindications result from heavy myocardial and coronary changes which increase the operative risk considerably and no postoperative improvement is to be expected. In the low-pressure system the implantation of artificial cardiac valves is used cautiously and plastic methods are preferred.

[Catamnestic studies on the prodomal phase of myocardial infarct]. / Katamnestische Untersuchungen zur Prodromalphase des Myokardinfarktes.

In a retrospective study by means of a half-standardized method of interview in 154 patients with acute myocardial infarction and in a control group of the same age (n = 100) anamnestic data were established, particularly taking into consideration the preinfarction phase. 27% of the patients were surprised by an acute myocardial infarction without prodromal symptoms, in 32% the first occurrence of complaints of angina pectoris was during the last two months before the infarction. 41% had a preexisting angina pectoris which usually showed a crescendo-course with increasing approximation to the infarction. More than half of the patients reported on physical activity or/and emotional stress as causal factors of the preinfarction complaints. The correlation with the localisation of the infarction showed above all an occurrence of the prodromal symptoms in infarctions of the anterior wall and in lesions of the myocardium which in most cases could be ascertained only enzymatically. A greater accumulation of the prodromi was furthermore found in younger patients, in hypertension and preexisting restriction of the heart function. 70% of the patients with warning symptoms consulted a physician because of their heart complaints. In the control group 22% of the persons reported on heart complaints.