Identification of presynaptic beta 2-adrenoceptors on the sympathetic nerve fibres of the human pulmonary artery.

Strips of human pulmonary arteries from patients undergoing surgery for lung tumour were incubated with [3H]-noradrenaline. Subsequently, they were superfused with physiological salt solution containing cocaine and corticosterone. Tritium overflow from the strips was stimulated by transmural electrical impulses (2 Hz). The electrically evoked overflow of tritium consisted of 91% unmetabolized [3H]-noradrenaline, and this percentage was not altered by isoprenaline. Adrenaline (in the presence of rauwolscine), isoprenaline and the preferential beta 2-adrenoceptor agonist, procaterol, concentration-dependently increased the electrically evoked tritium overflow. Prenalterol, a beta-adrenoceptor agonist with moderate preference for beta 1-adrenoceptors, was considerably less active than the previously mentioned agonists; noradrenaline (in the presence of rauwolscine) was ineffective. The concentration-response curve of procaterol was shifted to the right by the preferential beta 2-adrenoceptor antagonist ICI 118-551 but was not affected by the beta 1-selective antagonist, atenolol. Propranolol, but not atenolol, produced a shift to the right of the concentration-response curve of isoprenaline. It is concluded that the sympathetic nerve fibres of the human pulmonary artery are endowed with facilitatory presynaptic beta 2-adrenoceptors.

Modulation of noradrenaline release in human saphenous vein via presynaptic alpha 2-adrenoceptors.

Strips of human saphenous veins were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing cocaine, corticosterone and propranolol. The electrically (6 Hz) evoked overflow of tritium (78% of which was accounted for by unmetabolized [3H]noradrenaline) was abolished by tetrodotoxin or omission of Ca2+ from the superfusion fluid. Unlabelled noradrenaline, alpha-methylnoradrenaline, B-HT 920 and clonidine inhibited the evoked overflow (maximum effect of clonidine lower than that of the other compounds) whereas methoxamine was ineffective. The alpha 2-adrenoceptor antagonists, BDF 6143 and rauwolscine, facilitated the evoked overflow but no effect was obtained with prazosin. Rauwolscine produced a shift to the right of the concentration-response curve of B-HT 920 for its inhibitory effect on evoked outflow and BDF 6143 caused a shift to the right of the corresponding curve of clonidine. It is concluded that the stimulation-evoked release of noradrenaline from the sympathetic nerve fibres of the human saphenous vein is modulated via presynaptic alpha 2-adrenoceptors.

Role of cAMP for regulation of impulse-evoked noradrenaline release from the rabbit pulmonary artery and its possible relationship to presynaptic ACTH receptors.

Strips of the rabbit pulmonary artery preincubated with 3H-noradrenaline were superfused with physiological salt solution containing cocaine, corticosterone and propranolol. Basal tritium efflux and electrically evoked tritium overflow were determined. The basal efflux of tritium was not affected by forskolin 0.01-10 mumol/l, 8-Br-cAMP and dibutyryl-cAMP 10-330 mumol/l, or the phosphodiesterase inhibitors rolipram 1-10 mumol/l and AH 21-132 l mumol/l; it was increased by AH 21-132 10-100 mumol/l. Forskolin concentration-dependently increased the evoked 3H overflow, and this effect was not attenuated by omission of cocaine. The facilitatory effect of forskolin was more pronounced at 0.66 Hz than at 2 Hz. Rolipram, AH 21-132, 8-Br-cAMP or dibutyryl-cAMP also produced a concentration-dependent increase in evoked 3H overflow (8-Br-cAMP was more effective than dibutyryl-cAMP in this respect). Except for the highest concentration investigated, AH 21-132 was more effective in facilitating evoked overflow than in increasing basal efflux. Forskolin, AH 21-132 or 8-Br-cAMP did not alter the percentages of 3H-noradrenaline and 3H-metabolites contained in basal tritium efflux or in stimulation-evoked tritium overflow. When a combination of AH 21-132 plus 8-Br-cAMP or AH 21-132 plus forskolin was administered, the facilitatory effect on evoked tritium overflow was more pronounced than with the single compounds alone. ACTH1-24 also facilitated the evoked tritium overflow. Combined exposure to ACTH1-24 plus forskolin, ACTH1-24 plus AH 21-132 or ACTH1-24 plus forskolin plus AH 21-132 resulted in a clearly more pronounced increase in evoked tritium overflow than exposure to the single compounds alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of cAMP in modulation of noradrenaline release in the human pulmonary artery.

After incubation with 3H-noradrenaline, strips of human pulmonary arteries from patients undergoing surgery for lung tumour were superfused with physiological salt solution containing cocaine and corticosterone. Forskolin, AH 21-132 (a cAMP phosphodiesterase inhibitor), 8-Br-cAMP and isoprenaline did not affect the basal tritium efflux from the strips, but produced a concentration-dependent facilitation of the tritium overflow evoked by transmural electrical stimulation (2 Hz). The facilitatory effect of isoprenaline was potentiated by forskolin which produced a shift to the left of the concentration-response curve of isoprenaline. It is concluded that cAMP plays a role in the modulation of noradrenaline release in the human pulmonary artery and that presynaptic beta-adrenoceptors appear to be coupled to an adenylate cyclase in the sympathetic nerve terminals.

Pharmacological characterization of the imidazoline receptor which mediates inhibition of noradrenaline release in the rabbit pulmonary artery.

Imidazoline receptors involved in modulation of noradrenaline release were characterized in the rabbit pulmonary artery preincubated with [3H]noradrenaline and superfused with physiological salt solution containing cocaine, corticosterone and propranolol. Tritium overflow was evoked by transmural electrical stimulation. The alpha 2-adrenoceptor blocking imidazolines tolazoline, BDF 6100 [2-(2-imidazoline-2-ylamino)-isoindoline] and BDF 7572 (4,7-dichloro-derivative of BDF 6100) increased the electrically evoked 3H overflow; the concentration-response curves were bell-shaped. In contrast, two other imidazolines, i.e. moxonidine and clonidine, two guanidine derivatives structurally related to BDF 6100, i.e. aganodine and BDF 7579 [4-chloro(2-isoindolinyl)-guanidine], as well as the catecholamine noradrenaline concentration-dependently inhibited the evoked 3H overflow. The concentration-response curves for moxonidine, clonidine, aganodine, BDF 7579 and noradrenaline were shifted to the right by rauwolscine. The apparent pA2 value of rauwolscine against moxonidine was 8.22, whereas those against clonidine, aganodine, BDF 7579 and noradrenaline were in the range of 6.37-6.77 and, hence, considerably lower than reported for alpha 2-adrenoceptors. In the presence of rauwolscine an inhibitory effect was also observed with the alpha 2-adrenoceptor blocking imidazolines tolazoline, BDF 6100, BDF 7572, and the imidazoline ST 587 [2-(2-chloro-5-trifluoromethylphenylimino)-imidazoline]; the rank order of potency of all guanidines and imidazolines investigated was: aganodine greater than BDF 7579 greater than BDF 7572 greater than BDF 6100 greater than clonidine greater than ST 587 greater than moxonidine greater than tolazoline.(ABSTRACT TRUNCATED AT 250 WORDS)

Facilitatory presynaptic angiotensin receptors on the sympathetic nerves of the human saphenous vein and pulmonary artery. Potential involvement in beta-adrenoceptor-mediated facilitation of noradrenaline release.

Spirally cut strips of human saphenous vein and pulmonary artery preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and desipramine or cocaine. In the saphenous vein angiotensin I, angiotensin II and angiotensin III concentration-dependently increased the electrically (2 Hz) evoked tritium overflow (relative order of potency: angiotensin II greater than angiotensin I greater than angiotensin III). The angiotensin receptor antagonist saralasin displaced the concentration-response curve of angiotensin II to the right, and also blocked the facilitatory effect of angiotensin III. Captopril, an inhibitor of angiotensin converting enzyme, did not modify the concentration-response curve of angiotensin I and did not significantly diminish the release-increasing effect of the nonselective beta-adrenoceptor agonist isoprenaline, whereas saralasin attenuated the facilitatory effect of the beta 2-adrenoceptor agonist procaterol. In the pulmonary artery the angiotensin receptor agonist Val5-angiotensin II-Asp1-beta-amide also increased the electrically evoked tritium overflow in a concentration-dependent manner. It is concluded that the sympathetic nerve fibres of the human saphenous vein (and probably of the human pulmonary artery as well) are endowed with facilitatory presynaptic angiotensin receptors. Angiotensin I exerted its facilitatory effect in the saphenous vein probably via direct stimulation of angiotensin receptors but not by conversion to angiotensin II. Furthermore, the beta 2-adrenoceptor-induced facilitation of noradrenaline release may in part be mediated by local stimulation of angiotensin II synthesis, which may occur by increased formation or activation of renin and/or increased availability of angiotensinogen.

Effective doses to patients from paediatric cardiac catheterization.

The Council Directive of the European Communities 97/43/Euratom requires dose assessment, especially for X-ray examinations of children and if high doses to the patient are involved. Both these aspects apply in cardiac catheterization and angiocardiography of children. Effective doses are a good indicator of radiation risk, particularly for leukaemia. Effective doses have been determined for 2114 infants and children undergoing cardiac catheterization from 1984 to 1996 at the University Hospital in Essen. Conversion factors (effective dose/dose-area product) were calculated based on direct dose-area product measurements for posteroanterior (PA) and lateral (Lat) projections as well as on patient records and examination details. The factors are calculated for eight age groups of children, taking into account the X-ray tube voltage for fluoroscopy and cine-film sequences, with and without zoom mode. Frequency distributions are presented for 2114 patients, for dose-area product, number of angiographic examinations (each combined with one cine-film sequence both PA and Lat) and for calculated effective doses. Highest effective doses are found in newborns (18.0 mSv and 6.5 mSv 90th and 50th percentiles, respectively) compared with adolescents of 15-21 years (8.0 mSv and 3.0 mSv 90th and 50th percentiles, respectively). Effective dose for cardiac catheterization is highest for newborns, in spite of lowest measured dose-area products, because the decreased value of the conversion factors overcompensates for the increase of dose-area product with age. This is especially important because of the higher tumour risk for equal effective dose for young children compared with adults.

Further evidence for the involvement of cyclic AMP in Ca2+-dependent, but not Ca2+-independent, noradrenaline release in the rabbit pulmonary artery.

Strips of the rabbit pulmonary artery were incubated with 3H-noradrenaline and subsequently superfused. In strips superfused with Ca2+-free solution containing K+ 64.7 mmol/l, tritium overflow was stimulated by introduction of Ca2+ 1.6 mmol/l; in strips superfused with physiological salt solution, stimulation was carried out with veratridine 30 mumol/l, acetylcholine 1 mmol/l (in the presence of atropine 1 mumol/l) or tyramine 100 mumol/l. The Ca2+-, veratridine- or acetylcholine-induced tritium overflow was facilitated by forskolin, AH 21-132 (a cAMP phosphodiesterase inhibitor) and/or 8-Br-cAMP, i.e. compounds which increase intraneuronal cAMP content. In contrast, the Ca2+-independent tyramine-evoked tritium overflow was not affected by these drugs. It is concluded that cAMP is involved in the regulation of stimulation-evoked Ca2+-dependent noradrenaline release, and that the sympathetic nerve terminals are endowed with an adenylate cyclase system. Facilitation of release may be caused by an alteration of Ca2+ influx or utilization.

[Persistent truncus arteriosus communis (type I) and interruption of the aortic arch (type B) (author's transl)]. / Persistierender Truncus art. communis (Typ I) und unterbrochener Aortenbogen (Typ B).

Description of the history, the clinical findings, and the autoptic results in a 5-days-old newborn child with a truncus arteriosus (Type I) and an interrupted aortic arch (Type B). Perfusion of the distal aortic arch by a wide open Ductus arteriosus. Additional anomalies: Atrial septal defect with partial anomalous pulmonary venous drainage of the right lung into the right atrium. Persistant left superior vena cava which leads to the left atrium. Hypoplasia and dysplasia of the left kidney. A tear caused by friction in the left sensorium with intra-and subdural bleeding. Discussion of the clinical, electrocardiographic, radiologic, angiocardiographic and pathologic-anatomical peculiarities of the persistent Truncus arteriosus and of the interrupted aortic arch connected with both defects.

[Recent viewpoints on the examination and therapy of infants and children with congenital cardiovascular defects]. / Neuere Gesichtspunkte bei der Untersuchung und Behandlung von Säuglingen und Kindern mit angeborenen Herz- und Gefässanomalien.

Basic methods for the examination including echocardiography are described. Indications for cardiac catheterization, angiography, and a description of the risk of these invasive methods are given. Cardiac catheterisation is necessary as early as possible in all cyanotic infants who are suspected to have heart defects - even in newborns. In transposition of the great arteries the hemodynamics can be improved by balloon septostomy during the first days of life. After septostomy the children can be operated upon during the second half of the first year of life. Non-cyanotic infants with an uncertain diagnosis or recurrent or medically not treatable heart failure have to be examined to clarify the need for an operation. Generally, early operative correction during the first year of life is the best, even more so with unsuccessful - medical treatment. This is valid especially for children with ventricular septal defects, although up to 60% of them tend to close spontaneously. Early correction almost always prevents obstructive pulmonary vascular disease. In contrast in aortic stenosis, cases for operative treatment should be carefully selected. Only critical stenoses have to be operated on very early. To choose the right time for operation and thereby save the childrens life it is necessary to be sure of an intensive and continuous follow-up by a pediatric cardiologist in all children with congenital heart disease.

Noradrenaline release in the human pulmonary artery is modulated by presynaptic alpha 2-adrenoceptors.

We used strips of human pulmonary arteries from patients undergoing surgery for lung tumor to investigate whether or not this human tissue (like that of the rabbit) is endowed with inhibitory presynaptic alpha 2-adrenoceptors. The strips were incubated with [3H]noradrenaline and subsequently superfused with physiological salt solution containing cocaine, corticosterone, and propranolol. The electrically (2 Hz) evoked overflow of tritium consisted of 89% unmetabolized [3H]noradrenaline and was abolished by tetrodotoxin or omission of Ca2+ from the superfusion fluid. Unlabeled noradrenaline, adrenaline, and the preferential alpha 2-adrenoceptor agonists B-HT 920, alpha-methylnoradrenaline, and clonidine concentration dependently inhibited the evoked overflow (maximum effect of clonidine lower than that of the other compounds): the alpha 1-selective agonist methoxamine was ineffective. The alpha 2-adrenoceptor antagonists BDF 6143 and rauwolscine facilitated the evoked overflow; the alpha 1-selective antagonist prazosin was ineffective. The concentration-response curve of B-HT 920 for its inhibitory effect on evoked overflow was shifted to the right by rauwolscine. It is concluded that the sympathetic nerve fibres of the human pulmonary artery possess presynaptic alpha 2-adrenoceptors. Stimulation-evoked release of noradrenaline is inhibited by activation and facilitated by blockade of these receptors.

[The QT syndrome in newborn infants]. / Das QT-Syndrom bei Neugeborenen.

The QT-syndrome-the hereditary prolongation of the QT-interval with or without concomitant deafness--may cause ventricular tachycardia or fibrillation and is therefore a life-threatening disease. The prognosis, however, can be considerably improved by a therapy with beta-blockers. For this reason, neonates of affected families should undergo cardiologic examination. It is essential to establish the diagnosis as early as possible and to start a prophylactic therapy immediately.

[Unilateral proximal aplasia of the pulmonary artery--studies on the clinical significance and embryologic interpretation]. / Einseitige proximale Aplasie der Pulmonalarterie--Untersuchungen zur klinischen Bedeutung und embryologischen Deutung.

Description and discussion of the findings in a five month old infant and a six year old boy, in whom unilateral absence of the pulmonary artery contralateral to the aortic arch could be demonstrated by means of angiocardiography. The infant, having absence of the right pulmonary artery associated with patent ductus arteriosus and obstructive pulmonary vascular disease of the left lung died after recurrent pulmonary infections in acute heart failure. The boy with absence of the left pulmonary artery could be shown to have moderate-severe peripheral stenosis at the origin of the right pulmonary artery from the main pulmonary artery. Pulmonary function studies showed normal values. During a follow-up of 5 years the boy doesn't show any symptoms. In both cases an accessory vessel could be demonstrated on the side of the absent pulmonary artery originating from the innominate artery and leading to the hilum of the corresponding lung. Embryologically these vessels probably represent persistence of the second primitive ductus arteriosus. According to its development the disease more precisely should be designated as unilateral proximal aplasia of the 6th ventral aortic arch, i.e. of the definitive pulmonary artery.

[Diagnosis and differential diagnosis of heart tumors in infancy and childhood]. / Diagnostik und Differentialdiagnose der Herztumoren im Säuglings- und Kindesalter.

The clinical features of 10 children, in whom the diagnosis of a cardiac tumor has been made, are reviewed. There were nonspecific systolic murmurs in 9 patients, depression of the S-T segment in the ECG of 7 children, and premature extrasystoles or supraventricular tachycardia in 4 children. X-ray always showed mild to moderate enlargement of the heart, but an abnormal contour could be detected only in 2 of the patients. While findings of cardiac catheterization were unspecific, the diagnosis could be made angiographically in 8 cases. Invasive studies, however, are now only indicated, if a proper diagnosis cannot be made by means of echocardiography. The diagnosis should be suspected in children with a nonspecific murmur, cardiomegaly and ECG-changes. Usually the diagnosis of a cardiac tumor is an indication for operation.

Studies on the fine structure of corynebacterium diphtheriae-granules.

The seemingly homogeneous metachromatic and electron-scattering granules of Corynebacterium diphtheriae have two structural components as revealed under conditions of low beam load and by use of ribonuclease. They contain high percentages of P and Ca. Findings point to participation of ribosomes and intracytoplasmic membranes in the formation of the granules.

[Risks in heart catheterization and angiocardiography in infancy and childhood]. / Risiko der Herzkatheterisierung und Angiokardiographie im Säuglings- und Kindesalter.

The results of cardiac catheterization with or without angiocardiography in 689 infants and 1311 children and adolescents were reviewed. In the first week of life 14,81% of the patients died within or after 24 hours of the procedure, 7,41% in the first month of life, 2,78% in the first year. And on the whole the mortality was 0,95%. Four expired after the first month of life and none after the fourth. All those infants who expired were in poor general condition with severe cyanosis and congestive heart failure.

[Echocardiographic studies in children with chronic kidney insufficiency and intermittent hemodialysis treatment]. / Echokardiographische Untersuchungen bei Kindern mit chronischer Niereninsuffizienz und intermittierender Hämodialysebehandlung.

Cardiac function was measured in 10 children (mean age 12 years) undergoing chronic intermittent hemodialysis. Blood pressure, heart rate and body weight were checked three times before and after hemodialysis. Echocardiographic studies were performed according to the references of the American society of echocardiography. 6 patients were normotensive, 4 patients hypertensive. Cardiac function was normal before and after hemodialysis in all patients. Ultrafiltration reduced body weight on average by 1.2 kg. The mean systolic blood pressure remained unchanged, the mean diastolic blood pressure declined in normotensive patients from 66 mm Hg to 53 mm Hg and in hypertensive patients from 100 to 85 mm Hg on average; the systolic leftventricular diameter (LVES) was reduced by dialysis from 2.7 to 2.3 cm, the enddiastolic leftventricular diameter (LVED) from 4.42 to 4.02. Cardiac output declined from 62.04 ml to 56.68 ml/min, whereas heart rate, shortening fraction and mean circumferential fiber-shortening-time increased. In normotensive patients LVED shortened more (4.4 to 3.86 cm) than in hypertensive children (4.44 to cardiac output 4.18 cm), but there were no significant differences. Significantly decreased only in the normotensive children. In hypertensive children the shortening fraction increased significantly (35.54 to 42.48%) in contrast to normotensive children (40.84 to 38.44%). Cardiac preload (LVES) and (LVED) and afterload (diastolic pressure) was reduced significantly after volume elimination. These changes in cardiac function suggest, that cardiac alterations found before hemodialysis are only functional and not structural.

Partial replacement of the left ventricular wall for a large intramural fibroma.

A case of successful operative treatment of an intramural fibroma of the left ventricular posterior wall is presented. Symptomatology, diagnosis, and a surgical procedure based on ventricular replacement using a doubled Dacron patch, fixed in "sandwich" technique, are discussed. It is possible to resect and replace large parts of the ventricular wall because of the well-developed compensatory capacity of the remaining unaffected myocardium in children.

[Changes in blood pressure in children with valvular aortic stenosis in bicycle ergometer stress]. / Blutdruckveränderungen bei Kindern mit valvulärer Aortenstenose unter fahrradergometrischer Belastung.

Children with aortic stenosis (n = 25) show a lower systolic blood pressure elevation during exercise than normal subjects (n = 47). The post-exercise systolic blood pressure minus the pre-exercise systolic pressure was calculated in both groups (23.60 +/- 10.8 mm Hg versus 47.23 +/- 14.9 mm Hg). There is no significant correlation between pressure response during exercise and the pull back gradient during heart catheterization. But if the difference between post-exercise systolic pressure and pre-exercise pressure is greater than 25 mm Hg there is a very low probability of a pull back gradient greater than 50 mm Hg. We conclude that exercise testing may be helpful in selecting those patients with aortic stenosis for catheterization who are likely to require surgery.