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Biomedical subjects

S Golf

Publications and source records attributed to S Golf.

54 records · Page 3Linked to original sources
PubMed1986

Effects of beta blocking agents on the density of beta adrenoceptors and adenylate cyclase response in human myocardium: intrinsic sympathomimetic activity favours receptor upregulation.

The density of beta adrenoceptors, the relative number of beta 1 and beta 2 adrenoceptor subtypes, and adenylate cyclase activity were studied in preparations from atrial biopsy specimens of 32 patients with coronary heart disease. Six patients were not receiving beta blocking agents, whereas the others were treated with different beta blocking drugs (timolol, propranolol, pindolol, metoprolol, and atenolol). Clinical and haemodynamic variables were similar in the different groups of patients. Beta adrenoceptor density was 17% significantly lower in the non-treated group than in the groups treated with beta blocking drugs. Among these, the group treated with pindolol, a drug with intrinsic sympathomimetic activity, had receptor densities that were 38% significantly higher than those treated with other beta blocking drugs and 51% significantly higher than the non-treated group. The relative numbers of beta 1 and beta 2 adrenoceptor subtypes were very similar in the different groups (beta 1 receptors 75-80%, beta 2 receptors 20-25%). A significant increase in the ratios of terbutaline stimulated to basal and terbutaline stimulated to isoproterenol stimulated adenylate cyclase activities was found in patients treated with beta 1 selective blockers (metoprolol, atenolol), indicating that beta 1 selective drugs may improve beta 2 receptor-adenylate cyclase coupling. In contrast, pindolol caused a significant reduction in the ratio of terbutaline stimulated to isoproterenol stimulated adenylate cyclase activity, indicating that this drug may cause a reduction in beta 2 receptor-adenylate cyclase coupling efficacy. Thus treatment with beta blocking agents causes upregulation of human myocardial beta receptor density. Intrinsic sympathomimetic activity seems to favour receptor upregulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1986

Congenital swallowing-induced symptomatic heart block: a case report of a probably hereditary disorder.

A 15-year-old girl had had syncope induced by swallowing since infancy. An ECG recorded during food intake revealed SA block with very slow junctional and ventricular escape rhythms. No symptoms or signs of other cardiac disorders or gastrointestinal diseases were present. Activation of a strong vagal reflex, able to inhibit impulse formation and propagation in an otherwise normal heart, is the most likely explanation of the disorder in this patient. Furthermore, ECGs of her close relatives which were recorded during food intake as compared with the findings in a reference group (n = 20), indicated that a genetic factor could be involved.

Adolescent↗
PubMed1986

Relative potencies of various beta-adrenoceptor antagonists (BAA) at the level of the human myocardial beta-adrenoceptor-adenylate cyclase (AC) complex. Is intrinsic sympathomimetic activity (ISA) due to AC activation?

Nine different beta-adrenoceptor antagonists (BAA), five with intrinsic sympathomimetic activity (ISA), were examined for their ability to inhibit isoproterenol-stimulated adenylate cyclase (AC) activity and specific 125I-cyanopindolol (CYP) binding in crude membrane particles from human myocardium. The BAA's were: propranolol, pindolol, timolol, alprenolol, metoprolol, atenolol, prenalterol, ICI 141.292 'Visacor', and ICI 118.587 'Corwin'. Whether BAAs with strong ISA were able to stimulate AC activity by themselves were examined in separate experiments and compared to the AC stimulation by full agonists. All the BAAs caused a concentration dependent, and at high doses apparently complete, inhibition of both isoproterenol-stimulated AC activity and 125I-CYP binding. Both assays made possible a 'potency-ranking' of the different BAAs (pindolol greater than or equal to propranolol and timolol greater than ICI 142.292 and alprenolol greater than ICI 118.587, prenalterol and metoprolol greater than atenolol). Corrected IC50-values, derived from inhibition curves with both techniques, show that receptor binding and inhibition of receptor function follow each other closely. Prenalterol caused a very weak AC activation (5.4% of maximum), whereas the 'ISA-blockers', pindolol, ICI 141.292, and ICI 118.587 were unable to stimulate AC activity at concentrations which completely displaced 125I-CYP binding. In comparison, norepinephrine stimulated AC activity to the same level as isoproterenol (three to four times basal activity) and the beta 2-selective agonist terbutaline caused some 50% of maximal AC stimulation. This raises the question whether ISA is due to AC activation. The effect upon AC activation and 125I-CYP binding of drugs with beta-selectivity shows that both beta 1- and beta 2-receptors are coupled to the AC.

Adenylyl Cyclases↗
PubMed1985

Catecholamine-responsive adenylate cyclase activity in human endomyocardial biopsies. Individual sensitivity to isoproterenol stimulation and propranolol inhibition.

In the present study we have examined adenylate cyclase (AC) activity, the stimulation by isoproterenol and inhibition by propranolol, in endomyocardial biopsies from eleven patients with suspected cardiomyopathy. Biopsies were obtained by heart catheterization from the right endomyocardial surface of the interventricular septum. Three biopsies were taken from each patient (mean weight, 2.1 mg; range, 1.2-4.0 mg). One biopsy was studied by light microscopy. The two other biopsies were homogenized and AC activity in the homogenates was determined in the presence of different concentrations of isoproterenol and isoproterenol (5 micrograms/ml) combined with different concentrations of propranolol. Thus stimulation and inhibition curves were established for a pair of biopsies from each patient. Appropriate biopsy material was obtained in triplicate from only seven patients. In these patients the variance in maximal receptor stimulation (by isoproterenol) and inhibition (by propranolol) was significantly smaller in pairs of biopsies compared to the variance between all biopsies (p values from less than 0.05 to less than 0.025). Hence it is possible to determine AC activity, and adrenergic receptor function, in very small endomyocardial biopsies. New diagnostic possibilities could thereby be introduced.

Adenylyl Cyclases↗
PubMed1985

Beta-adrenoceptor density and relative number of beta-adrenoceptor subtypes in biopsies from human right atrial, left ventricular, and right ventricular myocard.

In the present study we estimated the relative number of beta-adrenoceptors in membrane preparations from right atrial and left ventricular biopsies from 8 patients, as well as from right ventricular biopsy from one patient. Determinations of relative number of beta adrenoceptor subtypes (beta1, beta2) were also performed. Estimations were performed in a radioligand assay, measuring specific binding of [125I]-cyanopindolol (CYP). Inhibition of specific [125I] CYP binding was studied by adding propranolol (non-selective antagonist), atenolol (beta1 selective antagonist) and ICI 118551 (beta2 selective antagonist) to the preparations. Some individual variance in total number of receptors was found. Per mg protein, the number of binding sites were higher in atrial preparations (mean 71.4 +/- 14.4 fmol X mg-1) than in left ventricular preparations (mean 30.2 +/- 7.1 fmol X mg-1). Receptor number in the right ventricular preparation was 49.5 +/- 2.6 fmol X mg-1. Approximately 25% of beta adrenoceptors were of beta2 subtype in preparations from both right atrial and left ventricular biopsies, as well as from the right ventricular biopsy. Thus, there are regional differences in the quantity of beta adrenoceptors in human myocard whereas the relative proportion of beta1 and beta2 receptors appears to be fairly constant.

Biopsy↗
PubMed1985

Hypertrophic cardiomyopathy characterised by beta-adrenoceptor density, relative amount of beta-adrenoceptor subtypes and adenylate cyclase activity.

The total quantity of beta-adrenoceptors and the relative amount of beta 1 and beta 2 receptor subtypes were determined in heart biopsies of 10 patients with various heart diseases and 5 patients suffering from hypertrophic cardiomyopathy (HOCM). In membrane particle preparations from the same patients we also examined the activity of the adenylate cyclase (AC), and its response to isoprenaline, terbutaline, histamine and sodium fluoride (NaF). The high affinity ligand [125I] (1)-cyanopindolol (CYP) was used in the binding assays, and the highly beta 2-selective antagonist ICI 118 551 for the determination of beta-adrenoceptor subtypes. No differences were found in total beta-adrenoceptor density between patients with HOCM and "controls" (27.6 +/- 14.2 vs 26.5 +/- 10.7 fmol . mg-1 protein). The relative amounts of beta 1 and beta 2 receptor subtypes were similar, patients with HOCM had 82.1 +/- 4.9% of beta 1 and 14.4 +/- 3.9% of the beta 2 receptor subtype, compared with 76.3 +/- 11.5% of beta 1 and 20.7 +/- 11.0% of the beta 2 subtype in the "control" patients. Both absolute activity of AC (pmol . mg-1 protein . min) as well as the relative responses to the various stimulators were not significantly different between the two groups. Thus, this study does not support the hypothesis that HOCM is a disorder with altered beta-adrenoceptor number or adenylate cyclase response to adrenergic agonists. Furthermore, HOCM is not associated with altered response of the AC system to histamine or NaF.

Adenylyl Cyclases↗
PubMed1984

Catecholamine responsive adenylate cyclase in human myocardial preparations. Properties and optimalization of assay conditions.

In the present study we have investigated the conditions for optimal adenylate cyclase (AC) activity in preparations of human myocardial biopsies, with emphasis on both basal enzyme activity and isoproterenol response. Different preparation procedures (homogenates, membrane particles) of the same biopsy showed no difference in relative response to isoproterenol, although absolute activities, using protein concentration for normalization, showed some variance. The AC-receptor complexes of the preparations were also stable when stored on ice for 3 h, and both basal and stimulated AC activities were constant at a wide range of protein concentrations (2.9-31.9 micrograms/tube), and throughout 92 min incubation. The effects of varying Mg2+, guanyl nucleotides (GTP, GMP-P(NH)P), and ATP concentrations on myocardial AC activities were also investigated under both basal conditions as well as after isoproterenol stimulation. The apparent Km for the substrate (Mg X ATP) binding to the AC was approximately 0.1 mmol/l. Isoproterenol stimulated the AC activity by increasing Vmax (41 to 142 pmol/mg protein X min) without any change in the apparent Km. Maximal relative activation by isoproterenol was achieved at pH 6.5-7.0. The concentration of isoproterenol causing half maximal AC stimulation was approximately 0.1 micrograms/ml (2 X 10(-4) mmol/l). Half maximal inhibition of isoproterenol (4 micrograms/ml) stimulated AC activity was obtained by 0.025 micrograms/ml propranolol (8 X 10(-5) mmol/l). The sensitivity and precision of this assay should make it possible to measure AC activity as well as isoproterenol response in very small quantities of myocardial tissue. This could provide a method for studying receptor functions of sick hearts by endomyocardial biopsies.

Adenosine Triphosphate↗
PubMed1983

Effect of hydration state on cardiac function in patients on chronic haemodialysis.

Haemodynamic studies were performed at rest and during exercise in five chronic haemodialysis patients at two different states of hydration, called "normal hydration" and "over-hydration" (mean change in body weight 2.9 kg). Apart from an increase in mean aortic pressure and cardiac index there were no signs of cardiac dysfunction at rest at normal hydration. On exercise the mean pulmonary artery and wedge pressure increased significantly while cardiac output doubled. Overhydration caused considerable increases in right and left sided heart pressures at rest, without any increase in cardiac index. These changes became more pronounced during exercise. Anaemia and arteriovenous shunting make dialysis patients very sensitive to volume load. Extreme anaemia should be avoided, and keeping dialysis patients in a state of low volume load should be given high priority.

Adult↗
PubMed1977

Swallowing syncope. A case report.

A previously healthy man complained of syncopes and convulsions during meals. Despite thorough gastroenterologic, neurologic and cardiologic examination, the condition was misinterpreted as a psychiatric disorder for 13 years. Then ambulatory ECG, using a casette recorder, revealed periods of 2nd degree AV block during swalllowing. Pacemaker implantation prevented the attacks.

Ambulatory Care↗
PubMedDate not supplied

Perioperative myocardial injury in patients undergoing aortic valve replacement.

In cases of myocardial hypertrophy myocardial protection may be insufficient. In order to determine the factors responsible for myocardial injury we assessed myocardial injury in 54 patients undergoing isolated aortic valve replacement. In all cases hypothermic cardioplegic arrest was induced. At 13 different times we measured the serum level of creatine-kinase (CK), myocardial bound creatine-kinase (CKmb), lactic dehydrogenase (LDH), alpha-hydroxybutyrate dehydrogenase (alpha-HBDH), glutamic oxaloacetic transferase (GOT) and myoglobin. The mean duration of ischemia was 52.6 +/- 16.2 minutes and the mean time of extracorporeal circulation was 85.85 +/- 20.25 minutes. By performance of a multiple regression analysis a significant correlation between ischemia and LDH and alpha-HBDH was found; CK, GOT, LDH and alpha-HBDH correlated with duration of extracorporeal circulation. In none of the patients was a low cardiac output syndrome observed. From our results we conclude that in our study myocardial protection was sufficient and therefore the detrimental effects of extracorporeal circulation were the determining factors of enzyme release.

Adult↗
PubMedDate not supplied

Intra-aortic balloon pumping support in surgically treated valvular heart disease: prognostic factors and survival.

Prognostic factors of Low Output Syndrome (LOS) requiring operative circulatory support by intra-aortic balloon-pumping (IABP) counterpulsation, were analysed in a population of 841 patients who underwent heart valve replacement surgery between June 1977 and May 1985. The incidence of IABP circulatory support was 6.8%. Mean survival time of patients who needed IABP was 2.35 years +/- 0.425 vs 6.30 years +/- 0.103 for patients who didn't have this complication. A multivariate analysis using the logistic model was done to pinpoint factors predictive of IABP support. The prognostic factors were pre-operative functional class, presence of prior valve replacement, presence of concomitant surgery and presence of endocarditic etiology. The subgroup of 58 patients undergoing balloon counterpulsation was analysed for factors predictive of survival using a multivariate analysis of the Cox' model. Presence of aortic or mitral regurgitation was found to be the independent risk factor of mortality. Using a combination of prognostic factors, we pinpointed groups of patients at high risk of needing post-operative balloon pump counterpulsation support. The necessity of an alternative procedure for the mechanical support of the failing circulation is underlined.

Aortic Valve↗