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Biomedical subjects

E G Krause

Publications and source records attributed to E G Krause.

At least 55 records · Page 3Linked to original sources
PubMed1994

Titin, myosin light chains and C-protein in the developing and failing human heart.

We investigated relative amounts of titin, myosin light chains (MLC), C-protein, and myosin heavy chains (MHC) in the functionally intact contractile apparatus of embryonic, adult normal, and adult failing human left ventricle by SDS polyacrylamide gel electrophoresis and Western blot analysis. The amount of titin and the titin-MHC ratio was significantly (P < 0.05) lower in the embryonic and adult failing human compared to the adult normal fibres. Additionally, we found a protein band having a lower molecular weight but the same immunoreactivity as native titin (fast-migrating titin; FM-titin) in the failing heart only. The MLC-1/MLC-2 ratio was about 1.0 in normal and failing hearts but about 2.0 in the embryonic heart. Relative amount of C-protein was the same in normal and failing fibres but lower in the embryonic ventricles. Length-tension ratio of chemically skinned fibres prepared from terminally failing hearts was impaired compared to normal heart fibres. We conclude that both the reduced titin/MHC ratio and the expression of a structurally different titin form may be involved in the impaired contractile function of the terminally failing human heart.

Carrier Proteins↗
PubMed1994

Cardiac troponin I and tension generation of skinned fibres in the developing rat heart.

During development of the myocardium the troponin I (TNI) isoform expression is switched from a cAMP-insensitive, slow skeletal muscle TNI to a cAMP-sensitive, cardiac TNI isoform (cTNI). To study the functional consequence of alterations in cTNI expression in the rat heart we investigated the cAMP-controlled cTNI phosphorylation in comparison with alterations of functional properties of isolated cardiac myofibrils during the first postnatal month. cTNI was identified by Western blot analysis followed by a semiquantitative assessment. From the third to the 28th postnatal day the relative concentrations of the cardiac isoform of TNI increased 2.9 +/- 0.3-fold. In the same period the amount of phosphate incorporated into cTNI in the presence of exogenous cAMP-dependent protein kinase (PKA) and 32P[gamma]-ATP was increased 5.8 +/- 0.2-fold (24.2 +/- 3.5 v 140.2 +/- 7.6 pmolP/mg protein loaded onto the gel) whereas the phosphorylation of C-protein was only increased 1.6 +/- 0.2-fold. Ca(2+)-activated isometric tension generation of skinned heart fibres measured in the range of pCa from 6 to 4.5 was not affected by PKA at day 3. However, isometric tension generation of fibres prepared from 28-day-old rats was suppressed by incubation with PKA which was accompanied by a rightward shift in the force/pCa relation. Under these conditions half-maximal tension development was found at pCa 5.38 v 5.52 (p < 0.05) in the absence of PKA. The Ca2+ sensitivity of the contractile apparatus was not affected by PKA-induced phosphorylation of C-protein. These data give direct evidence for the physiological relevance of the onset of cAMP-induced phosphorylation of cTNI for the Ca(2+)-activated tension generation in cardiac myofibrils during postnatal development.

Animals↗
PubMed1994

Early release of glycogen phosphorylase in patients with unstable angina and transient ST-T alterations.

OBJECTIVE: To determine whether transient ST-T alterations in patients with unstable angina are associated with an increase in plasma glycogen phosphorylase BB concentrations on admission to hospital. DESIGN: Prospective screening of patients with unstable angina for markers of myocardial cell damage. SETTING: Accident and emergency department of university hospital. PATIENTS: 48 consecutive patients admitted for angina pectoris (18 with transient ST-T alterations). None of the patients had acute myocardial infarction according to standard criteria. MAIN OUTCOME MEASURES: Creatine kinase and creatine kinase MB activities, creatine kinase MB mass concentration, and myoglobin, cardiac troponin T, and glycogen phosphorylase BB concentrations on admission. RESULTS: All variables except for creatine kinase and creatine kinase MB activities were significantly higher on admission in patients with unstable angina and transient ST-T alterations than in patients without. However, glycogen phosphorylase BB concentration was the only marker that was significantly (p = 0.0001) increased above its discriminator value in most patients (16). In the 18 patients with transient ST-T alterations creatine kinase MB mass concentration and troponin T and myoglobin concentrations were significantly (p = 0.0001) less commonly increased on admission (in five, three, and two patients, respectively). CONCLUSIONS: The early release of glycogen phosphorylase BB may help to identify high risk patients with unstable angina even on admission to an emergency department. Glycogen phosphorylase BB concentrations could help to guide decisions about patient management.

Angina, Unstable↗
PubMed1994

Glycogen phosphorylase isoenzyme BB mass release after coronary artery bypass grafting.

Glycogen phosphorylase isoenzyme BB mass release was studied in 20 patients undergoing coronary artery bypass grafting. In 16 patients with uneventful coronary artery bypass grafting, glycogen phosphorylase isoenzyme BB mass concentrations showed a significant, transient increase in the post cross-clamping period and decreased to baseline values within 20 hours (peak concentrations ranged from 12.7 micrograms/l to 47.5 micrograms/l, median 40 micrograms/l). One patient did not fulfil criteria for perioperative myocardial infarction, but clinical data indicated myocardial injury after aortic unclamping. In this patient only glycogen phosphorylase isoenzyme BB mass concentration and not creatine kinase isoenzyme MB catalytic concentration was increased, compared with uneventful patients. In 2 patients with emergency coronary artery bypass grafting for evolving myocardial infarction, glycogen phosphorylase isoenzyme BB mass concentrations, but not creatine kinase isoenzyme MB catalytic concentrations, correlated with clinical evidence of myocardial ischaemia. Our data indicate that glycogen phosphorylase isoenzyme BB mass concentration is a very sensitive laboratory marker of perioperative myocardial injury in patients undergoing coronary artery bypass grafting.

Aged↗
PubMed1993

Phosphorylation of the L-type calcium channel beta subunit is involved in beta-adrenergic signal transduction in canine myocardium.

Cyclic AMP-mediated phosphorylation of calcium channel subunits was studied in vitro and in vivo in preparations from dog heart. Calcium channels in native cardiac membranes were phosphorylated by cAMP-dependent protein kinase (PKA) solubilized with digitonin and subsequently immunoprecipitated using a polyclonal antibody generated against the deduced carboxy-terminal sequence of the cardiac beta subunit. A 62 kDa protein was identified as the major PKA-substrate in the immunoprecipitates. In the intact myocardium, this putative beta subunit was found to be phosphorylated in response to cAMP elevating agents. In contrast, no phosphorylation of a protein with an electrophoretic mobility similar to the alpha 1 subunit was detected, although 1,4-dihydropyridine receptor sites were recovered in the immunoprecipitates. Thus, we suggest that PKA-mediated phosphorylation of the beta subunit is the major mechanism for beta-adrenergic regulation of cardiac L-type calcium channel activity.

Amino Acid Sequence↗
PubMed1993

Protein phosphorylation and cardiac function: cholinergic-adrenergic interaction.

OBJECTIVE: The muscarinic inhibition of cyclic AMP (cAMP) mediated contractile effects may not only be the result of a reduction in cAMP levels, but may also involve cAMP linked protein phosphorylation in the heart. To show that a cholinergic agonist may antagonise the effects of agents that induce the cAMP signalling sequence at the level of protein phosphorylation, the effect of carbachol was investigated on the in vivo phosphorylation of phospholamban, troponin I, and a 15 kDa protein during positive inotropic intervention with isoprenaline, forskolin, and a phosphodiesterase inhibitor in the isolated rat heart. METHODS: The contractile activity of the heart was monitored during drug administration, and the hearts were freeze clamped for assay of protein phosphorylation and metabolites [cAMP, cyclic guanosine monophosphase (cGMP), cAMP dependent protein kinase (cA-PK), and phosphorylase a]. For estimation of the amount of in vivo phosphorylation, a "back phosphorylation" method was used. RESULTS: Carbachol attenuated in vivo phosphorylation, induced by cAMP increasing drugs, of all the phosphoproteins studied, whereas the accumulation of cAMP was not affected or was decreased to 61% after exposure to isoprenaline alone. In addition, the cAMP mediated phosphorylase a activation was completely reversed by carbachol. similarly, sodium nitroprusside reduced phosphorylation as well as the contractile force of the investigated phosphoproteins. CONCLUSIONS: These data confirm the reduction of cAMP mediated cardiac protein phosphorylation by carbachol. The cholinergic antagonism may primarily involve cellular target systems distal to sites of cAMP generation. The observed similarity in the cardiac response to carbachol and sodium nitroprusside indicates a role of cGMP in the antiadrenergic action of carbachol in the myocardium.

Animals↗
PubMed1993

Protein phosphorylation in the regulation of cardiac contractility and vascular smooth muscle tone.

This review discusses phosphorylation of target proteins in the plasma membrane, the sarcoplasmic reticulum, and the myofilaments of cardiac and vascular smooth muscle cells known to be important in regulating contraction and relaxation. Substantial data have been obtained on the regulation of calcium uptake mechanisms of the sarcoplasmic reticulum in cardiac as well as vascular smooth muscle, suggesting a central role of phospholamban for relaxation in the cardiovascular system. As shown for cardiac muscle, the calcium release from the sarcoplasmic reticulum is also under beta-adrenergic control via phosphorylation of the ryanodine receptor. The developmental switching from the skeletal to the cardiac isoform of the cardiac thin-filament protein troponin I marks the onset of beta-adrenergic regulation of myofilaments through phosphorylation. Further examples for the genetic control of systems regulated by protein phosphorylation are presented. The review emphasizes the power of molecular-biologic approaches in combination with traditional methods to achieve significant progress in this field of cardiovascular research.

Animals↗
PubMed1992

[Potential cardiotonics. 14. Synthesis and in vitro positive inotropic actions of 4-morpholino-5-(4-pyridinyl)pyridine derivatives].

By the reaction of 2-chloro-5-(4-pyridinyl)pyridines 1-6 with morpholine as well as by derivation of the 2-morpholino-pyridine-3-carboxamide 8 the 3-substituted 2-morpholino-5-(4-pyridinyl)pyridines 7-14 were prepared. The evaluation for positive inotropic properties in spontaneously beating isolated guinea pig atria gave for the 3-cyano derivative 7 (AWD 122-14) the best activity. The potency is comparable to that of milrinone and is due to partial by inhibition of phosphodiesterase III (PDE III).

Animals↗
PubMed1991

[Cellular and molecular mechanisms in heart failure].

In patients with heart failure there are distinct functional abnormalities in the myocytes themselves. This review deals with the deteriorations in the myocardial energy metabolism and the recently found alterations in the neurohumoral and hormonal signal transduction and signal realization within the cardiac cells. Beside the reduction in the volume of mitochondria in the overloaded myocardium the energy starvation is also reflected by a decrease in the content of high energy phosphates. Studies on nonfailing and failing human ventricular myocardium identified significant alterations in the neurohumoral regulation of the heart including the fluxes and the transport processes of Ca2+ as well as the beta-adrenoceptors, G-proteins, cAMP levels and cAMP-mediated processes. Recent data on the existence of auto-antibodies against the ADP/ATP translocator of the mitochondrial membrane and of stimulatory acting autoantibodies against i) the L-type calcium channel and ii) the beta 1-adrenoceptor, respectively, in patients with dilated cardiomyopathy, may open a new view in the etiology of heart failure and for consequences in the therapeutic concept of these diseases.

Autoantibodies↗
PubMed1990

Differential sensitivity to isoprenaline of troponin I and phospholamban phosphorylation in isolated rat hearts.

Phosphorylation of phospholamban (PLB), a membrane-bound 15 kDa protein and troponin I (TNI) was studied in isolated perfused rat hearts by using the back-phosphorylation technique with [32P]ATP catalysed by an excess of exogenous catalytic subunit of cyclic AMP (cAMP)-dependent protein kinase, followed by protein separation. This standardized method allows the quantitative detection of protein phosphorylation specifically stimulated by cAMP. In control hearts the extent of specific phosphorylation was equivalent to 3.3 nmol of PLB and 11.0 mumol of TNI per g of cardiac tissue. In hearts freeze-clamped 30 s after exposure to isoprenaline (10 pM-10 microM), there was a dose-dependent decrease in phosphate incorporation in vitro, indicating a phosphorylation of the respective proteins in vivo. A differential sensitivity of TNI and PLB phosphorylation towards the beta-adrenergic agonist and the subsequent increase in tissue cAMP was found, favouring TNI phosphorylation. K0.5 values for isoprenaline were 2.94 +/- 0.04 nM and 4.46 +/- 0.24 nM for PLB and the 15 kDa protein, but 0.13 +/- 0.01 nM for TNI phosphorylation in the intact tissue. At an isoprenaline-induced increase in cAMP less than 3 pmol/mg of protein there was no or only a small increase in PLB phosphorylation, whereas TNI phosphorylation was nearly maximal. By plotting phosphorylation data against changes in contractile parameters a strong correlation was obtained for TNI (r = 0.95), assuming a linear relationship. For PLB a complex relationship is likely to exist. Our data (i) indicate a functional compartmentalization of the cAMP signal cascade and (ii) confirm that phosphorylation of TNI rather than of PLB is related to changes in mechanical myocardial responses.

Adenosine Triphosphate↗
PubMed1990

Perioperative assessment of cardiac energy metabolism by means of arterio-coronary venous difference in lactate concentration (acDL). A parameter for optimizing ventricular function of the postcardioplegic myocardium.

Fourty-three patients undergoing open heart surgery were subjected to extended hemodynamic and metabolic monitoring (arterial and coronary sinus (CS) lactate concentration). In 95% of patients investigated, a significant increase in CS lactate concentration above the arterial lactate concentration was established at the beginning of reperfusion (RPT). In these cases, a decrease in the CS lactate below the arterial concentration occurs within the RPT creating a cross-over point (COP) from negative to positive lactate extraction values. Whereas the initial rise in CS lactate is an expression of the expected ischemia-induced acceleration of anaerobic glycolysis, the onset of a positive lactate extraction can be related to reconsolidation of mitrochondrial oxidative phosphorylation. We found two groups with an early and late COP at 7.2 +/- 0.8 min (ECOP) and 42.5 +/- 5.2 min (LCOP) (P less than 0.005). Whereas a short cross-over time was associated with a normal postoperative outcome, cardiac recovery was delayed in the LCOP group. With the aid of metabolic monitoring it is possible to identify the COP and cardiac overload situations and so to optimize the perioperative outcome, especially in selected patients (NYHA stage III/IV, re-operation, high-risk operation).

Adenosine Triphosphate↗
PubMed1990

[Heart surgery interventions in risk patients. New possibilities for improving therapeutic results].

Perioperative therapy in conjunction with cardiac surgery had so far been guided by functional, paraclinical, and clinical parameters which only conditionally enabled objective appraisal of the present condition of the myocardium. Perioperative recording of the arterio-coronary-venous concentration difference of lactate (acDL) has now enabled the use of an objectivated parameter for accurate description of the metabolic-energetic situation of the myocardium. This will be helpful in metabolic-energetic condition monitoring (MESM) to optimise perioperative cardiotonic therapy. Stabilisation of the metabolic-energetic situation of the myocardium, objectivated by MESM, has proved to be superior to premature cardiac support, using catecholamines. It has been associated with improved restitution with high significance (p less than 0.005).

Adult↗
PubMed1990

[Base activity of glycogen phosphorylase b in human serum. Study of reference and discrimination values].

Serum glycogen phosphorylase activity as one of the sensitive indicators for the diagnosis of acute heart infarction was determined at 216 healthy probands using a standardized fluorometric procedure with a detection range from 0.03 to 6 nmol/s x l serum. Basal activity was averaged at 1.22 +/- 0.39 nmol/s x l serum with a confidence interval of C.I.95 1.168 ... 1.272. Due to the estimated Gaussian distribution of the individual activity values (n = 216) the reference range was calculated from 0.5 to 2.0 nkat/l (2.5- to 97.5-percentile, respectively), the latter one being equal to the reference value of the glycogen phosphorylase activity in healthy human beings. The reference value was found to be independent of age (16-65 years) and sex. Using the discrimination value for serum glycogen phosphorylase activity at 3 nkat/l serum two groups of patients suffering either from acute myocardial infarction (n = 79) or chronic ischemic heart disease (n = 92) were separated with a diagnostic sensitivity and specificity of 0.91 and 0.93, respectively, of this diagnostic tool.

Adolescent↗
PubMed1989

Transient changes in cyclic AMP and in the enzymic activity of protein kinase and phosphorylase during the cardiac cycle in the canine myocardium and the effect of propranolol.

Oscillation of cyclic AMP and in the activity ratio of cyclic AMP-dependent protein kinase and of glycogen phosphorylase with the cardiac cycle were demonstrated in the canine heart in situ. For tissue sampling an ECG (R-wave)-triggered, automatically working push-freeze-drill apparatus was developed which allows intraventricular cryobiopsies from the left ventricular muscle of anaesthetized open-chest dogs. The nucleotide cyclic AMP oscillated with the cardiac cycle during normal working condition, the higher cyclic AMP level occuring during systole. Cyclic GMP was assayed to be without oscillatory changes during the contraction-relaxation cycle. The rise in the activity ratio of protein kinase was found to coincide with the maximum in the level of cyclic AMP. Propranolol pretreatment prevents the transient in the level of the nucleotide as well as in the activity ratio of the kinase indicating i) a causal relationship between these changes and ii) a neurohumoral, beat-to-beat regulation by catecholamines released from the sympathetic nerve endings within the heart. Contrary the activity ratio of phosphorylase retains its transient changes during the cardiac cycle in the presence of propranolol, indicating a Ca-mediated activation of phosphorlase kinase during the contraction process.

1-Propanol↗
PubMed1989

PGE1 and iloprost affect the high energy phosphates in the global ischemic and reperfused rat heart: a 31P-NMR study.

The influence of PGE1, iloprost and a combination of both on high energy phosphate levels in isolated rat hearts reperfused 1 h following 20 min of global ischemia was investigated employing 31P-NMR-spectroscopy. Whereas PGE1 induced a slight reduction in the decline of the creatine phosphate/inorganic phosphate. ATP/inorganic phosphate ratio and NMR-energetic index during ischemia, iloprost application was followed predominantly by a temporary but marked improvement of the creatine phosphate/inorganic phosphate ratio during the early period of reperfusion. The best results in preservation of high energy phosphates were achieved after simultaneous application of PGE1 and iloprost. It is presumed that the accelerated normalization of the heart function observed immediately after ischemia in the eicosanoid treated hearts is related to the more rapid recovery of intracardial high energy phosphate level.

Adenosine Triphosphate↗