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Biomedical subjects

W Schmitz

Publications and source records attributed to W Schmitz.

At least 181 records · Page 10Linked to original sources

Evidence against a role of a pertussis toxin-sensitive guanine nucleotide-binding protein in the alpha 1-adrenoceptor-mediated positive inotropic effect in the heart.

Pertussis toxin, which specifically inactivates guanine nucleotide-binding proteins (N-proteins) involved in the signal transduction in various receptor systems, did not influence the positive inotropic effect of the alpha 1-adrenoceptor agonist phenylephrine in rat isolated left auricles. This indicates that the alpha 1-adrenoceptor-mediated positive inotropic effect does not involve a pertussis toxin-sensitive N-protein.

Animals↗

[Resumption of employment following aortocoronary bypass operation].

Between April 1981 and May 1983, 921 patients with coronary sclerosis underwent a bypass operation. Following the operation, 327 of these patients were asked to give their professional status. These were compared with the surgical result and the clinical findings. During the 22-month follow-up period 47.1% were without work. 52.9% returned to work after an average of 3.3 months. The following factors played a significant role in the decision whether or not to return to work: 1) the age of the patient (p less than 0.001); 2) the degree of physical stress to which the patient was subjected in his job before the operation (p less than 0.001); 3) the severity of the postoperative angina pectoris symptoms (p less than 0.01); 4) the improvement in the output of the left ventricle (p less than 0.05) and 5) the participation in rehabilitation treatment (p less than 0.01). By reducing the preliminary investigation period, increasing the operation capacity and making more effective use of the rehabilitation programme, more people could return to work after the operation and this in turn would increase our patients' quality of life.

Angina Pectoris↗

Increased responsiveness to stimulation of alpha- but not beta-adrenoceptors in the hereditary cardiomyopathy of the Syrian hamster. Intact adenosine- and cholinoceptor-mediated isoprenaline antagonistic effect.

The effects of phenylephrine (in the presence of propranolol) or isoprenaline and of adenosine or carbachol (alone and in the presence of isoprenaline) were studied on the force of contraction in electrically driven papillary muscles isolated from the hearts of cardiomyopathic (strain BIO 8262) and age-matched, healthy Syrian hamsters. All experiments were performed in the so-called prenecrotic stage of the disorder within the first 30 days of life. Phenylephrine exerted a positive inotropic effect in all preparations from the cardiomyopathic hamsters. In contrast, in thirteen preparations from healthy Syrian hamsters, phenylephrine increased force of contraction in only four preparations. The positive inotropic effect of isoprenaline was similar in both cardiomyopathic and healthy Syrian hamsters. Adenosine and carbachol apparently reduced the isoprenaline-induced increase in force of contraction in both cardiomyopathic and healthy Syrian hamsters. We conclude that an increased responsiveness to alpha-adrenergic stimulation occurs in the hearts of cardiomyopathic Syrian hamsters and may be related to the myocardial injury occurring in this syndrome. An increased responsiveness to beta-adrenoceptor stimulation or an impaired adenosine-mediated or cholinoceptor-mediated feedback inhibition is unlikely to play a role in the aetiology of this syndrome.

Adrenergic alpha-Agonists↗

Role of guanine nucleotide-binding protein in the regulation by adenosine of cardiac potassium conductance and force of contraction. Evaluation with pertussis toxin.

In atrial cardiac preparations adenosine exerts a receptor-mediated negative inotropic effect due to an increased potassium conductance. Pretreatment of guinea pigs with pertussis toxin abolished the negative inotropic and action potential shortening effect of adenosine and the adenosine analogue (-)-N6-phenylisopropyladenosine (PIA). As pertussis toxin specifically inactivates guanine nucleotide-binding proteins involved in the signal transfer from receptor binding to specific cell functions, it is concluded that a guanine nucleotide-binding protein is involved in the regulation of the receptor-mediated change in potassium conductance and force of contraction.

Action Potentials↗

Increased sensitivity to alpha-adrenoceptor stimulation but intact purinergic and muscarinergic effects in prehypertensive cardiac hypertrophy of spontaneously hypertensive rats.

The effects of phenylephrine, isoprenaline and adenosine, (-)-N6-phenylisopropyladenosine (PIA) or carbachol alone and in the presence of isoprenaline on force of contraction were studied in isolated electrically driven papillary muscles of spontaneously hypertensive rats (SHR) and age-matched Wistar control rats. In SHR an increased heart to body weight ratio was observed when blood pressure was not yet elevated. During this stage of the syndrome (i.e. between the 27th and 35th day of life) phenylephrine was about 3.4 times more potent to increase force of contraction in SHR (mean EC50: 2.8 mumol l-1) than in control rats (mean EC50: 9.4 mumol l-1). The positive inotropic effect of isoprenaline was similar in SHR and control rats. Also no difference could be detected in the isoprenaline-antagonistic effect of adenosine, the adenosine receptor agonist PIA or carbachol. We conclude that an increased sensitivity to cardiac alpha-adrenoceptor stimulation might be related to prehypertensive cardiac hypertrophy in SHR.

Adenosine↗

[Indications for ligation of ductus arteriosus Botalli persistens in premature infants].

Ligation of patent ductus arteriosus can be safely performed even in the smallest prematures and may be life-saving. Medical treatment with prostaglandin-inhibitors may be substituted in selected cases. From 1976-1985 a total of 215 prematures was treated. 52 of those experienced spontaneous closure. In 68 infants closure occurred following indomethacin-treatment. 48 had operation after failure of medical therapy and 53 with contraindications to indomethacin were primarily operated. The overall mortality reached 20% and was highest among those with combined medical and surgical treatment.

Birth Weight↗

Ruptured aneurysms of the sinus of Valsalva.

From 1964 to 1984, 10 male and 5 female patients with ruptured aneurysms of the sinus of Valsalva (ASVs) underwent surgical correction. These procedures constituted 0.23% of the 6,350 surgical procedures that used cardiopulmonary bypass during this period. Five patients had an inflammatory condition (bacterial endocarditis, 4; syphilis, 1), and 1 had an ASV relapse 5 years after her first operation. Coexistent lesions included aortic valve regurgitation in 5 patients, ventricular septal defect in 3 (1 of whom had mitral insufficiency), patent foramen ovale in 2, and atrial septal defect in 1. Ninety-three percent were symptomatic (sudden onset of symptoms, 5 patients; gradual onset, 9 patients), commonly with shortness of breath, fatigability, chest pain, and tachycardia. The following connections occurred: noncoronary sinus to right atrium (RA) (5 patients); right coronary sinus (RCS) to RA (5 patients); and RCS to right ventricle (5 patients). There were no early or late postoperative deaths. One patient underwent reoperation after an ASV relapse. The mean follow-up period (+/- standard deviation) was 7.9 years (range, 10 months to 20.1 years). Eighty percent of the patients were found to be in New York Heart Association class I, and 20% were in class II. Apart from ASV relapse, late complications are determined by prosthetic valve dysfunction or evidence of valve disease. Early surgical intervention is justified in patients with ruptured ASV.

Adolescent↗

[Scanning electron microscopy image of the cells of the conjunctival epithelium in specimens from impression cytology].

Impression cytology specimens of the conjunctiva can be examined by scanning electron microscopy. If a cellulose-acetate filter is pressed onto the conjunctiva, the microvilli-bearing epithelium becomes so firmly attached to the fine meshwork of the filter that the most superficial conjunctival cell layers adhere to the filter. When the filter is removed intercellular connections are destroyed without any damage to the cell membranes being detectable in the SEM image. Since the surface of the corneal epithelium is spread out on the filter and is firmly attached to it the lateral bond between the cells is preserved. Shrinkage is minimal. The posterior surface of the epithelial cells, facing the observer, consists of smooth, porous cell membranes. The nuclei of many cells are clearly distinguishable. Since it can be directly compared with light-microscopic specimens, the SEM image can help provide answers to morphological and pathological questions, and may represent a useful diagnostic aid.

Adult↗

Does an impaired adenosine mediated feedback control play a role in the development of hereditary dystrophic cardiomyopathy?

A study was carried out to investigate whether or not an impairment of the adenosine mediated negative inotropic effect in the presence of beta adrenoceptor stimulation plays a role in the pathogenesis of the hereditary cardiomyopathy of the Syrian hamster. In electrically driven papillary muscles isolated from the hearts of cardiomyopathic (strain BIO 8262) and age matched healthy control Syrian hamsters the effects of isoprenaline, adenosine, and adenosine in the presence of isoprenaline were studied within the first 30 days of life (the prenecrotic stage of the disorder). In both cardiomyopathic and control hamsters adenosine antagonised the positive inotropic effect of isoprenaline, whereas adenosine alone had no or, only a weak, inhibitory effect on the force of contraction. The effects in both groups were similar. The effect of isoprenaline on the force of contraction also did not differ in the two groups. The data show that in both cardiomyopathic and control hamsters adenosine reduces the force of contraction during beta adrenergic stimulation. The potency or efficacy of adenosine did not differ in the two groups. An impaired adenosine mediated feedback control of the heart does not therefore seem to play a role in the pathogenesis of the hereditary dystrophic cardiomyopathy of the Syrian hamster.

Adenosine↗

Functional evidence for the existence of adenosine receptors in the human heart.

Adenosine added to isolated electrically driven preparations of human ventricular heart muscle antagonized the positive inotropic effect of isoprenaline (mean EC50 19 mumol 1(-1), n = 9). Similar effects were observed with the adenosine receptor agonist (-)-N6-phenylisopropyladenosine (mean EC50 0.5 mumol 1(-1), n = 7). These data provide functional evidence for the existence of adenosine receptors in the human myocardium which may modulate the force of contraction during beta-adrenergic stimulation and thus could be involved in the autoregulation of myocardial contractility.

Adenosine↗

Isoprenaline-like effects of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine on mechanical, biochemical and electrophysiological parameters in the mammalian heart.

The phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX) mimicked the effects of isoprenaline on the force of contraction, the cAMP content and the slow Ca++ inward current (Isi) in isolated guinea pig papillary muscles. The results support the hypothesis that phosphodiesterase inhibitors and beta-adrenoceptor agonists exert their positive inotropic effects by increasing Isi via the common mediator cAMP.

1-Methyl-3-isobutylxanthine↗

Effects of the beta 2-adrenoceptor agonists fenoterol and salbutamol on force of contraction in isolated human ventricular myocardium.

The effects of fenoterol and salbutamol on isometric force of contraction were studied in isolated, electrically driven human papillary muscle preparations. Fenoterol increased force of contraction at concentrations of 1 mumol l-1 and higher. The maximally effective concentration of fenoterol (100 mumol l-1) increased force of contraction by about 130%. The positive inotropic effect of fenoterol was not influenced by 0.1 mumol l-1 prazosin. The beta 1-selective antagonist atenolol (2 mumol l-1) and the beta 2-selective antagonist ICI 118551 (1 mumol l-1) shifted the concentration-response curve of fenoterol to the right, indicating that beta 1- and beta 2-adrenoceptors may contribute to the positive inotropic effect of fenoterol. In contrast to fenoterol, salbutamol increased force of contraction only by about 11% at 100 mumol l-1. The results indicate that: (1) fenoterol exerts a direct positive inotropic effect in the human heart which may support the beneficial effects of the reduction of systemic vascular resistance in patients with congestive heart failure; (2) this positive inotropic effect of fenoterol is mediated by beta 1- and beta 2-adrenoceptors; (3) the clinically observed improvement of cardiac performance in the case of salbutamol is presumably not due to any direct positive inotropic effect.

Adult↗

Positive inotropic effect of Bay K 8644: cAMP-independence and lack of inhibitory effect of adenosine.

The aim of the present study was to characterize the positive inotropic effect of the Ca2+ channel activator Bay K 8644. In isolated guinea-pig papillary muscles we investigated whether adenosine and the R site adenosine receptor agonist (-)-N6-phenylisopropyladenosine (PIA) were able to antagonize the positive inotropic effect of Bay K 8644. The effect of Bay K 8644 and adenosine or PIA on myocardial cAMP content was also measured. The influence of adenosine and PIA on the positive inotropic effect of the beta-adrenoceptor agonist isoprenaline and of the phosphodiesterase inhibitor amrinone was studied for comparison. Adenosine and PIA antagonized the positive inotropic effects of isoprenaline and amrinone in a concentration-dependent manner. In contrast, adenosine or PIA did not affect the positive inotropic effect of Bay K 8644. The positive inotropic effect of Bay K 8644 was not accompanied by a change in the cAMP content of the papillary muscles. Additionally applied adenosine or PIA also failed to affect the cAMP content. It is concluded that an increased myocardial cAMP content is not involved in the positive inotropic effect of Bay K 8644. Moreover, the results support the view that adenosine and PIA only antagonize the positive inotropic effects of drugs known to increase myocardial cAMP content and that an increased myocardial cAMP content is a prerequisite for the manifestation of a negative inotropic effect of the nucleosides in ventricular cardiac muscle.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗